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Augmented Reality: Transforming the Future of Spine Surgery

International Society for the Advancement of Spine Surgery

Evaluating Cervical Alignment Return to Activity Following Cervical Disc Arthroplasty A Comparative Review of Lumbar Bone Density Measurement Techniques and Additional Applications Update on Vertebral Augmentation for Thoracolumbar Fragility Fractures An Update on Multimodal Analgesia: Are We Better at Managing Postoperative Pain?

Intradiscal Injections: Is There Evidence to Support It?

PLUS

Ocular Complications in Spine Surgery

FA L L 20 23

AI-Driven Risk Stratification in Spine Surgery

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EDITORIAL Ocular Complications in Spine Surgery

ARTIFICIAL INTELLIGENCE AI-Driven Risk Stratification in Spine Surgery

Editor in Chief

NEW TECHNOLOGY

Kern Singh, MD

Augmented Reality: Transforming the Future of Spine Surgery

Editorial Board

CERVICAL SPINE

Brandon Hirsch, MD

Evaluating Cervical Alignment

Sravisht Iyer, MD

PATIENT OUTCOMES Return to Activity Following Cervical Disc Arthroplasty

BONE QUALITY A Comparative Review of Lumbar Bone Density Measurement Techniques and Additional Applications

Peter Derman, MD, MBA

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

FRACTURE Update on Vertebral Augmentation for Thoracolumbar Fragility Fractures

PAIN MANAGEMENT An Update on Multimodal Analgesia: Are We Better at Managing Postoperative Pain?

PAIN MANAGEMENT Intradiscal Injections: Is There Evidence to Support It?

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Vertebral Columns is published quarterly by the International Society for the Advancement of Spine Surgery. ©2023 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-2023

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EDITORIAL

From the Department of Orthopaedic Surgery, Rush University Medical Center, in Chicago, Illinois.

Ocular Complications in Spine Surgery Visual perception is initiated as light reaches the cornea, a transparent structure continuous with the sclera. Incoming light is focused by the lens onto the retina, a neural tissue lined with photoreceptors that transduces visual stimuli into electrochemical signals.

These signals then track posteriorly into the occipital lobe of the brain via the optic nerve to render visual perception. Although ocular complications are rare, they are increasingly being reported across several surgical fields, including orthopaedic, cardiothoracic, and general surgery.1–4 In 1948, Slocum et al documented the first spine surgery–linked case of blindness, which occurred as a result of incorrect intraoperative head positioning. 5 Over the past few decades, the complexity and number of spine surgeries has increased in the United States.6 According to a study from the Scoliosis Research Society, the frequency of eye complications is 1 per every 100 spinal procedures.7 Visual complications after spinal surgery can potentially bring about additional severe adverse postoperative outcomes for patients. Within spine surgery, perioperative vision loss (POVL) rates have been reported around 0.14% for lumbar fusion procedures and 0.28% for deformity correction cases. Individual patient characteristics such as preexisting health conditions, including hypertension, diabetes mellitus, and peripheral vascular disease or lifestyle

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Andrea M. Roca, MS

choices, such as smoking, may potentially increase the risk of experiencing POVL.7 Fatima N. Anwar, BA Complications POVL and central retinal artery occlusion (CRAO) are 2 of the most feared surgical complications by both patients and physicians because they often Alexandra C. Loya, BS culminate in visual field loss or irreversible blindness. However, corneal abrasion is the most commonly reported ocular complication.8,9 A corneal abrasion occurs when the epithelial layer Srinath S. Medakkar, BS of the cornea is separated from the underlying basement membrane. Corneal abrasions are generally classified by location, extent, and depth of the epitheRicha Singh, MD lial defect.9 Other less reported ocular complications include conjunctivitis, direct trauma, or chemical injury.

Neurological origins for vision loss after surgery are also reportKern Singh, MD ed. Posterior reversible encephalopathy syndrome (PRES) is a neurological condition characterized by symptoms like seizures, vision disturbances, headaches, and a reduced level of alertness. While it is

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more commonly associated with the field of obstetrics, cases of PRES have been documented in the field of orthopedics following procedures such as lumbar fusion.10 In these cases, causes have been associated with rapid spikes in blood pressure that surpass the brain’s self-regulating capacity, which eventually culminates in brain swelling.

