Vertebral Columns Fall 2021

INSIDE

Development of Alternative Anesthetic Techniques in Spine Surgery

Vertebral

COLUMNS International Society for the Advancement of Spine Surgery

Interfacet Spacers for Minimally Invasive Posterior Cervical Fusion: An Update on the Literature Minimally Invasive Surgical Approaches to Spine Deformity Live Cellular Allografts Platelet-Rich Plasma in Spinal Disorders

PLUS

THE CASE FOR AN

INTEGRATED SPINE SURGERY RESIDENCY

FA LL 2021

Minimally Invasive Techniques for Revision Lumbar Spine Surgery

Editor in Chief

3 6 12 16 19 23 27

Kern Singh, MD

EDITORIAL The Case for an Integrated Spine Surgery Residency

Peter Derman, MD, MBA

CLINICAL PRACTICE Minimally Invasive Techniques for Revision Lumbar Spine Surgery

MULTIMODAL ANALGESIA Development of Alternative Anesthetic Techniques in Spine Surgery

INSTRUMENTATION Interfacet Spacers for Minimally Invasive Posterior Cervical Fusion: An Update on the Literature

Brandon Hirsch, MD Sravisht Iyer, MD Yu-Po Lee, MD Sheeraz Qureshi, MD, MBA Managing Editor Audrey Lusher Designer CavedwellerStudio.com

DEFORMITIES Minimally Invasive Surgical Approaches to Spine Deformity

BIOLOGICS Live Cellular Allografts

PAIN MANAGEMENT Platelet-Rich Plasma in Spinal Disorders

Become a member today https://www.isass.org/about/membership/

Fall 2021

Editorial Board

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Vertebral Columns is published quarterly by the International Society for the Advancement of Spine Surgery. ©2021 ISASS. All rights reserved.

Opinions of authors and editors do not necessarily reflect positions taken by the Society.

This publication is available digitally at www.isass.org/news/vertebralcolumns-Fall-2021

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From Rush University Medical Center in Chicago, Illinois

EDITORIAL

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The Case for an Integrated Spine Surgery Residency Nisheka N. Vanjani, BS

Prior to the establishment of the specialized fields of neurosurgery and orthopedic surgery, spine surgeries were performed by general surgeons.1 During this period, only a handful of surgical techniques were employed, such as decompressions and laminectomies.1,2 Eventually, orthopedic and neurological procedures evolved from general surgery due to the high demand for operative repair of musculoskeletal and neurological injuries during World War I.2 Over the years, 2 training pathways have developed for spinal surgery specialization: (1) a 5-year orthopedic surgery residency followed by a mandatory spinal surgery fellowship and (2) a 7-year neurological surgery residency followed by an optional spinal surgery fellowship.2 With increased utilization of novel minimally invasive spine surgery techniques, robotic devices, and navigation technologies, the field of spinal surgery is ever evolving, facilitating better patient outcomes. 3 Nonetheless, to meet the needs of this complex subspecialty and to comprehensively train surgeons in these emerging techniques, more focused spinal surgery training must be provided. For this reason, in this article, we present the case for an integrated spinal surgery residency.

Since orthopedic surgery encompasses several subspecialties, most residency programs spend more time training surgeons on treating the most common musculoskeletal conditions, with lower resident case volume for complex subspecialties. 2 The lack of spine surgery case exposure in both orthopedic and neurological surgery residencies has been elucidated through the Accreditation Council for Graduate Medical Education (ACGME) resident case logs: among the total surgical cases performed by orthopedic and neurological surgery residents during a span of 10 years, only 4.9% and 31.3% were spinal surgeries, respectively.4 Despite the fact that these traditional training methods have produced highly skilled spinal surgeons, the majority of time spent in either of these programs remains undevoted to spine intervention. In addition, with the steep learning curve associated with mastery of both conventional spine procedures and emerging operative approaches and technologies,5,6 it may be inefficient to provide a limited spinal case load to trainees. Sclafani et al noted that most minimally invasive spine surgery techniques required around 20 to

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Madhav R. Patel, BS

Kevin C. Jacob, BS

Hanna Pawlowski, BS

Michael C. Prabhu, BS

Kern Singh, MD

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30 surgeries to minimize operative time and complications. 5 With the ultimate goal of optimizing patient outcomes, an integrated spinal surgery residency may offer surgeons the case load needed to overcome this learning curve prior to completion of their training.

Integrated procedural residencies have also been developed in other fields, including plastic, vascular, and cardiothoracic (CT) surgery. Bhadkamkar et al compared the evaluation of trainees in an integrated plastic surgery residency program vs an independent residency program (completion of a surgical residency and then another plastic surgery residency).7 The authors concluded that integrated residents performed better on their in-service examinations and were

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significantly less likely to fail their American Board of Plastic Surgery written examination.7 Similarly, Ward et al illustrated that compared with residents in non-integrated pathways, CT trainees in integrated programs had a much higher degree of thoracic operative exposure and additional nonsurgical rotations, enabling them to acquire skills not readily emphasized in traditional CT training programs.8 Results from established procedural integrated residencies may thus provide a case in support of an integrated training experience for spinal surgery.

Between neurosurgery and orthopedic surgery residency programs, there is a notable difference in spine surgery case volume, procedural hours, and fellowship attendance.4,9 Through a retrospective analysis of the AC-

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GME case logs, it was noted that neurosurgery residents performed around 6.8 times as many spinal surgery cases and logged 6.1 times as many spinal procedural hours when compared to orthopedic surgery residents.9 Alternatively, a greater number of orthopedic surgery residents pursue a spinal surgery fellowship, which may represent an avenue for orthopedic residents to achieve similar levels of spine surgical exposure. 9 Despite alternative training methods, surgeons who train in either of these residency programs have demonstrated similar perioperative and long-term patient outcomes.10 Nonetheless, there has been a lack of consensus among the two specialties in the methodologies utilized to treat certain spinal disorders.11 For example, Hussain et al discovered significant variation in the type of discectomy conducted, use of orthosis after fusion, and

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management of spondylolisthesis and spinal stenosis between neurological and orthopedic surgeons.11 Through an integrated residency, there would be a combination of techniques taught to residents, allowing for minimal discrepancy in surgical methodology.

The primary hesitations to an integrated residency pathway are the hyperspecialization of spinal surgeons and the cost of developing a new training program.12 While such limitations are important to consider, the opportunity for more longitudinal and comprehensive training, increased surgical volume, and collaborative and unified approaches to spinal operative care, an integrated spine surgery residency will likely provide substantial educational benefit and positive value to trainees, experienced surgeons, and, most importantly, patients. n

References 1. Zileli M, Sharif S, Fornari M, et al. History of spinal neurosurgery and spine societies. Neurospine. 2020;17(4):675-694.

2. Shaffrey CI, Buell TJ. Training the next generation of spine surgeons: an orthopedic and neurosurgical collaboration with historical precedence [editorial]. J Neurosurg Spine. Published online August 6, 2021. https://doi. org/10.3171/2020.12.SPINE201849 3. Kazemi N, Crew LK, Tredway TL. The future of spine surgery: new horizons in the treatment of spinal disorders. Surg Neurol Int. 2013;4(Suppl 1):S15-S21.

4. Pham MH, Jakoi AM, Wali AR, Lenke LG. Trends in spine surgery training during neurological and orthopedic surgery residency: a ten-year analysis of ACGME case log data. J Bone Joint Surg Am. 2019;101(22):e122.

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5. Sclafani JA, Kim CW. Complications associated with the initial learning curve of minimally invasive spine surgery: a systematic review. Clin Orthop Relat Res. 2014;472(6):1711-1717.

6. Joaquim AF, Vaccaro AR. Learning curve in spine surgery—too many techniques, too many options—how should young surgeons deal with this anxiety? Arquivos Brasileiros de Neurocirurgia: Brazilian Neurosurgery. 2019;38(01):040-041.

7. Bhadkamkar MA, Luu BC, Davis MJ, et al. Comparing independent and integrated plastic surgery residency models: a review of the literature. Plast Reconstr Surg Glob Open. 2020;8(7):e2897.

8. Ward ST, Smith D, Andrei A-C, et al. Comparison of cardiothoracic training curricula: integrated six-year versus traditional programs. Ann Thorac Surg. 2013;95(6):20512054; discussion 2054-2056.

9. Lad M, Gupta R, Para A, et al. An ACGME-based comparison of neurosurgical and orthopedic resident training in adult spine surgery via a case volume and hours-based analysis. J Neurosurg Spine.

Published online August 6, 2021. https:// doi.org/10.3171/2020.10.SPINE201066 10. Mabud T, Norden J, Veeravagu A, et al. Complications, readmissions, and revisions for spine procedures performed by orthopedic surgeons versus neurosurgeons: a retrospective, longitudinal study.

Clin Spine Surg. 2017;30(10):E1376-E1381.

11. Hussain M, Nasir S, Moed A, Murtaza G. Variations in practice patterns among neurosurgeons and orthopaedic surgeons in the management of spinal disorders.

Asian Spine J. 2011;5(4):208-212.

12. Albert TJ. Perspective on training future spine surgeons. Accessed October 16, 2021. https://www.spineuniverse. com/professional/news/perspective-training-future-spine-surgeons

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From the Hospital for Special Surgery in New York, New York

Minimally Invasive Techniques for Revision Lumbar Spine Surgery

Daniel Shinn, BS

Sidhant Dalal, BS

Sheeraz Qureshi, MD, MBA

Minimally invasive surgical (MIS) techniques employed in the contex t of lumbar spine surger y consistently demonstrate reduced morbidity, reduced postoperative pain, and improved postoperative recovery while retaining similar long-term functional outcomes as compared to analogous open techniques.1 Furthermore, MIS techniques are an increasingly prevalent choice for the primary treatment of degenerative lumbar pat holog y. 2 However, t he use of MIS techniques for revision lumbar spine surgery remains a relat ively nascent concept.

This article seeks to gather the available relevant literature to discuss the safety and potential advantages afforded by this approach to revisional procedures.

Additionally, we describe the various MIS revision procedures and how they are performed.

Potential Indications for the Need for MIS Revision In considering the many situations suitable for MIS revision, the scenario that most demonstrates the strengths of this concept would be the revision of a previous lumbar

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fusion. Typically fraught with danger, revision fusion may be performed either for pseudoarthrosis and hardware failure at an index level or extension of fusion for adjacent segment degeneration. This often involves dissection through extensive postoperative scar tissue and potentially involves the replacement of existing hardware. In a national registry study investigating more than 7,500 revision cases in patients undergoing lumbar spinal fusion, revision fusion was associated with increased rates of neurological complications, venous thromboembolism, wound infections, and unfavorable discharge disposition compared with primary fusions.3 Another smaller series of 47 revision lumbar fusion cases (either open posterolateral or circumferential fusion) demonstrated an 8.5% rate of severe intraoperative complications, including 3 iliac vein lacerations during anterior approach, while 10.6% had minor postoperative complications, including infections and new radiculopathy.4 Thus, MIS techniques pose the biggest potential benefit in this scenario as they provide less invasive methods of achieving fusion and avoidance of extensive posterior soft tissue dissection.

Lumbar Discectomy Low complication rates after MIS revision discectomy have been demonstrated in previous studies.5-9 In a systematic review of 37

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studies, revision MIS microdiscectomy resulted in lower complications compared with open revision discectomy.10 An additional comparison between open and MIS discectomy for recurrent disc herniation also demonstrated that both procedures had similarly low rates of incidental durotomy.8 In a study investigating patients undergoing MIS microdiscectomy for recurrent disc herniation, Albayrak et al demonstrated significant improvement in Oswestry Disability Index (ODI) scores in their cohort at not only 12 weeks postoperatively, but also at 7-year follow-up.9

Posterolateral Fusion & Posterior Lumbar Interbody Fusion In a previous series of patients undergoing open posterolateral fusion (PLF) after previous decompression surgery, the rate of major complication was low, including 4% incidence of intraoperative durotomy, 4% postoperative surgical site infection, and 2% reoperation for malpositioned hardware.11 Patients also demonstrated favorable improvement in ODI, visual analog scale (VAS) for back pain, and VAS for leg pain scores at 2 years postoperatively. A single-surgeon, retrospective study from 2008 compared the perioperative morbidity of 17 MIS lumbar interbody fusion revision surgeries to 26 primary surgeries.12 This study included only posterior lumbar interbody fusion (PLIF) and transforaminal lumbar interbody fusion (TLIF) patients, and the data suggested that although estimated blood loss and neurologic morbidity were similar, revision cases had higher rates of incidental durotomy and other perioperative complications. There are currently no studies

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that have directly compared open and MIS PLF/PLIF.

Transforaminal Lumbar Interbody Fusion With regards to open TLIF, primary cases and revision cases after previous decompression had a similar high rate of complications (32.8% vs 26.3%) in a series of 167 patients.13 Furthermore, patients with a history of 2 prior lumbar spine surgeries had increased rates of neural injuries and durotomies. Conversely, another study investigating MIS TLIF for revision after prior open discectomy in a series of 73 patients reported no major complications along with significant improvement in PROMs.14 In a previous study comparing MIS to open TLIF after previous lumbar decompression, MIS TLIF resulted in a much lower incidence of durotomy (12% vs 18.5%), less blood loss, and less postoperative back pain compared to open TLIF.15 In a comparison of endoscopic TLIF versus open PLF for adjacent segment disease (ASD), Ba et al16 demonstrated good clinical outcomes and no recurrences in either group of patients.

Additionally, the MIS technique resulted in less tissue trauma, improved cosmesis, and decreased blood loss and hospital length of stay compared to open lumbar fusion.16 Lateral Lumbar Interbody Fusion Choi et al17 studied 10 patients undergoing MIS lateral lumbar interbody fusion (LLIF) with percutaneous posterior instrumentation for rostral ASD above a previous posterolateral fusion. Three patients experienced transient thigh numbness and 1 patient had subjective

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quadriceps weakness for the duration of a week. All patients had improved back and leg pain at final follow-up, with solid bony fusion seen in 7 patients at 6 months. There were no cases of cage subsidence or mechanical failure.

Drawbacks A study of 227 MIS lumbar discectomies revealed that revision cases resulted in increased re-herniations (15% vs 7%, but not statistically significant), reoperations (32% vs 14%), and postoperative narcotic utilization (112 vs 54 oral morphine equivalents) as compared to primary MIS cases.5 Although, the study5 is not generalizable to other MIS procedures, the same complications should be considered. Another major drawback is that MIS techniques are actively being developed and improved, and the novelty of the procedures may be a barrier in using an MIS approach, especially in a more complex revision case.

Surgical Techniques Lumbar Discectomy MIS revision discectomy is performed by first placing patients prone on a Jackson table with Wilson frame. A tubular retractor (18 mm) is then placed using fluoroscopy or intraoperative computed tomography–guided navigation. Visualization is achieved using an operating microscope. Then, using a side-cutting bur, the previous laminotomy is extended proximally and laterally using a side-cutting burr—any remaining ligamentum flavum is then excised. In cases that require disc fragment removal, a safe plane is identified, and the neural elements are retracted medially to

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gain access and the offending fragments are removed using a pituitary rongeur. Next, any additional ipsilateral lateral recess decompression is performed using Kerrison rongeurs and a side-cutting burr. Finally, contralateral decompression is performed by rotating the surgical bed away from the operating surgeon and undercutting the contralateral lamina to expose the contralateral nerve root and foramen. The contralateral ligamentum flavum is also resected and adequate decompression of the bilateral nerve roots is confirmed through visual inspection.

Fusion After Primary Decompression (TLIF/LLIF) Primary MIS fusion after previous decompression is accomplished using either of two techniques: minimally invasive transforaminal interbody fusion (MI-TLIF) or lateral lumbar interbody fusion (LLIF). MI-TLIF is performed with patients positioned prone on a Jackson table with Wilson frame. Guide wires are placed in bilateral pedicles using either fluoroscopy or intraoperative navigation. A tubular retractor is then placed over the facet joint on the side of primary pathology and complete facetectomy is performed. The disc space is then prepared using a combination of disc prep instruments,18 and an appropriately sized interbody cage packed with iliac crest autograft is placed. Additional iliac crest autograft and local autograft are packed behind the interbody cage. Pedicle screws are then placed over the previously placed guide wires, and rods and set screws are inserted.

Lateral lumbar interbody fusion (LLIF) is performed in a standard fashion.19 Patients

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are positioned in a lateral decubitus position and incision is localized over the target disc space using fluoroscopy or intraoperative image-guided navigation. Abdominal wall musculature is dissected and the retroperitoneum is entered. Dynamic electromyography monitoring is utilized to traverse the psoas muscle and avoid the lumbar plexus in addition to motor and somatosensory evoked potential monitoring throughout the case. A lateral access retractor system is then utilized to perform a complete discectomy and an interbody cage packed with Infuse (Medtronic PLC, Dublin, Ireland) recombinant human bone morphogenic protein-2 is placed to restore disc height and achieve indirect decompression. All patients are then turned to a prone position for percutaneous pedicle screw placement as previously described by our group.20

Revision Fusion After Primary Fusion (TLIF/LLIF) Revision fusion after previous fusion is performed using either MI-TLIF or LLIF surgical techniques described above. After interbody cage placement is completed, previously placed screw fixation is removed using MIS techniques. A 16-mm tubular retractor is docked over each screw, and endcaps are removed one at a time. Once all endcaps are removed, the previously placed rod is removed through either the most proximal or distal percutaneous opening. The tubular retractor is then again docked over each previously placed screw (in order to remove them) and a new larger diameter percutaneous screw is immediately placed into the

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old screw tract (if acceptable). Screws at adjacent levels are placed using fluoroscopy or intraoperative navigation as described above. Finally, a new rod is inserted and locked into place in order to interconnect all screws.

Case Examples Case 1: Failure of Primary Decompression A patient who had undergone primary decompression and laminectomy for lumbar spinal stenosis presented to the hospital with a recurrence of persistent pain and radiculopathy. Imaging revealed postoperative changes including degenerative disc disease and posterior bulges at L4-L5 and L5-S1, respectively (Figure 1). The patient ultimately underwent revision L4-S1 MIS posterior decompression and fusion with TLIF (Figure 2).

Figure 1. Preoperative sagittal CT image revealing L4-S1 degenerative disc disease and posterior bulges.

Figure 2. Sagittal CT image 1 year after L4-S1 PLF and TLIF.

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Case 2: Pseudoarthrosis and Hardware Failure A patient presented to the hospital with persistent low back pain following a primary

Figure 3. Preoperative sagittal CT image revealing L3-L5 pseudoarthrosis/loosening of pedicle screws.

Figure 5. Preoperative sagittal CT image revealing L2-L3 ASD and L5S1 pseudoarthrosis.

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Figure 4. Lateral radiographic image 3 months after L3-L5 LLIF and PLF.

Figure 6. Sagittal CT image 1 year after L3S1 PLF and L2-L3 LLIF.

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L3-L5 lumbar fusion. The indication for the primary procedure was lumbar disc herniation. Imaging prior to the revision indicated L3-L5 pseudoarthrosis with loosening of pedicle screws (Figure 3). The patient underwent revision L3-L5 MIS posterior decompression and fusion with LLIF (Figure 4).