However, experiencing recovery from PRES is much more likely in comparison to CRAO or other complications like ischemic optic neuropathy (ION).11 The most significant ocular complication for patients undergoing spine surgery are those associated with blindness due to the drastic impact on the patient’s life. POVL can be attributed to various origins, including occipital lobe infarction resulting in cortical blindness, blockages in the central retinal artery or ophthalmic vein, and inadequate blood flow to the optic nerve resulting in ION.12,13 Individuals who required postoperative recovery in the hospital or who required high acuity care in an intensive care unit are at increased risk of experiencing

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vision loss.14 Of all surgical subspecialties, spine and cardiac surgery reportedly have higher than average rates of POVL. 8,14,15 In a cohort study by Hofer et al, individuals reporting perioperative ocular injury versus those without injury were associated with instrumentation procedures, decompression and fusion procedures, right lateral positioning, and surgery involving the lumbar spine.14,16 In the United States, CRAO occurs at an approximate rate of 1 per every 100,000 people, whereas following spinal surgery, it has been reported to be significantly higher at an estimated 1 per every 1000 people.17

Risk Factors Patient positioning during a surgical procedure significantly influences the risk of a patient experiencing POVL postoperatively.

Prone positioning increases the risk of ocular complications by upwards of 10-fold.4,14,18 This increase is a result of the periorbital region receiving more direct pressure in the prone position resulting in increased intraocular pressure and potential complications of physical trauma or ischemic injury due to CRAO.18 However, prone, lateral, and Trendelenburg positioning of a patient in surgery may result in corneal contact with various items or surfaces, thereby increasing the risk for corneal abrasions. 3,19,20 Additionally, gender has been suggested to significantly influence the risk of POVL after spinal fusion with a greater risk of occurrence in men than in women. Furthermore, individuals aged 50–64 years showed a heightened risk of ocular complications, thus adding age as another contributing factor. These findings

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are supported by a case series published by the American Society of Anesthesiologists from a POVL registry across multiple centers. 21–23 Additional risk factors include deliberate hypotension, excessive blood loss, or an operative time exceeding 7 hours.18

Diagnosis, Treatment, and Prevention The most reported symptoms of those experiencing ocular complications include complaints of blurry vision, swelling, and pain around the eye. Patients experiencing any symptoms should be urgently referred for an ophthalmologic consultation.24 Up to 80% of patients with corneal abrasion present without evidence of trauma, leading to the conclusion that despite taping of the eyelids, approximately 59% of patients do not experience complete closure of the eyelids—an occurrence called lagophthalmos.18,25 One cause for intraoperative lagophthalmos and consequential corneal abrasions has been suggested to be a potential result of the frequent checks of the depth of anesthesia sedation in which the patient’s eyelids are lifted and assessed with reactive pupil testing.26 Should a corneal abrasion occur during surgery, the most reliable method to confirm the diagnosis is using fluorescein staining.8,9 The most effective protective measure against corneal abrasions remains intraoperative eyelid taping, but alternative protective measures include the use of ointments or cushioned pads over the eyes.27,26 ION typically presents as an abrupt, yet painless, loss of vision in one or more visual fields. The neuropathy can originate on the anterior or posterior aspect of the optic nerve based on the location of

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injury. ION often results in partial vision loss in both eyes or total blindness in more severe incidences. Diagnoses resulting from ION are typically detected after the patient wakes up after surgery.29 CRAO during spine fusion surgery can be prevented by protecting eyes from compression.13 In the operating room, placing the surgical table in a 5° reverse Trendelenburg position helps to decreased intraocular pressure in comparison to traditional prone positioning for surgery times shorter than 120 minutes.30 Hofer et al noted that patients with optic nerve ischemia were older, underwent longer operations, experienced more blood loss, and received more crystalloid fluids.14 Prevention of postoperative hypotension or hypovolemia leading to POVL may be accomplished through the use of fluid replacement in which colloid solution is substituted for crystalloid solution.17 It is recommended that high-risk patients undergo an eye examination of visual fields and pupillary reflexes as they regain consciousness after surgery.13

Conclusion The intricate and crucial process of visual perception is susceptible to several perioperative complications ranging from the most reported corneal abrasions to more severe consequences such as POVL and CRAO. It is imperative that healthcare professionals in the spinal field are educated regarding the risks for ocular injury during surgery. In prioritizing this vital education, healthcare professionals can avoid serious consequences such as irreversible blindness. The most prudent recommendation when suspecting an

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ocular complication is the immediate referral for ophthalmologic consultation. However, the best strategy centers on prevention, such as ensuring effective intraoperative eyelid

taping, reducing operative time, limiting prone positioning, and optimizing surgical table positions to decrease intraocular pressure. l

References 1. Su AW, Lin SC, Larson A N. Perioperative vision loss in spine surgery and other orthopaedic procedures. J Am Acad Orthop Surg. 2016;24:702–710.