Case 3: Pseudoarthrosis and ASD A patient presented with complaints of low back pain after undergoing a primary L3-S1 LLIF. The primary procedure was indicated due to the presence of L3-L5 anterolisthesis and L5-S1 diffuse disc bulging. Imaging prior to surgery determined that the patient had pseudoarthrosis at the level of L5-S1 and ASD from L2-L3 (Figure 5). The patient underwent revision MIS posterior decompression and fusion from L3-S1 and a L2-L3 LLIF (Figure 6).

Summary Given the significant increase in rates of spinal surgery in the United States over the past decade, the rate of revision surgery is also expected to increase.21 The reoperation rate within the first 5 years after lumbar surgery can be expected to be around 20%, with infection, inadequate decompression, and epidural fibrosis serving as common causes. 22,23 Longer term processes—namely, adjacent segment disease—has been implicated in up to 51% of lumbar spine reoperations.24,25 The approach for each revision surgery should be both personalized to the patient and within the scope of the surgeon’s technical knowledge. According to the literature, it appears that MIS revision techniques pose a viable alternative to their

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“open” counterparts. Additionally, there may be a subset of patients where MIS techniques for revision may offer superior postoperative outcomes. We believe that the concept of

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MIS revision is ripe for further exploration and could eventually represent the preferred treatment modality for revisional spine cases in the future. n

References 1. McAfee PC, Phillips FM, Andersson G, et al. Minimally invasive spine surgery. Spine (Phila Pa 1976).

2010;35(26 suppl):S271-S273.

disc herniations with microdiscectomy and long-term results on life quality: detailed analysis of 70 cases. J Neurosci Rural Pract. 2016;7(1):87-90.

2. Vaishnav AS, Othman YA, Virk SS, Gang CH, Qureshi SA. Current state of minimally invasive spine surgery. J Spine Surg. 2019;5(suppl 1):S2-S10.

10. Dower A, Chatterji R, Swart A, Winder MJ. Surgical management of recurrent lumbar disc herniation and the role of fusion. J Clin Neurosci. 2016;23:44-50.

3. Kalakoti P, Missios S, Maiti T, et al. Inpatient outcomes and postoperative complications after primary versus revision lumbar spinal fusion surgeries for degenerative lumbar disc disease: a national (nationwide) inpatient sample analysis, 20022011. World Neurosurg. 2016;85:114-124.

11. Mendenhall SK, Parker SL, Adogwa O, et al. Long-term outcomes after revision neural decompression and fusion for same-level recurrent lumbar stenosis: defining the effectiveness of surgery. J Spinal Disord Tech. 2014;27(7):353-357.

4. Santos ER, Pinto MR, Lonstein JE, et al. Revision lumbar arthrodesis for the treatment of lumbar cage pseudoarthrosis: complications. J Spinal Disord Tech. 2008;21(6):418-421.

5. Ahn J, Tabaraee E, Bohl DD, Aboushaala K, Singh K. Primary versus revision single-level minimally invasive lumbar discectomy: analysis of clinical outcomes and narcotic utilization. Spine (Phila Pa 1976). 2015;40(18):E1025-E1030.

6. Felbaum DR, Stewart JJ, Distaso C, Sandhu FA. Complication rate in minimally invasive revision lumbar discectomy: a case series and technical note. Clin Spine Surg. 2018;31(5):E266-E269.

7. Hirsch BP, Khechen B, Patel DV, Cardinal KL, Guntin JA, Singh K. Safety and efficacy of revision minimally invasive lumbar decompression in the ambulatory setting. Spine (Phila Pa 1976). 2019;44(8):E494-E499.

12. Selznick LA, Shamji MF, Isaacs RE. Minimally invasive interbody fusion for revision lumbar surgery: technical feasibility and safety. J Spinal Disord Tech. 2009;22(3):207-213.

13. Khan IS, Sonig A, Thakur JD, Bollam P, Nanda A. Perioperative complications in patients undergoing open transforaminal lumbar interbody fusion as a revision surgery. J Neurosurg Spine. 2013;18(3):260-264.

14. Li Z, Tang J, Hou S, et al. Four-year follow-up results of transforaminal lumbar interbody fusion as revision surgery for recurrent lumbar disc herniation after conventional discectomy.

J Clin Neurosci. 2015;22(2):331-7.

15. Wang J, Zhou Y, Zhang ZF, Li CQ, Zheng WJ, Liu J. Minimally invasive or open transforaminal lumbar interbody fusion as revision surgery for patients previously treated by open discectomy and decompression of the lumbar spine.

Eur Spine J. 2011;20(4):623-628.

8. Kogias E, Klingler JH, Franco Jimenez P, et al. Incidental durotomy in open versus tubular revision microdiscectomy: a retrospective controlled study on incidence, management, and outcome.

Clin Spine Surg. 2017;30(10):E1333-E1337.

16. Ba Z, Pan F, Liu Z, et al. Percutaneous endoscopical transforaminal approach versus PLF to treat the single-level adjacent segment disease after PLF/PLIF: 1-2 years follow-up. Int J Surg. 2017;42:22-26.

9. Albayrak S, Ozturk S, Durdag E, Ayden Ö. Surgical management of recurrent

17. Choi YH, Kwon SW, Moon JH, et al. Lateral lumbar interbody fusion and in situ screw

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fixation for rostral adjacent segment stenosis of the lumbar spine. J Korean Neurosurg Soc. 2017;60(6):755-762.

18. Qureshi S. Pearls: improving upon minimally invasive transforaminal lumbar interbody fusion. Clin Orthop Relat Res. 2019;477(3):501-505.

19. Pimenta L. Less-invasive lateral lumbar interbody fusion (XLIF) surgical technique: video lecture. Eur Spine J. 2015;24(suppl 3):441-442.

20. Baird EO, McAnany SJ, Overley S, Skovrlj B, Guzman JZ, Qureshi SA. Accuracy of percutaneous pedicle screw placement: does training level matter? Clin Spine Surg. 2017;30(6):E748-E753.

21. Rajaee SS, Bae HW, Kanim LE, Delamarter RB. Spinal fusion in the United States: analysis of trends from 1998 to 2008.

Spine (Phila Pa 1976). 2012;37(1):67-76.

22. Sato S, Yagi M, Machida M, et al. Reoperation rate and risk factors of elective spinal surgery for degenerative spondylolisthesis: minimum 5-year follow-up.

Spine J. 2015;15(7):1536-1544.

23. Martin BI, Mirza SK, Comstock BA, Gray DT, Kreuter W, Deyo RA. Are lumbar spine reoperation rates falling with greater use of fusion surgery and new surgical technology? Spine (Phila Pa 1976). 2007;32(19):2119-2126.

24. Gerling MC, Leven D, Passias PG, et al. Risk factors for reoperation in patients treated surgically for lumbar Stenosis: a subanalysis of the 8-year data from the SPORT trial. Spine (Phila Pa 1976). 2016;41(10):901-909.

25. Radcliff K, Curry P, Hilibrand A, et al. Risk for adjacent segment and same segment reoperation after surgery for lumbar stenosis: a subgroup analysis of the Spine Patient Outcomes Research Trial (SPORT).

Spine (Phila Pa 1976). 2013;38(7):531-539.

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Hanna Pawlowski, BS

Kevin C. Jacob, BS

Madhav R. Patel, BS

Michael C. Prabhu, BS

Nisheka N. Vanjani, BS

Kern Singh, MD Fall 2021

From Rush University Medical Center in Chicago, Illinois

Development of Alternative Anesthetic Techniques in Spine Surgery Over the years, spine surgeons have traditionally utilized intraoperative general anesthesia and postoperative narcotic medication for most procedures.1 Recently, however, several techniques have been developed to facilitate novel anesthetic approaches to spine surgical patients, aiming to improve both the intraoperative and postoperative aspects of surgery and recovery. Furthermore, with ambulatory surgery centers (ASCs) on the rise and the emphasis on value-based surgical care, additional avenues for cost reduction through alternative a nest het ic approaches have been explored. Notable among these novel techniques are awake spine surgery and multimodal analgesia (MMA) protocols, both of which aim to enhance the patient experience while simultaneously reducing surgical costs.

While general anesthesia has proven safe and effective in the majority of patients, regional anesthesia is becoming increasingly popular among surgeons because of its demonstrated superior outcomes, such as decreases in costs, length of operation, postoperative stay, pain, and in-hospital complications as

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well as increases in patient satisfaction.2 Additionally, as general anesthesia requires intubation for proper breathing, it poses a nontrivial risk to patients with comorbidity burden, especially those patients who have hypertension, who have chronic obstructive pulmonary disease, or who are long-term smokers.

Regional anesthesia mitigates this risk to some extent via conscious facilitation of oxygen delivery by nasal cannulas.

Furthermore, due to reduced occurrence and duration of postoperative nausea, regional anesthesia is deemed favorable, especially for those who are sensitive to nausea.3 Regional anesthesia also reduces the risk of urinary retention, heart, and lung complications that have been observed after use of general anesthesia.4,5 While literature remains scarce, the few studies that have reported on awake spine fusion tout promising results. De Basie et al noted no intraoperative or postoperative complications, as well as no cases converted to general anesthesia in their 10-patient minimally invasive transforaminal lumbar interbody fusion case series.6 In a retrospective rev iew of 100 patients undergoing

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awa ke endoscopic MIS t ransforamina l lumbar interbody fusions, Kolcun et al observed significant improvement in disability and functional status of patients through a minimum 1-year follow-up.7 Upon initial implementation of the same procedure using regional anesthesia, Wang et al noted that spinal outcomes following surgery exceeded the established thresholds for a clinically significant improvement. They also connect the positive outcomes of their patients with beneficial avoidance of postoperative narcotic consumption. 8 Further comparative studies with greater power, however, must be carried out as the majority of literature comes by way of case reports.

Despite the clear advantages of regional anesthesia over general anesthesia and the subsequent benefits of awake spine surgery, limitations exist for patients who are not suitable candidates for regional anesthesia.

Patients with a surgical site infection or who

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outright refuse regional anesthesia are not eligible for regional anesthesia. Additionally, patients younger than 15 years and individuals who may be agitated and restless during the procedure, usually due to anxiety, are also excluded from undergoing regional anesthesia. 9,10 This in turn reduces patient satisfaction and procedural outcomes. Moreover, procedures that exceed the maximum 2.5 hours of regional anesthesia efficacy, such as those involving more than two vertebrae, are more suitable for general anesthesia.2,11,12 With MMA tailored to individual patients and more accessible to procedures using multiple-level fusions, more complex procedures can be performed. Additionally, with MMA protocols more established and researched, the perception of surgical safety increases from the anesthesiologists’ point of view.

Although awake spine surgery has reported success, it is not as well established as an MMA protocol, which was first designed in

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1993 by Kehlet and Dahl.13 Along similar avenues of awake spine surgery, MMA aims to reduce opioid use and provide pain control while simultaneously reducing opioid-related adverse events,14 improving functional outcomes,15 and reducing length of hospital stay.16 In contrast to traditional analgesic techniques, the MMA protocol works in a synergistic manner through simultaneous use of multiple analgesic medications.

At our institution, MMA was developed through a collaboration between surgeons and anesthesiologists, involving a combination of opioids, muscle relaxants, anticonvulsants, and anti-inflammatories simultaneously for synergistic targeting of multiple pain pathways.17 Using an MMA protocol has demonstrated promising results, with multiple studies reporting reduced patient pain, total cost, and length of stay while improving patient recovery time.18-21 Furthermore, from close collaboration with anesthesia colleagues, our research group has deployed an MMA protocol that has allowed us to successfully transition many of our inpatient procedures to an ambulatory setting. In a 50-patient TLIF and LLIF case series, our group reported mean length of stay of 4.5 hours and 3.8 hours for TLIF and LLIF cohorts with no postoperative complications seen in either group. 22 Additionally, our team noted similar positive results when using this protocol for lumbar decompression, with all 499 patients in our case series being discharged on the same day with a postoperative complication rate of only 1.46%.23 Recently, hospitals have shifted toward va lue-based reimbursement models in

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response to rising healthcare costs and subsequent financial pressure. As such, reductions in patient length of stay and hospital costs are desired, but they must not threaten the quality of care delivered to patients. 24 One such way ort hopedic surgeons do so is by performing surgeries in ASCs in which patient discharge is planned for the day of the operation. In a 2016 investigation of 542 patients undergoing lumbar discectomy and laminectomy procedures, Agar wal et al 25 obser ved a 41.1% lower direct operating cost, 36.6% lower indirect cost, and a 39.6% lower total cost for patients placed under regional anesthesia versus those placed under general anesthesia. Furthermore, in a 2014 series of 710 consecutive cer vical and lumbar discectomies, decompression, and fusion spine procedures, Pettine et al reported a 60% cost reduction with the operations that were performed at ASCs compared with those performed at hospitals. 26 A 2019 systematic review by DelSole et al reported that overall, ASC procedures are only 50% to 60% that of hospital outpatient departments. 27 As multimodal anesthetic protocols have proven efficacious over a broader range of spinal techniques in studies with larger power, anesthesiologists will be more comfortable in adapting these protocols in an ambulatory setting vs awake spinal surgery, at least in the near term.

Positive clinical outcomes of patients undergoing MMA protocols, combined with the benefits of ASCs, provide support for use of MMA as a developing alternative to traditional procedures that utilize general

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anesthesia. Surgeons who consider MMA protocols should carefully select patients for eligibility based on a variety of demographic and economic factors that may inf luence their response to regional anesthesia. Moreover, surgeons who are considering adopting

15

MMA protocols into their practice need to consider efficiency and familiarity with the procedure, as previous surgeons conducting this procedure have noted a learning curve present on the part of the surgeon as well as the operative team. n

References 1. Attari MA, Mirhosseini SA, Honarmand A, Safavi MR. Spinal anesthesia versus general anesthesia for elective lumbar spine surgery: a randomized clinical trial.

J Res Med Sci. 2011;16(4):524-529.

2. Fiani B, Reardon T, Selvage J, et al. Awake spine surgery: an eye-opening movement.

Surg Neurol Int. 2021;12(222):222.

3. Bajwa SJS, Kulshrestha A. Anaesthesia for laparoscopic surgery: general vs regional anaesthesia. J Minim Access Surg. 2016;12(1):4-9.

4. McLain RF, Kalfas I, Bell GR, Tetzlaff JE, Yoon HJ, Rana M. Comparison of spinal and general anesthesia in lumbar laminectomy surgery: a case-controlled analysis of 400 patients. J Neurosurg Spine. 2005;2(1):17-22.

5. Tufts Medical Center. Spinal anesthesia vs. general anesthesia. Accessed October 15, 2021. https://www.tuftsmedicalcenter.org/news-events-media/news/web/spinal-anesthesia 6. De Biase G, Bechtle P, Leone B, Quinones-Hinojosa A, Abode-Iyamah K. Awake minimally invasive transforaminal lumbar interbody fusion with a pedicle-based retraction system. Clin Neurol Neurosurg. 2021;200:106313.

7. Kolcun JPG, Brusko GD, Basil GW, Epstein R, Wang MY. Endoscopic transforaminal lumbar interbody fusion without general anesthesia: operative and clinical outcomes in 100 consecutive patients with a minimum 1-year follow-up.

Neurosurg Focus. 2019;46(4):E14.

8. Wang MY, Grossman J. Endoscopic minimally invasive transforaminal interbody fusion without general anesthesia: initial clinical experience with 1-year follow-up.

Neurosurg Focus. 2016;40(2):E13.

9. Ames WA, Songhurst L, Gullan RW. Local anaesthesia for laminectomy surgery.

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Br J Neurosurg. 1999;13(6):598-600.

10. Collins LM, Vaghadia H. Regional anesthesia for laparoscopy. Anesthesiol Clin North Am. 2001;19(1):43-55.

11. Wang MY, Lu Y, Greg Anderson D, Mummaneni PV. Minimally Invasive Spinal Deformity Surgery: An Evolution of Modern Techniques. Springer Science & Business Media; 2014.

12. Khan MB, Kumar R, Enam SA. Thoracic and lumbar spinal surgery under local anesthesia for patients with multiple comorbidities: a consecutive case series.

Surg Neurol Int. 2014;5(Suppl 3):S62-S65.

13. Kehlet H, Dahl JB. The value of “multimodal” or “balanced analgesia” in postoperative pain treatment.

Anesth Analg. 1993;77(5):1048.

14. Dirkmann D, Groeben H, Farhan H, Stahl DL, Eikermann M. Effects of parecoxib on analgesia benefit and blood loss following open prostatectomy: a multicentre randomized trial. BMC Anesthesiol. 2015;15:31.

15. Elvir-Lazo OL, White PF. The role of multimodal analgesia in pain management after ambulatory surgery. Curr Opin Anaesthesiol. 2010;23(6):697-703.

16. Michelson JD, Addante RA, Charlson MD. Multimodal analgesia therapy reduces length of hospitalization in patients undergoing fusions of the ankle and hindfoot.

Foot Ankle Int. 2013;34(11):1526-1534.

17. Yoo JS, Ahn J, Buvanendran A, Singh K. Multimodal analgesia in pain management after spine surgery. J Spine Surg. 2019;5(Suppl 2):S154-S159.

18. Wang MY, Chang HK, Grossman J. Reduced acute care costs with the ERAS® minimally invasive transforaminal lumbar interbody fusion compared with conventional minimally invasive

transforaminal lumbar interbody fusion.

Neurosurgery. 2017;83(4):827-834.

19. Kahokehr A, Sammour T, Zargar-Shoshtari K, Thompson L, Hill AG. Implementation of ERAS and how to overcome the barriers. Int J Surg. 2009;7(1):16-19.

20. Kehlet H. Multimodal approach to control postoperative pathophysiology and rehabilitation. Br J Anaesth. 1997;78(5):606-617.

21. Kehlet H, Wilmore DW. Multimodal strategies to improve surgical outcome.

Am J Surg. 2002;183(6):630-641.

22. P arrish JM, Jenkins NW, Brundage TS, et al. Outpatient minimally invasive lumbar fusion using multimodal analgesic management in the ambulatory surgery setting. Int J Spine Surg. 2020;14(6):970-981.

23. N olte MT, Parrish JM, Jenkins NW, et al. Multimodal analgesic management for lumbar decompression surgery in the ambulatory setting: clinical case series and review of the literature. World Neurosurg. 2021;154:e656-e664.

24. B asil GW, Wang MY. Trends in outpatient minimally invasive spine surgery. J Spine Surg. 2019;5(suppl 1):S108-S114.

25. A garwal P, Pierce J, Welch WC. Cost analysis of spinal versus general anesthesia for lumbar diskectomy and laminectomy spine surgery. World Neurosurg. 2016;89:266-271.

26. P ettine K, Mohnssen CR. Spine surgery at an ambulatory surgery center. Presented at ISASS14 Annual Conference; Thursday, May 1, 2014; Miami Beach, Florida.

27. DelSole EM, Makanji HS, Kurd MF. Current trends in ambulatory spine surgery: a systematic review. J Spine Surg. 2019;5(suppl 2):S124-S132.