2. Yu HD, Chou AH, Yang MW, Chang CJ. An analysis of perioperative eye injuries after nonocular surgery. Acta Anaesthesiol Taiwan. 2010;48:122–129.

3. Roth S, Thisted RA, Erickson JP, Black S, Schreider BD. Eye injuries after nonocular surgery. A study of 60,965 anesthetics from 1988 to 1992.

Anesthesiology. 1996;85:1020–1027.

4. Li A, Swinney C, Veeravagu A, Bhatti I, Ratliff J. Postoperative visual loss following lumbar spine surgery: a review of risk factors by diagnosis.

World Neurosurg. 2015;84:2010–2021.

5. Slocum HC, O’Neal KC Allen CR. Neurovascular complications from malposition on the operating table.

Surg Gynecol Obstet. 1948;86:729–734.

6. Rajaee SS, Bae HW, Kanim LEA, Delamarter RB. Spinal fusion in the United States: analysis of trends from 1998 to 2008. Spine. 2012;37:67–76.

7. Myers MA, Hamilton SR, Bogosian AJ, Smith CH, Wagner TA. Visual loss as a complication of spine surgery. A review of 37 cases. Spine. 1997;22:1325–1329.

8. Baig MN, Lubow M, Immesoete P, Bergese SD, Hamdy EA, Mendel E. Vision loss after spine surgery: review of the literature and recommendations. Neurosurg Focus. 2007;23:E15.

9. Moos DD, Lind DM. Detection and treatment of perioperative corneal abrasions. J Perianesth Nurs. 2006;21:332–338.

10. Yi JH, Ha SH, Kim YK, Choi EM. Posterior reversible encephalopathy syndrome in an untreated hypertensive patient after spinal surgery under general anesthesia—a case report.

Korean J Anesthesiol. 2011;60:369–372.

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11. Nickels TJ, Manlapaz MR, Farag E. Perioperative visual loss after spine surgery. World J Orthop. 2014;5:100–106.

12. Grover V, Jangra K. Perioperative vision loss: a complication to watch out. J Anaesthesiol Clin Pharmacol. 2012;28:11–16.

13. Roth S, Moss HE, Vajaranant TS, Sweitzer B. Perioperative care of the patient with eye pathologies undergoing nonocular surgery. Anesthesiology. 2022;137:620–643.

14. Hofer RE, Evans KD, Warner MA. Ocular injury during spine surgery.

Can J Anaesth. 2019;66:772–780.

15. Stevens WR, Glazer PA, Kelley SD, Lietman TM, Bradford DS. Ophthalmic complications after spinal surgery. Spine. 1997;22:1319–1324.

16. Ho VTG, Newman NJ, Song S, Ksiazek S, Roth S. Ischemic optic neuropathy following spine surgery. J Neurosurg Anesthesiol. 2005;17:38–44.

17. Patil CG, Lad EM, Lad SP, Ho C, Boakye M. Visual loss after spine surgery: a population-based study.

Spine. 2008;33:1491–1496.

18. Stambough JL, Dolan D, Werner R, Godfrey E. Ophthalmologic complications associated with prone positioning in spine surgery. J Am Acad Orthop Surg. 2007;15:156–165.

19. Lee SH, Chung I, Choi DS, et al. Visual loss due to optic nerve infarction and central retinal artery occlusion after spine surgery in the prone position: a case report. Medicine. 2017;96:e7379.

20. Xiong J, Liang G, Hu L, et al. Transient visual acuity loss after spine surgery in the prone position: a case report and literature review. J Int Med Res. 2020;48:300060520952279.

21. Postoperative Visual Loss Study Group.

Risk factors associated with ischemic optic neuropathy after spinal fusion sur-

gery. Anesthesiology. 2012;116:15–24.

22. Lee LA, Roth S, Posner KL, et al.

The American Society of Anesthesiologists Postoperative Visual Loss Registry: analysis of 93 spine surgery cases with postoperative visual loss.

Anesthesiology. 2006;105:652–659.

23. Holy SE, Tsai JH, McAllister RK, Smith KH. Perioperative ischemic optic neuropathy: a case control analysis of 126,666 surgical procedures at a single institution. Anesthesiology. 2009;110:246–253.

24. Hoff JM, Varhaug P, Midelfart A, Lund-Johansen M. Acute visual loss after spinal surgery. Acta Ophthalmol. 2010;88:490–492.