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From The Core Institute in Mesa, Arizona

Interfacet Spacers for Minimally Invasive Posterior Cervical Fusion An Update on the Literature Posterior cervical fusion is employed for a variety of indications within spine surgery, including the prevention of postlaminectomy kyphosis, deformity correction, as well as both prevention Brandon P. Hirsch, MD and subsequent treatment of pseudarthrosis following anterior cervical discectomy and fusion (ACDF). Traditional posterior cervical fusion technique employs segmental fixation through screw and rod constructs. This technique tends to be rather invasive given the need to dissect the paraspinal musculature in order to place this instrumentation. While minimally invasive approaches to screw and rod fixation have been described, they tend to be technically difficult with regard to rod passage and maintaining visualization through a muscle sparing approach.1 Transfacet screw fixation without use of a connecting rod has also been described but has not gained widespread adoption due to the challenges associated with imaging the complex 3-dimensional anatomy of the cervical posterior elements and concerns over limited ability to create a robust fusion surface.2 Interfacet spacers with conduits for fusion have emerged as a minimally invasive option for indirect decompression, stabilization, and arthrodesis of the posterior cervical spine.

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This technique placed via open exposure and utilizing circular spacers filler with iliac crest autograft was initially described by Goel for the treatment of both radiculopathy and myelopathy.3 Since Goel’s description, implant design and technique have been further refined to allow for joint space decortication and placement of interfacet cages through a muscle sparing tubular approach. Early cadaveric studies of these devices have demonstrated their ability to achieve stability and increase foraminal height/area.4,5 Subsequent investigations have gone on to evaluate their clinical utility in treating radiculopathy and pseudarthrosis and in providing supplemental fixation for multilevel anterior cervical fusion.

Use for Radiculopathy McCormack et al6 studied the use of a titanium expandable facet shim as a means of treating patients with radiculopathy at a single cervical level. These patients received bilateral interfacet devices placed through a fluoroscopically guided paramedian approach. Facets were grafted with cancellous allograft mixed with iliac crest aspirate. Sixty patients were included with 1-year clinical and radiographic follow-up performed by an independent research organization. The authors found that the Neck Disability Index (NDI), 12-item Short Form Health Survey, and visual analog scale (VAS)

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INSTRUMENTATION

scores were all significantly improved at 12 months, and the authors reported a fusion rate of 93% at 1 year. There were no reoperations, but the authors did report 4 facet fractures, which led to redesign of instruments used to access the facet. Foraminal height and volume were significantly increased at 6 months but returned to baseline measurements by 1 year.

Siemionow et al7 reported 2-year outcomes of this series, which were essentially equivalent to the 1-year clinical results. Foraminal dimensions were not reported. The fusion rate was reported at 98%. No additional data on reoperation were reported.

Ramos et al8 recently evaluated multilevel percutaneous posterior cervical fusion utilizing interfacet spacers. Their study population included 30 patients receiving 2-, 3-, or 4-level fusion procedures with facet spacers via a tissue sparing incision. The authors reported excellent reduction in NDI (7 vs 65, P < 0.001), VAS arm (0.4 vs 8.4, P < 0.001), and VAS scores (0.8 vs 4.4, P < 0.001), at 2-year follow-up. Fusion rates at 2 years were 75% for 4-level cases, 85.7% for 3-level cases, and 100% for 2-level cases. One patient had a medially positioned implant that required revision but caused no neurologic injury.

average follow-up of 20 months. They reported 100% fusion of levels treated for pseudarthrosis. Smith et al10 retrospectively analyzed 25 patients treated with a muscle sparing technique across 1 to 4 levels. Of these patients, 9 had a combined anterior approach to treat kyphosis or ventral spinal cord compression.

The authors reported favorable outcome scores for the group as a whole but did not separate out outcomes for the 16 patients treated with isolated interfacet spacer placement. However, both studies separately reported a 94% fusion rate in this cohort.

Use for Pseudarthrosis Although some advocate for use of interfacet cages as a less invasive treatment for pseudarthroses after anterior cervical fusion, few studies has been published assessing this indication. Kasliwal et al9 described outcomes in 19 patients treated for pseudarthrosis with open placement of allograft facet spacers. They reported statistically significant improvements in VAS neck, VAS arm, and NDI scores at an

Effect of Interfacet Spacers on Alignment Generation of kyphosis is one of the primary concerns associated with the use of interfacet devices due to the distraction applied to the posterior elements during insertion. The early study of single-level application published

by McCormack et al6 did note a significant decrease in segmental lordosis at the treated level of 1.6° (P < 0.05) on average. Overall cer-

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Use for Supplemental Fixation Posteriorly Only 1 study has evaluated the use of interfacet spacers for supplemental fixation in multilevel ACDF. Kramer et al11 retrospectively evaluated 35 patients who underwent multilevel ACDF and had either 3 or more level surgery or 2 or more level surgery with risk factors for pseudarthrosis. Iliac crest autograft was used. Only combined VAS was reported with a reduction from 7.6 preoperatively to 2.8 postoperatively (P < 0.0001). There were 2 superficial wound infections but no other adverse events.

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vical lordosis was not significantly different at this time point. Tan et al12 studied the effect of interfacet spacers on cervical lordosis in 45 patients treated at 154 levels. These authors performed an open technique and did not find any appreciable difference in overall cervical lordosis. Individual level changes in alignment were not reported. In the most recent study involving 30 patients treated with a multilevel percutaneous technique, Ramos et al8 reported a loss of 7.1° of overall lordosis at 2-year follow-up with an increase of 6.9 mm in cervical sagittal vertical axis. This is currently the only study evaluating alignment in multilevel use of interfacet spacers without an anterior construct.

Conclusion Overall, studies on the use of percutaneous cervical interfacet spacers for posterior fusion

suggest that there is significant clinical benefit to the technique in the form of high fusion rates and excellent reduction in neck and arm pain.

The published literature also suggests that the procedure is associated with a low complication rate, less postoperative pain, and a shorter length of stay.13 The current available data on single level application are mixed with regard to generation of kyphosis. The application of this technique in multilevel constructs does seem to reduce overall cervical lordosis as indicated by Ramos et al.8 This finding is most likely related to the inability of other unfused levels to compensate in multilevel constructs. In contrast, patients undergoing a 1-level procedure have additional open disc levels that can compensate for the generation of kyphosis. Although clinical outcomes appear positive, more data are needed to understand the impact of this technique on global cervical alignment. n

References 1. Mikhael MM, Celestre PC, Wolf CF, Mroz TE, Wang JC. Minimally invasive cervical spine foraminotomy and lateral mass screw placement. Spine. 2012;37(5):E318-E322.

2. Ahmad F, Sherman JD, Wang MY. Percutaneous trans-facet screws for supplemental posterior cervical fixation.

World Neurosurg. 2012;78(6):716.e1-4.

3. Goel A, Shah A. Facetal distraction as treatment for single- and multilevel cervical spondylotic radiculopathy and myelopathy: a preliminary report. J Neurosurg Spine. 2011;14(6):689–696.

4. Leasure JM, Buckley J. Biomechanical evaluation of an interfacet joint decompression and stabilization system. J Biomechan Eng. 2014;136(7):0710101-0710108.

5. Tan LA, Gerard CS, Anderson PA, Traynelis VC. Effect of machined interfacet allograft spacers on cervical foraminal height and area. J Neuro-

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surg Spine. 2014;20(2):178-182.

6. McCormack BM, Bundoc RC, Ver MR, Ignacio JM, Berven SH, Eyster EF. Percutaneous posterior cervical fusion with the DTRAX Facet System for single-level radiculopathy: results in 60 patients. J Neurosurg Spine. 2013;18(3):245-254.

7. Siemionow K, Janusz P, Phillips FM, et al. Clinical and radiographic results of indirect decompression and posterior cervical fusion for single-level cervical radiculopathy using an expandable implant with 2-year follow-up. J Neurol Surg A Cent Eur Neurosurg. 2016;77(6):482-488.

8. Ramos MRD, Mendoza CJP, Yumol JV, Joson RS, Ver MLP, Ver MR. Multilevel, percutaneous posterior cervical interfacet distraction and fusion for cervical spondylotic radiculopathy.

Spine. 2021;46(21):E1146-E1154.

9. Kasliwal MK, Corley JA, Traynelis VC. Posterior cervical fusion using cervi-

cal interfacet spacers in patients with symptomatic cervical pseudarthrosis.

Neurosurgery. 2016;78(5):661-668.

10. Smith W, Gillespy M, Huffman J, Vong V, McCormack BM. Anterior cervical pseudarthrosis treated with bilateral posterior cervical cages. Oper Neurosurg (Hagerstown). 2018;14(3):236-242.

11. Kramer S, Albana MF, Ferraro JB, et al. Minimally invasive posterior cervical fusion with facet cages to augment high-risk anterior cervical arthrodesis: a case series.

Global Spine J. 2020;10(2 suppl):56S-60S. 12. Tan LA, Straus DC, Traynelis VC. Cervical interfacet spacers and maintenance of cervical lordosis. J Neurosurg Spine. 2015;22(5):466-469.

13. Cofano F, Sciarrone GJ, Federico Pecoraro M, et al. Cervical interfacet spacers to promote indirect decompression and enhance fusion in degenerative spine: a review.

World Neurosurg. 2019;126:447-452.

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From the Hospital for Special Surgery in New York, New York

DEFORMITIES

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Minimally Invasive Surgical Approaches to Spinal Deformity Patients with adult spinal deformity (ASD) experience severe pain and morbidity that can lead to a significant reduction in quality of life. Given this significant impact on quality of life and function, patients often seek operative management when conservative measures fail. However, surgical treatment of ASD has historically ut ilized highly invasive open surgical techniques, which can result in significant intraoperative and postoperative complications and morbidity.

The introduction of minimally invasive surgical (MIS) techniques in recent years may provide an attractive alternative that can provide the benefits of surgical management of ASD while minimizing the complications and long-term sequelae of more traditional open techniques.1 By decreasing muscle crush, maintaining tendon attachments to the posterior elements, and maintaining the dorsolumbar fascia, MIS helps to limit tissue damage to the specific planes and corridors necessary for insertion of instrumentation.

When Are MIS Approaches Appropriate?

Impact of Approach and Technique In the management of ASD, re-establishment of sagittal and coronal balance is extremely important given their influence on patient disabilit y and outcomes. 2,3 In general, a sagittal vertical axis of less than 5 cm and

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pelvic incidence-lumbar lordosis (PI-LL) mismatch less than 10° are considered optimal. 4,5 Prev ious st ud ies compa r i ng circumferential MIS, hybrid, and open techniques for correction of ASD have found t hat MIS Greg Kazarian, MD techniques may have difficulty correcting larger deformities.4,6-8 Based on such findings, the use of traditional MIS techniques is often restricted to patients with a sagittal vertical axis less than 6 cm and PI-LL mismatch less than Yeo Eun Kim, MD 10°. However, new techniques are being developed that will allow for correction of larger deformities. The introduction of circumferential MIS techniques,9,10 for example, has allowed for the utilization of hyperlordotic cages that may allow for lordosis Sravisht Iyer, MD correction as high as 13° to 15°,11 with correction similar to pedicle subtraction osteotomy (PSO) at 1 year.9 Multiple studies have show n that the approach is perhaps the most important factor in attaining maximum segmental lordosis (SL) in MIS for ASD. A retrospective study comparing SL outcomes from various circumferential MIS techniques for ASD demonstrated that greater SL was attained

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using anterior column release (ACR) at L2-3 and L3-4 levels and using anterior lumbar interbody fusion (ALIF) at the L4-5 and L5S1 levels.12 On average, a SL of 10.9° at L2-L3 and 10.4° at L3-L4 could be created with ACR. On average, a SL of 9.2° at L4-L5 and 5.3° at L5-S1 could be created with ALIF. Similarly, another study found that ALIF generates the greatest segmental lordosis compared to other approaches, including lateral lumbar interbody fusion (LLIF) and transforaminal lumbar interbody fusion (TLIF), irrespective of cage lordotic angle.

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The change in SL achieved postoperatively was greatest with ALIF, at 9.8°, compared to 1.8° for both TLIF and LLIF. Furthermore, it was demonstrated that anterior positioning of the cage was the only factor that independently correlated with greater SL gain, with anteriorly placed cages gaining 4.2° of lordosis vs 0.3° of kyphosis for posteriorly placed cages.13 When the impact of various lumbar fusion techniques was compared in 164 patients treated with ALIF, TLIF, posterior lumbar interbody fusion (PLIF), or LLIF at a single

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DEFORMITIES

level, it was found that ALIF was the most effective in improving PI-LL mismatch (which correlates with a better sagittal alignment) and the only technique to provide a significant improvement in the proportion of patients with a PI-LL of less than 10°. Segmental lordosis was also shown to be more heavily inf luenced by the approach over implant geometry,14 suggesting that anterior-based interbody techniques optimize MIS deformity correction.

Recently, an algorithm was developed for considering MIS techniques in correction of ASD. The framework recommends MIS for low to moderate or flexible deformities while advising against MIS approaches in patients with high PI-LL mismatch. For rigid spines, it recommends additional releases, whether it be through ACR or mini-open or open posterior osteotomies.1 A review of the experience at our institution has shown that the correction obtained via MIS (especially in the sagittal plane) is best approximated by the supine scout CT images or supine radiographs. If the “relaxed” supine images demonstrate insufficient correction of lumbar lordosis, surgeons should be prepared for more extensive anterior (ACR) or posterior (mini-open osteotomy) releases to ensure appropriate correction.

Factors Driving Adoption of MIS Single Position The growth of additional single-position techniques (prone lateral, lateral ALIF) has made it technically feasible for surgeons to address all the levels from the thoracolumbar to the lumbosacral junction in a minimally

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invasive fashion without requiring changes in position. In flexible curves, this allows for powerful correction of deformity.

Compared to multiple positions, there seems to be a significant advantage to single-position lumbar surgeries in MIS correction of deformities. A retrospective study

by Buckland et al17 showed single-position lumbar surgeries significantly reduced the operation time, length of stay, and fluoroscopy radiation dosage.

Robotic Assistance While screw placement in the thoracic and lumbar spine using navigation or fluoroscopy was always possible, the introduction of robotics allows surgeons to carefully plan screw trajectories to maximize purchase in the pedicle and enable easy rod passage; this becomes particularly advantageous in long constructs with pelvic fixation. Although robotics has been shown to increase operative time in certain instances, the advantages of robotics become more pronounced and the time “cost” less severe as the number of fusion levels increases.

Why Are MIS Approaches Beneficial?

Various studies have demonstrated the advantages of MIS over open procedures. A retrospective study by Uribe et al reported that MIS approaches significantly reduced levels of fusion, blood loss, and length of stay in ASD surgeries.15 When compared with open surgeries and hybrid procedures, MIS approaches were shown to produce significantly fewer intraoperative complications compared to both methods,16 though the

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differences were small. However, a recent systematic review of recent literature found no conclusive evidence that MIS approaches are superior to other approaches.2

Conclusion It is important, therefore, not to overstate the benefits of MIS for this patient population but recognize that it is a complementary approach for the treatment of moderate, flexible deformities. As with all new tech-

niques, the success of MIS approaches is ultimately driven by appropriate patient selection; aggressive application of MIS techniques to inappropriate curves is likely to lead to undercorrection and may incur an increased risk of complications. However, in appropriately indicated cases, recent advances in technology make minimally invasive approaches a viable and sometimes more attractive option. n

References 1. Mummaneni PV, Park P, Shaffrey CI, et al. The MISDEF2 algorithm: an updated algorithm for patient selection in minimally invasive deformity surgery. J Neurosurg Spine. 2019;32(2):221-228.

2. Zanirato A, Damilano M, Formica M, et al. Complications in adult spine deformity surgery: a systematic review of the recent literature with reporting of aggregated incidences.

Eur Spine J. 2018;27(9):2272-2284.

3. Theologis AA, Mundis Jr GM, Nguyen S, et al. Utility of multilevel lateral interbody fusion of the thoracolumbar coronal curve apex in adult deformity surgery in combination with open posterior instrumentation and L5-S1 interbody fusion: a case-matched evaluation of 32 patients.

J Neurosurg Spine. 2017;26(2):208-219.

4. Park P, Fu K-M, Mummaneni PV, et al.

The impact of age on surgical goals for spinopelvic alignment in minimally invasive surgery for adult spinal deformity. J Neurosurg Spine. 2018;29(5):560-564.

5. Smith JS, Shaffrey CI, Bess S, et al. Recent and emerging advances in spinal deformity. Neurosurgery. 2017;80(3S):S70-S85.

6. Anand N, Baron EM, Khandehroo B. Limitations and ceiling effects with circumferential minimally invasive correction techniques for adult scoliosis: analysis of radiological outcomes over a 7-year experience. Neurosurg Focus. 2014;36(5):E14.

7. Than KD, Park P, Fu K-M, et al. Clinical and radiographic parameters associated

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with best versus worst clinical outcomes in minimally invasive spinal deformity surgery. J Neurosurg Spine. 2016;25(1):21-25.

8. Mundis Jr GM, Turner JD, Deverin V, et al. A critical analysis of sagittal plane deformity correction with minimally invasive adult spinal deformity surgery: a 2-year follow-up study.

Spine Deform. 2017;5(4):265-271.

9. Mundis Jr GM, Turner JD, Kabirian N, et al.

Anterior column realignment has similar results to pedicle subtraction osteotomy in treating adults with sagittal plane deformity. World Neurosurg. 2017;105:249-256.

10. Wang MY, Bordon G. Mini-open pedicle subtraction osteotomy as a treatment for severe adult spinal deformities: case series with initial clinical and radiographic outcomes. J Neurosurg Spine. 2016;24(5):769-776.

11. Demirkiran G, Theologis AA, Pekmezci M, Ames C, Deviren V. Adult spinal deformity correction with multi-level anterior column releases: description of a new surgical technique and literature review.

Clin Spine Surg. 2016;29(4):141-149.

12. Mummaneni PV, Hussain I, Shaffrey CI, et al. The minimally invasive interbody selection algorithm for spinal deformity [published online ahead of print]. J Neurosurg Spine. https://doi. org/10.3171/2020.9.SPINE20230 13. Lovecchio FC, Vaishnav AS, Steinhaus ME, et al. Does interbody cage lordosis impact actual segmental lordosis achieved in

minimally invasive lumbar spine fusion?

Neurosurg Focus. 2020;49(3):E17.

14. Ahlquist S, Park HY, Gatto J, Shamie AN, Park DY. Does approach matter? A comparative radiographic analysis of spinopelvic parameters in single-level lumbar fusion. Spine J. 2018;18(11):1999-2008.

15. Uribe JS, Beckman J, Mummaneni PV, et al. Does MIS surgery allow for shorter constructs in the surgical treatment of adult spinal deformity?

Neurosurgery. 2017;80(3):489-497.

16. Uribe JS, Deukmedjian AR, Mummaneni PV, et al. Complications in adult spinal deformity surgery: an analysis of minimally invasive, hybrid, and open surgical techniques. Neurosurg Focus. 2014;36(5):E15.