25. Kaye AD, Renschler JS, Cramer KD, et al. Postoperative management of corneal abrasions and clinical implications: a comprehensive review. Curr Pain Headache Rep. 2019;23:48.

26. Yanagidate F, Dohi S. Corneal abrasion after the wake-up test in spinal surgery. J Anesth. 2003;17:211–212.

27. Grixti A, Sadri M, Watts MT. Corneal protection during general anesthesia for nonocular surgery.

Ocul Surf. 2013;11:109–118.

28. Miller NR. Current concepts in the diagnosis, pathogenesis, and management of nonarteritic anterior ischemic optic neuropathy. J Neuroophthalmol. 2011;31:e1–e3.

29. Hayreh SS. Ischemic optic neuropathies—where are we now?

Graefes Arch Clin Exp Ophthalmol. 2013;251:1873–1884.

30. Carey TW, Shaw KA, Weber ML, DeVine JG. Effect of the degree of reverse Trendelenburg position on intraocular pressure during prone spine surgery: a randomized controlled trial. Spine J. 2014;14:2118–2126.

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

ARTIFICIAL INTELLIGENCE

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AI-Driven Risk Stratification in Spine Surgery Myles R.J. Allen, MBChB

Artificial Intelligence (AI) is a broad field of machine-driven problem-solving, data analysis, and pattern recognition, which aims to mimic traditionally human cognition.1 As a subset of AI, machine learning is focused on simulating human processing mechanisms using data input and algorithms, which formulate specialized systems that can predict specific outcomes.1,2 Since its development in the 1950s, AI has rapidly expanded our knowledge and resources to better understand the world by sifting through large volumes of data to identify patterns and outliers and solve difficult problems.1 The widespread availability of AI systems such as Chatsonic or ChatGPT has allowed the public to incorporate AI into everyday life, including AI-powered assistants, fraud protection, personalized learning, and autonomous vehicles. These systems are typically used as an enhancement tool of skilled professionals, rather than a replacement of human workf low. As an adaptable and available tool, its use increases efficiency by increasing productivity, reducing time and capital expenditure, and provides information for a plethora of areas such as economic, social, and governmental structures. 3 As AI rapidly advances, many professionals show concern regarding its future applications and the possibility of the outright replacement of human labor. While these

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concerns are valid, we aim to reinforce the grand benefits of utilizing AI as an advancement tool regarding risk stratification in spine surgery.

Ashley Yeo Eun Kim, BA

Conventional vs AI Risk Stratification Spine surgery risk assessment remains challenging. ConvenOlivia C. Tuma, BS tionally, multiple risk assessment tools have been validated using patient factors and comorbidities.

Certain metrics, including the American Society of Anesthesiologists classification, modified Tomoyuki Asada, MD Charlson Comorbidit y Index, and modified Frailty Index, have been retrospectively identified as important contributors for predicting surgical risks.4-6 However, these tools vary in accuracy Sravisht Iyer, MD and clinical applicability. For instance, Pulido et al demonstrated that adverse events can be predicted by the Modified Frailty Index, yet Lakomkin et al ascertained contrasting results.4,5 Additionally, Lakomkin et al established that the Charlson Comorbidity Index demonstrated superior predictive capacity over the Modified Frailty Index, but it could be used to predict mortality and length of

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hospital stay. 5 While some established clinical guidelines and existing risk calculators, such as the American College of Surgeons National Surgery Quality Improvement Program (ACS NSQIP) Surgical Risk Calculator, may help guide treatment decisions, risk stratification heavily relies on the expertise of the spine surgeon. Furthermore, although preoperative metrics provide valuable insights, these may be limited by human biases and a lack of adaptability.

Recently, AI-driven risk calculators have been developed as an alternative to these traditional risk stratification assessment tools and have been shown to have a greater effect toward improving patient outcomes over conventional risk stratification methods.7 Machine-learning algorithms, including decision trees and support vector machines, can analyze extensive datasets, including radiographical imaging, to identify patterns and risk factors that are often not observable by humans.8,9 This approach evaluates pre-established input and output variables to predict the outcome variable(s) from patients with similar input data.9 These novel algorithms can also “learn” to adapt and improve using additional patient data or patient variables to improve their reliability in determining precise risk assessments and surgical candidacy.7 Arvind et al demonstrated that machine learning outperformed more conventional risk stratification tools, including the American Society of Anesthesiologists classification, in predicting surgical complications for anterior cervical discectomy and fusion patients (p < 0.05).10 However, the reliability of these algorithms entirely depends on the reliabil-