17. Buckland AJ, Ashayeri K, Leon C, et al.

Single position circumferential fusion improves operative efficiency, reduces complications and length of stay compared with traditional circumferential fusion. Spine J. 2021;21(5):810-820.

18. D’Souza M, Gendreau J, Feng A, Kim LH, Ho AL, Veeravagu A. Robotic-assisted spine surgery: history, efficacy, cost, and future trends. Robot Surg. 2019;6:9-23.

19. Han X, Tian W, Liu Y, et al. Safety and accuracy of robot-assisted versus fluoroscopy-assisted pedicle screw insertion in thoracolumbar spinal surgery: a prospective randomized controlled trial. J Neurosurg Spine. 2019:1-8.

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BIOLOGICS

From the Zucker School of Medicine at Hofstra/Northwell in New Hyde Park, New York (Dr Perfetti), and the Texas Back Institute in Plano, Texas (Drs Derman and Satin)

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Live Cellular Allografts Spinal fusion is one of the most common procedures for treating spinal conditions, including degenerative disc disease, deformity, spondylolisthesis, and trauma. A critical component to achieving a successful arthrodesis is the bone graft or graft substitute utilized. Autologous bone from either the iliac crest or local bone graft near the surgical site is considered the gold standard graft as it intrinsically contains osteoconductive, osteoinductive, and osteogenic properties. However, harvesting autologous bone is associated with increased operative time, increased donor site morbidity, and limitations in quantity or quality of host bone.1,2 These limitations have led to the creation of multiple bone graft substitutes, bone graft extenders, and osteobiologics.

Advancements in regenerative medicine and stem cell technology have led to the development of live cellular allografts, also known as cellular bone matrices (CBMs). These products are unique in that they possess osteogenic potential, which is not present in acellular allograft products.

CBMs are created using osteoconductive cadaveric bone with retention or addition of live mesenchymal stem cells (MSCs). These multipotent adult stem cells are capable of self-renewal and give rise to all cells of the mesoderm, including bone. 3 Most are isolated from bone marrow, although they can be isolated from other sources such as placenta, umbilical cord blood, connective tissue, skin, and fat.4 MSCs do not ex-

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press human leukocyte antigen Class II molecules essential for activation of cellular immune response, thus resisting immunologic rejection. 5 CBMs are not terminally sterilized and rely on aseptic processing to ensure Dean Perfetti, MD, MPH safety. Stem cell differentiation into osteoblasts is inf luenced by spatial organization, density, mechanical forces, cytokines, and other bioactive nutrients.6 The exact cell density, carrier procurements, and preparations in commercially available CBMs vary due to the proprietary na- Peter B. Derman, ture of the processes used to MD, MBA create these products. Important distinctions between commercially available CBMs are the tissue of origin and the donor age at the time of graft harvest.6 W hile an opt ima l donor age range for harvesting of MSCs is unknown, age plays a critical Alexander Satin, MD role on the number, function, osteoblastic potential, and cytokine production of MSCs.6 Additionally, the percentage of MSCs within the CBMs capable of surviving in the fusion bed after transplantation is a critical factor.

The majority of preclinical animal studies investigating the efficacy of stem cells in promoting fusion demonstrate that MSCs with supporting scaffolds can at the very least approach or match the fusion rates

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achieved with autografts.7 However, clinical studies examining the efficacy of MSCs are limited and further confounded by both the variability among commercial products and their production lots.8 The HCT/P (human cells, tissues, and cellular and tissue-based products) classification does not require lot-to-lot cell composition or validation of growth factor production. 8 Nonetheless, these novel CBM products represent roughly a 10% share of the spine biologics market, estimated at $2.4 billion in 2020. 9,10 In the following paragraphs, we discuss the clinical outcomes regarding a variety of commercially available CBMs.

Trinity Evolution/Elite (Orthofix, Lewisville, TX, USA)11-13 Trinity Evolution is a cryopreserved allograft consisting of viable cellular cancellous bone matrix and demineralized cortical bone. It contains a minimum of 250,000 cells per cc, 50,000 of which are validated to be MSCs and/or osteoprogenitor cells. Cell viability data are not available. Its average donor age is 30 years.14 Trinity Elite builds on Trinity Evolution as a third-generation allograft processed using a moldable, fiber-based scaffold without an additional carrier. Trinity Elite claims greater than 70% cell viability and contains a minimum of 500,000 cells per cc, of which 100,000 are validated to be adult mesenchymal stem cells and/or osteoprogenitor cells.13 Trinity Evolution has been investigated in human clinical studies. Vanichkachorn et al15 performed a retrospective study to evaluate the safety and efficacy of Trinity Evolution in a

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cohort of 21 patients undergoing single-level anterior cervical discectomy and fusion (ACDF) and found an overall fusion rate of 78.6% at 6 months and 93.5% at 12 months.

In their prospective study, Peppers et al16 found 12-month fusion rates for 2-level ACDF with Trinity Evolution to be 93.4%. Musante et al17 retrospectively found 12-month fusion rates for 1- and 2-level posterolateral fusion to be 90.7% and 89.5%, respectively.

Osteocel; Osteocel Plus (NuVasive, San Diego, CA, USA)18; (ACE Surgical Supply Co., Brockton, MA, USA)19 Osteocel Plus is an allograft CBM containing osteoprogenitor cells, MSCs, osteoblasts, and other cells along the osteogenic lineage combined with DBM. It contains more than 250,000 cells per cc with over 70% cell viability.19 Eastlack et al 20 prospectively evaluated 2-year outcomes for single- and multilevel ACDF utilizing Osteocel Plus in 182 patients at 249 levels; they demonstrated a 92% single-level fusion rate at 24 months and an 87% overall fusion rate when including multilevel.

Tohmeh et al 21 evaluated arthrodesis rates in patients who underwent lateral lumbar interbody fusion with Osteocel Plus at 12 months postoperatively, including 40 patients at a total of 61 levels. Successful single-level interbody fusion utilizing the lateral lumbar interbody fusion technique and Osteocel Plus was shown in 90.2% of the levels by 12-month follow-up. 21 Ammerman et al 22 published a retrospective study investigating Osteocel Plus for transforaminal lumbar interbody fusion in 23 patients and 26 levels; they demonstrated a 91.3% fusion rate by 12

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months. The only non–industry-sponsored study was performed by McAnany et al,23 who studied a cohort of 57 patients undergoing ACDF with standard plating and Osteocel Plus compared to a matched control group of 57 patients with standard allograft. The authors found a lower fusion rate in the Osteocel group (87.7%) compared to the control cohort (94.7%), though this difference was not statistically significant (P = 0.19). 23

ViviGen (LifeNet Health, San Diego, CA, USA)24 ViviGen is a CBM incorporating lineage committed bone cells (MSCs removed), corticocancellous chips, and demineralized bone.

Cell count information is not available, but 96% cell viability is reported.24 Elgafy et al 25 performed a retrospective study of multilevel instrumented posterior lumbar fusion with ViviGen (96 patients, 222 levels) and observed a 91.7% fusion rate by 16 months.25 Hall et al, 26 in a retrospective study of ViviGen in the setting of multilevel posterolateral fusion (150 patients, 613 levels), demonstrated a

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25

98.7% fusion rate at 12 months. Gibson et al 27 performed a prospective study assessing multilevel ACDF with or without ViviGen and demonstrated no significant difference in fusion rates between the two at 1 year (92.9% in the Vivigen group; 84% in the group without ViviGen; P = 0.404).

Conclusion CBMs containing MSCs and/or osteoprogenitor cells as an adjunct or alternative to autograft is an emerging field of research.

There are few comparative clinical studies with well-defined spinal fusion cohorts assessing CBMs in relation to other biologic products. None of these products have been approved by the US Food and Drug Administration, as CBMs meet criteria for HCT/P exemption from federal 510(k) submission requirements.28 While CBMs remain a commercially available and promising alternative to autograft, more non–industry-sponsored clinical studies are needed to compare various CBMs in terms of costs, fusion rates, and complication profiles. n

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References 1. Sasso RC, LeHuec JC, Shaffrey C; the Spine Interbody Research Group. Iliac crest bone graft donor site pain after anterior lumbar interbody fusion: a prospective patient satisfaction outcome assessment.

Clin Spine Surg. 2005;18(suppl):S77-S81.

2. Kurz LT, Garfin SR, Booth Jr RE. Harvesting autogenous iliac bone grafts. A review of complications and techniques. Spine (Phila Pa 1976). 1989;14(12):1324-1331.

3. Yelick PC, Zhang W. Mesenchymal stem cells. In: Fisher JP, Mikos AG, Bronzino JD, Peterson DR, eds. Tissue Engineering: Principles and Practices. Taylor & Francis Group; 2012.

4. Sethe S, Scutt A, Stolzing A. Aging of mesenchymal stem cells. Ageing Res Rev. 2006;5(1):91-116.

5. Ryan JM, Barry FP, Murphy JM, Mahon BP. Mesenchymal stem cells avoid allogeneic rejection. J Inflamm (Lond). 2005;2:8.

6. Skovrlj B, Guzman JZ, Al Maaieh M, Cho SK, Iatridis JC, Qureshi SA. Cellular bone matrices: viable stem cell-containing bone graft substitutes.

Spine J. 2014;14(11):2763-2772.

7. Stephan SR, Kanim LE, Bae HW. Stem cells and spinal fusion. Int J Spine Surg. 2021;15(suppl 1):S94-S103.

8. Cohen JD, Kanim LE, Trontis AJ, Bae HW. Allografts and spinal fusion. Int J Spine Surg. 2021;15(suppl 1):S68-S93.

9. Abjornson C, Brecevich A, Callanan T, Dowe C, Cammisa FP, Lorio MP. ISASS recommendations and coverage criteria for bone graft substitutes used in spinal surgery. Int J Spine Surg. 2018;12(6):757-771.