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ity of the incorporated dataset and differed between algorithms.10,11

Use of AI in Risk Stratification AI risk stratification can occur throughout each stage of a patient’s journey—preoperatively, intraoperatively, and postoperatively—and may also assist in the location and grading of spinal pathology at the time of diagnosis.12 Decision trees are widely utilized predictive models that support clinician decision-making, typically toward identifying the optimal management method for specific patients.13 Their use has been demonstrated to be an effective and accurate tool to determine the optimal management method in spinal cord injuries14 and the risk classification of curve progression in scoliosis.15 By supplementing the decision-making process, clinicians spend less time determining management options, thus increasing workflow efficiency.12 Similar models may also be used to identify optimal surgical candidates and to highlight modifications in surgical approach to further benefit patient outcomes.

Examples include prediction models that identify the surgical intervention with the greatest success rate and lowest risk of patient complications in adult spinal deformity patients,16 models which predict failure risk in the holding power of pedicle screws in lumbar fusion,17 and prediction of nonhome discharge following elective anterior cervical discectomy and fusion.18 Along with AI, navigation and robotics have also become a frequently incorporated tool within spinal surgery.19 It is expected that AI, navigation,

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and robotics are likely to amalgamate to increase surgical accuracy, minimize iatrogenic complications, and improve patient postoperative outcomes by accounting for patient anatomical variations.19,20 A I predict ive models can be ut ilized preoperatively to assess patients’ perioperative complication risk before undergoing surgery. Shah et al successfully developed the first predictive risk calculator for C5 nerve root palsy after instrumented cervical fusion. 21 In separate studies, Karhade et al devised algorithms that accurately predict mortality in patients with spinal epidural abscesses and those with spinal metastatic disease. 22,23 Moreover, they also developed a predictive algorithm to identify patients at risk of prolonged postoperative opioid

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use after lumbar disc herniation surgery.24 Assessing risks preoperatively allows for tailored patient care aimed at minimizing potential complications. Furthermore, when surgical eligibility is unclear, AI can offer additional insights to assist surgeons in making informed decisions.

The benefit of AI in spine surgery is evident. However, it is still in the early stages of development. AI can be used as a clinician’s aid to improve patient care through risk stratification but is certainly not suitable to replace the clinician. If used effectively, AI reduces surgeon workload, freeing the surgeon to have more operative time. Subsequently, AI improves the surgical team’s efficiency, allowing more patients with spinal pathology to be treated and reducing healthcare

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expenditure without compromising patient care.19 Despite this, AI risk stratification has its limitations. Initially, AI models require a large dataset to be trained and validated, which takes considerable time and labor.

Additionally, these datasets are typically institution specific. Therefore, while the model may be effective, its benefit may not be transferable when incorporated to different patient populations.

To overcome this limitation, compilation of patient data between institutions must take place to prevent the overfitting of relatively small datasets and to prevent risk stratification and treatment recommendation bias.8,25,26 However, patient data privacy regarding the distribution of confidential patient information are great security concerns.

Therefore, methods that can accomplish this safely must be implemented. Furthermore, developed models require external validation to establish their bias, calibration, and overall clinical application before being employed to an independent patient population from another institution.23,27,28 Despite this, external validation of institution-specific models is sparse, further limiting their widespread clinical application.23 Groot et al found that most predictive machine-learning models lack external validation. 29 Hence, collaboration among institutions and validation from external sources are crucial for the advancement of AI in spine surgery.

Furthermore, AI use in spinal surgery is still in the early stages of development and will take considerable time before being implemented further. Nonetheless, even at the current developmental stage, spinal

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surgeons are likely to trust AI risk prediction models and believe that its use will be integrated within half a decade. 30 However, AI and ML advancement is occurring at a greater rate than the generational turnover of orthopedic surgeons.8 Therefore, orthopedic surgeons are required to continuously educate themselves throughout their career to maximize the benefit of this technology.8 Moreover, while many professionals fear the possibility that AI will replace their job, most orthopedic surgeons do not have this belief because of the vital doctor-patient relationship.31 Accordingly, while AI is superior in evaluating medical datasets, it can only evaluate the inputted measured variables; in contrast, surgeons are able to evaluate a patient’s medical history and social and personal factors through surgical consultations; therefore, they are able to take all aspects of a patient’s pathology into consideration.

Conclusion Artificial intelligence has enormous potential to reform spinal surgery care and patient optimization. Although AI use in spinal surgery is relatively new, it has been shown to be an effective tool in preoperative workup, patient selection, outcome prediction, and perioperative assistance. AI-driven decision support tools offer a promising avenue for more accurate, personalized, and scalable risk assessments with the potential to enhance patient outcomes and surgical decision-making. However, as AI develops, one must consider the large patient dataset needed for universal use and the data privacy and security risks during development. l

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References 1. IBM. What is artificial intelligence (AI)? https://www.ibm. com/topics/artificial-intelligence.

Accessed October 3, 2023.

2. Sidey-Gibbons JAM, Sidey-Gibbons CJ. Machine learning in medicine: a practical introduction. BMC Med Res Methodol. 2019;19(1):64.

3. Howard J. Artificial intelligence: implications for the future of work.

Am J Ind Med. 2019;62(11):917-926.

4. Pulido LC, Meyer M, Reinhard J, et al. Hospital frailty risk score predicts adverse events in spine surgery. Eur Spine J. 2022;31:1621-9.

5. Lakomkin N, Zuckerman SL, Stannard B, et al. Preoperative risk stratification in spine tumor surgery: a comparison of the modified Charlson Index, Frailty Index, and ASA score. Spine (Phila Pa 1976). 2019;44:E782-e7.

6. Veeravagu A, Li A, Swinney C, et al. Predicting complication risk in spine surgery: a prospective analysis of a novel risk assessment tool.

J Neurosurg Spine. 2017;27:81-91.

7. Hornung AL, Hornung CM, Mallow GM, et al. Artificial intelligence in spine care: current applications and future utility.

Eur Spine J. 2022;31(8):2057-2081.

8. Browd SR, Park C, Donoho DA. Potential applications of artificial intelligence and machine learning in spine surgery across the continuum of care.

Int J Spine Surg. 2023;17:S26-S33.

9. Lee NJ, Lombardi JM, Lehman RA. Artificial intelligence and machine learning applications in spine surgery.

Int J Spine Surg. 2023;17(S1):S18-S25.

10. Arvind V, Kim JS, Oermann EK, Kaji D, Cho SK. Predicting surgical complications in adult patients undergoing anterior cervical discectomy and fusion using machine learning.

Neurospine. 2018;15(4):329-337.

11. Yagi M, Yamanouchi K, Fujita N, Funao H, Ebata S. Revolutionizing spinal care: current applications and future directions of artificial intelligence and machine learning.

J Clin Med. 2023;12(13):4188.

12. Han Z, Wei B, Leung S, Nachum IB, Laidley D, Li S. Automated pathogenesis-based diagnosis of lumbar

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neural foraminal stenosis via deep multiscale multitask learning. Neuroinformatics. 2018;16(3-4):325-337.

13. Zhou S, Zhou F, Sun Y, et al. The application of artificial intelligence in spine surgery. Front Surg. 2022;9:885599.

14. Agarwal N, Aabedi AA, Torres-Espin A, et al. Decision tree-based machine learning analysis of intraoperative vasopressor use to optimize neurological improvement in acute spinal cord injury. Neurosurg Focus. 2022;52(4):E9.

15. Komeili A, Westover L, Parent EC, El-Rich M, Adeeb S. Monitoring for idiopathic scoliosis curve progression using surface topography asymmetry analysis of the torso in adolescents. Spine J. 2015;15(4):743-751.

16. Ames CP, Smith JS, Pellisé F, et al; European Spine Study Group, International Spine Study Group. Artificial intelligence based hierarchical clustering of patient types and intervention categories in adult spinal deformity surgery: towards a new classification scheme that predicts quality and value. Spine (Phila Pa 1976). 2019;44(13):915-926.

17. Varghese V, Krishnan V, Kumar GS. Evaluating pedicle-screw instrumentation using decision-tree analysis based on pullout strength. Asian Spine J. 2018;12(4):611-621.

18. Geng EA, Gal JS, Kim JS, et al. Robust prediction of nonhome discharge following elective anterior cervical discectomy and fusion using explainable machine learning. Eur Spine J. 2023;32(6):2149-2156.

19. Rasouli JJ, Shao J, Neifert S, et al. Artificial intelligence and robotics in spine surgery. Global Spine J. 2021;11(4):556-564.

20. Kochanski RB, Lombardi JM, Laratta JL, Lehman RA, O’Toole JE. Image-guided navigation and robotics in spine surgery. Neurosurgery. 2019;84(6):1179-1189.