10. Diaz RR, Savardekar AR, Brougham JR, Terrell D, Sin A. Investigating the efficacy of allograft cellular bone matrix for spinal fusion: a systematic review of the literature. Neurosurg Focus. 2021;50(6):E11.

11. Orthofix Medical Inc. Trinity Evolution: An Allograft With Viable Cells [brochure]. https://www.orthofix. com/wp-content/uploads/2019/01/ Trinity-Evolution-Brochure.pdf 12. Orthofix Medical Inc. Trinity Elite: Allograft With Viable Cells [brochure]. https://www.orthofix.com/ wp-content/uploads/2020/12/TT1903-Trinity-ELITE-Trifold-DFNL.pdf

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13. Orthofix. Trinity Elite Technical Monograph: A Fully Moldable Allograft With Viable Cells. https://www.orthofix.com/ brazil/wp-content/uploads/2019/01/ Trinty-ELITE-Technical-Monograph.pdf.

14. Orthofix. Trinity evolution: instructions for use. https://www.orthofix. com/wp-content/uploads/2019/01/ Trinty-Evolution-IFU.pdf 15. Vanichkachorn J, Peppers T, Bullard D, Stanley SK, Linovitz RJ, Ryaby JT. A prospective clinical and radiographic 12-month outcome study of patients undergoing single-level anterior cervical discectomy and fusion for symptomatic cervical degenerative disc disease utilizing a novel viable allogeneic, cancellous, bone matrix (trinity evolution) with a comparison to historical controls.

Eur Spine J. 2016;25(7):2233-2238.

16. Peppers TA, Bullard DE, Vanichkachorn JS, et al. Prospective clinical and radiographic evaluation of an allogeneic bone matrix containing stem cells (Trinity Evolution® Viable Cellular Bone Matrix) in patients undergoing two-level anterior cervical discectomy and fusion.

J Orthop Surg Res. 2017;12(1):67.

17. Musante DB, Firtha ME, Atkinson BL, Hahn R, Ryaby JT, Linovitz RJ. Clinical evaluation of an allogeneic bone matrix containing viable osteogenic cells in patients undergoing one- and two-level posterolateral lumbar arthrodesis with decompressive laminectomy. J Orthop Surg Res. 2016;11:63.

18. NuVasive Inc. Osteocel. https:// www.nuvasive.com/procedures/ featured-offerings/osteocel/

22. Ammerman JM, Libricz J, Ammerman MD. The role of Osteocel Plus as a fusion substrate in minimally invasive instrumented transforaminal lumbar interbody fusion. Clin Neurol Neurosurg. 2013;115(7):991-994.

23. M cAnany SJ, Ahn J, Elboghdady IM, et al. Mesenchymal stem cell allograft as a fusion adjunct in one- and two-level anterior cervical discectomy and fusion: a matched cohort analysis. Spine J. 2016;16(2):163-167.

24. D ePuy Synthes D. ViviGen Cellular Bone Matrix [technical monograph]. http:// synthes.vo.llnwd.net/o16/LLNWMB8/ US%20Mobile/Synthes%20North%20 America/Product%20Support%20 Materials/Technique%20Guides/ ViviGen_TechMono_8_single.pdf 25. E lgafy H, Wetzell B, Gillette M, et al.

Lumbar spine fusion outcomes using a cellular bone allograft with lineage-committed bone-forming cells in 96 patients.

BMC Musculoskelet Disord. 2021;22:699.

26. H all JF, McLean JB, Jones SM, Moore MA, Nicholson MD, Dorsch KA. Multilevel instrumented posterolateral lumbar spine fusion with an allogeneic cellular bone graft. J Orthop Surg Res. 2019;14:372.

27. Gibson AW, Feroze AH, Greil ME, et al.

Cellular allograft for multilevel standalone anterior cervical discectomy and fusion. Neurosurg Focus. 2021;50(6):E7.

28. D arveau SC, Leary OP, Persad-Paisley EM, et al. Existing clinical evidence on the use of cellular bone matrix grafts in spinal fusion: updated systematic review of the literature. Neurosurg Focus. 2021;50(6):E12.

19. ACE Surgical Supply Company. Osteocel Plus. https://www.acesurgical. com/osteocel-cellular-bone-matrix 20. Eastlack RK, Garfin SR, Brown CR, Meyer SC. Osteocel plus cellular allograft in anterior cervical discectomy and fusion: evaluation of clinical and radiographic outcomes from a prospective multicenter study. Spine (Phila Pa 1976). 2014;39(22):E1331-E1337.

21. Tohmeh AG, Watson B, Tohmeh M, Zielinski XJ. Allograft cellular bone matrix in extreme lateral interbody fusion: preliminary radiographic and clinical outcomes.

ScientificWorldJournal. 2012;2012:263637.

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From UCI Health in Orange County, California

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27

Platelet Rich Plasma in Spinal Disorders Low back pain (LBP) is one of the most common causes of disability worldwide.

Studies have shown that LBP is associated with lumbar disc degeneration.1 The progression of intervertebral disc degeneration is known to lead to tears within the annulus fibrosis. Because of an absence of a robust blood supply, the intervertebral tissues have little potential for self-repair. Tears within the posterior annulus fibrosus have been referred to as high-intensity zones (HIZs) as they are viewed as high-intensity signals on T2-weighted magnetic resonance imaging.

There are many studies that report that HIZs have been identified in as many as 28% to 59% of symptomatic LBP patients.1-3 Platelet-rich plasma (PRP) is an autologous blood concentrate that contains a natu-

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ral concentration of autologous growth factors and cytokines.

PRP has been used clinically for tissue regeneration and repair, demonstrating the ability to repair injured tissues, including tendons, ligaments, and cartilage, Yu-Po Lee, MD all of which have a low intrinsic healing potential. Because activated platelets can release more than several thousand bioactive proteins, it is believed that these concentrates have multiple important healing molecular functions relating to inflammation, angiogenesis, cell migration, and metabolism for tissue repair and regeneration.

A review of the in vitro effects of PRP on intervertebral disc cells shows that PRP has both anabolic and anti-inf lammatory ef-

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fects.4,5 Additionally, the anti-inflammatory properties of PRP are associated with its inhibitory effects on the nuclear factor-κ B (NF-κ B) signaling pathway in multiple cell type.4,5 Furthermore, bioactive molecules released from PRP may play a modulatory role encouraging cells to induce and secrete healing and biologically active molecules.

In clinical studies of PRP for LBP, results appear to be promising, demonstrating intradiscal injection effective for pain reduction.6,7 The first study to evaluate the safety and efficacy of intradiscal injections using PRP for discogenic LBP was reported by Akeda et al in 2011.6 The authors observed that visual analog scale and Roland-Morris Disability Questionnaire scores were significantly decreased at 1 month and that pain reduction was maintained at 6-month follow-up.6 In another study, Bodor et al7 performed intradiscal PRP injections for 47 thoracic or

lumbar discs in 35 patients. Most patients reported improvement in LBP at 1 week with pain relief maintained at 2 months.

The first double-blind randomized controlled trial was conducted by Tuakli-Wosornu et al. 8 At 8-week follow-up, patients in t he PRP group reported statistically sig n if ica nt i mprovements i n NRS best pain, functional rating index, and patient satisfaction in comparison to the control group. Among the PRP patients, 56% (15 of 27) were satisfied with the treatment, whereas only 18% of control patients (3 of 17) were satisfied.

While the use of PRP injections for discogenic pain holds promise, more non– industry-sponsored randomized clinical studies are needed to better understand its mechanism of action and long-term clinical outcome profile to better assess the suitability of this treatment modality. n

References 1. Peng B, Hou S, Wu W, Zhang C, Yang Y. The pathogenesis and clinical significance of a high-intensity zone (HIZ) of lumbar intervertebral disc on MR imaging in the patient with discogenic low back pain. Eur Spine J. 2006;15(5):583-587.

2. Peng B, Wu W, Hou S, Li P, Zhang C, Yang Y. The pathogenesis of discogenic low back pain. J Bone Joint Surg Br. 2005;87(1):62-67.

3. Dongfeng R, Hou S, Wu W, et al. The expression of tumor necrosis factor-α and CD68 in high-intensity zone of lumbar intervertebral disc on magnetic resonance image in the patients with low back pain. Spine. 2011;36(6):E429-E433.

4. Andia I, Maffulli N. Platelet-rich plasma for managing pain and inflam-

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mation in osteoarthritis. Nat Rev Rheumatol. 2013;9(12):721-730.

5. Andia I, Abate M. Platelet-rich plasma: combinational treatment modalities for musculoskeletal conditions.

Front Med. 2018;12(2):139-152.

6. Akeda K, Imanishi T, Ohishi K, et al.

Intradiscal injection of autologous serum isolated from platelet-rich-plasma for the treatment of discogenic low back pain: preliminary prospective clinical trial. Poster presented at the International Society for the Study of the Lumbar Spine meeting; June 14-18, 2011; Gothenburg, Sweden.

eds. Platelet-Rich Plasma: Regenerative Medicine: Sports Medicine, Orthopedic, and Recovery of Musculoskeletal Injuries.

Springer Berlin Heidelberg; 2014:265-279.

8. Tuakli-Wosornu YA, Terry A, Boachie-Adjei K, et al. Lumbar intradiskal platelet-rich plasma (PRP) injections: a prospective, double-blind, randomized controlled study. PM R. 2016;8(1):1–10.

7. Bodor M, Toy A, Aufiero D. Disc regeneration with platelets and growth factors.

In: Lana JFSD, Andrade Santana MH, Dias Belangero W, Malheiros Luzo AC,

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