21. Shah AA, Devana SK, Lee C, et al.

A risk calculator for the prediction of C5 nerve root palsy after instrumented cervical fusion. World Neurosurg. 2022;166:e703-e710.

algorithms for prediction of mortality in spinal epidural abscess.

Spine J. 2019;19(12):1950-1959.

23. Karhade AV, Ahmed AK, Pennington Z, et al. External validation of the SORG 90-day and 1-year machine learning algorithms for survival in spinal metastatic disease. Spine J. 2020;20(1):14-21.

24. Karhade AV, Ogink PT, Thio Q, et al.

Development of machine learning algorithms for prediction of prolonged opioid prescription after surgery for lumbar disc herniation.

Spine J. 2019;19:1764-1771.

25. Alsoof D, McDonald CL, Kuris EO, et al.

Machine learning for the orthopaedic surgeon: uses and limitations. J Bone Joint Surg Am. 2022;104:1586-1594.

26. Katsuura Y, Colón LF, Perez AA, et al. A primer on the use of artificial intelligence in spine surgery.

Clin Spine Surg. 2021;34:316-21.

27. Steyerberg EW, Vergouwe Y. Towards better clinical prediction models: seven steps for development and an ABCD for validation.

Eur Heart J. 2014;35(29):1925-31.

28. Shah AA, Karhade AV, Groot OQ, et al. External validation of a predictive algorithm for in-hospital and 90-day mortality after spinal epidural abscess. Spine J. 2023;23(5):760-765.

29. Groot OQ, Bindels BJJ, Ogink PT, et al. Availability and reporting quality of external validations of machine-learning prediction models with orthopedic surgical outcomes: a systematic review.

Acta Orthop. 2021;92(4):385-393.

30. Lans A, Oosterhoff JHF, Groot OQ, Fourman MS. (2021). Machine learning driven tools in orthopaedics and spine surgery: hype or reality?

Applications and perception of 31 physician opinions. Seminars in Spine Surgery. 2021;33(2):100871. https:// doi.org/10.1016/j.semss.2021.100871.

31. Kamal AH, Zakaria OM, Majzoub RA, Nasir EWF. Artificial intelligence in orthopedics: a qualitative exploration of the surgeon perspective. Medicine (Baltimore). 2023;102(24):e34071.

22. Karhade AV, Shah AA, Bono CM, et al. Development of machine learning

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From The Ohio State University, Wexner Medical Center, in Columbus, Ohio.

Augmented Reality Transforming the Future of Spine Surgery

In the rapidly evolving field of medicine, augmented reality (AR) has emerged as a transformative technology that seamlessly integrates virtual images into the real world. When compared to virtual Hania Shahzad, MD reality (VR), which immerses users entirely in a synthetic virtual realm, and mixed/merged reality (MR),1 which represents a fusion of a virtual environment with haptic feedback through physical models, AR technology stands out as a compelling choice for Safdar N. Khan, MD applications in spine surgery.

AR offers real-time applications in surgical procedures, surpassing the primarily training-focused utilities of VR and MR in nonoperative settings.2 AR navigation in spine surgery delivers accuracy and enhances workflow compared to conventional navigation and freehand techniques. This is particularly crucial in spine surgeries, where precision is vital due to the proximity of the operative field to delicate neurovascular structures. AR support also improves surgical comfort, particularly in reoperations where anatomical landmarks are lacking. Additionally, AR-based patient registration reduces radiation exposure for both patients and medical staff. It also provides a safe platform for trainees to practice

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complex surgical procedures through stepby-step interactive learning, minimizing the risk of patient harm and achieving higher success rates with reduced tissue trauma.

Additionally, the collaborative nature of AR fosters multidisciplinary teamwork during surgery and facilitates global expertise expansion through telementorship. Moreover, its cost-effectiveness and adaptability make it a valuable tool for surgical training and practice, especially in resource-limited settings. 3–5

AR-Based Surgical Set-up An AR-based surgical procedure comprises three key components: patient registration, instrument tracking, and display (Figure 1). The radiological images of the patient’s anatomy are used to construct a 3-dimensional (3D) model using advanced software.

Patient registration involves aligning computer-generated images with the surgical area utilizing markers strategically positioned within the surgical field to maintain continuous tracking. The markers play a critical role in maintaining constant tracking of both the surgeon’s instruments and the patient’s anatomy. Markers ensure that the superimposed 3D images remain in the correct position and orientation, even as the instruments move. The display device allows the visualization of the holographs

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NEW TECHNOLOGY

during surgery. As the surgeon operates, the display overlays an image of the vertebral spine onto the surgeon’s operating field, which enables precise identification of the optimal trajectory for procedures, such as an accurate screw placement.6 Display devices offer a diverse range of user interfaces tailored to meet the distinct demands of spine surgical procedures.

These include monitor-based AR, in which a C-arm with embedded cameras displays real-time video with AR enhancements on an operating room monitor, head-mounted display AR (with AR integrated into surgeons’

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goggles), microscope AR (with predefined AR elements seen through the microscope), and projector-based AR (with holographic overlays on glass screens). Comparing these interfaces is complex due to differing study metrics. Selection depends on surgical needs and technological advancements.

Clinical Applications of AR in Spine Surgery AR technolog y has undergone extensive investigation in preclinical settings within the domain of spine surger y, ex hibiting significant potential to augment accuracy,

Figure 1: Schematic representation of augmented reality–based surgical set-up.

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safety, and training in this specialized field (Table). Investigations into clinical studies and live patients are painting an exciting picture of its potential benefits.6 The scrutiny surrounding the safety and efficacy of AR navigation in thoracic pedicle screw placement has yielded highly promising results. Researchers have achieved an overall accuracy rate of an impressive 94.1%, notable for its absence of severe errors or device-related adverse events.7,8 Of equal significance is the seamless integration of AR into hybrid operating room setups, marked by the inclusion of intraoperative imaging and patient tracking. This technological integration has successfully eliminated the necessity for traditional fluoroscopy, thereby not only mitigating radiation exposure but also substantially enhancing the precision of screw placement.9,10 Remarkably, the introduction of AR into the operating theater does not impede the efficiency of surgical procedures. AR-assisted spinal surgeries do not lengthen the duration of operations but, rather, they augment the density of pedicle screw placements, particularly in intricate deformity cases.9,10 The advantages of A R-assisted pedicle screw instrumentation continue to accumulate, with research indicating reduced intraoperative bleeding, shorter surgical durations, and notably superior patient-related outcomes compared to conventional methods.11 Moreover, meticulous fine-tuning of AR’s capabilities, including the optimization of an intraoperative holographic model pipeline, has resulted in pinpoint precision through the utilization of patient-specific

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landmarks.12 The synergy of intraoperative cone-beam computed tomography scans with AR-assisted systems has proven highly effective in identifying pedicle screw breaches,13 Table. Applications and Key Findings of Augmented Reality (AR) in Spine Surgery

Application and Key Findings Thoracic Pedicle Screw Placement • Overall accuracy: 94.1% with minimal errors or adverse events.

• Integration into hybrid operating rooms eliminates the need for fluoroscopy, reducing radiation exposure.

• AR-assisted surgeries maintain procedural efficiency and enhance screw placement density.

• AR-assisted pedicle screw instrumentation results in less bleeding, shorter surgeries, and improved patient outcomes.

• Fine-tuning of AR capabilities, including holographic model optimization, enhances precision.

• Integration with intraoperative cone-beam computed tomography scans identifies screw breaches, reducing radiation exposure.

Vertebroplasty • AR combined with artificial intelligence achieves accuracy comparable to fluoroscopy, with slightly longer trocar deployment.

• AR navigation significantly reduces fluoroscopy usage, shortening surgery and improving entry points.

Tumor Resection • Microscope-based AR aligns visible tumor outlines with AR visualization, enhancing precision.

• Integration of intraoperative computed tomography with AR reduces radiation exposure by 70%.

Osteotomies • Successful execution of osteotomies, restoring spinal posture.

• AR assistance achieves complex resection without breaching tumor capsules, ensuring safety.

Rod Bending • AR applications with Microsoft HoloLens enhance precision.

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rendering routine postoperative CT scans obsolete while simultaneously reducing the overall radiation exposure burden on both patients and medical staff. These findings collectively underscore the transformative potential of AR in the field of spine surgery, offering an intriguing glimpse into the future of precision, safety, and patient care in this specialized domain.

The dynamic combination of AR with artificial intelligence in vertebroplasties achieves accuracy on par with traditional fluoroscopy, albeit with a slight extension in trocar deployment time.14 Furthermore, AR-assisted navigation substantially reduces the reliance on fluoroscopy, thereby curtailing operative durations and significantly enhancing

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the proportion of “optimal” entry points.15 The introduction of a microscope-based AR navigation system into tumor resection surgery has illuminated a close alignment between the visible tumor outline and AR visualization. This alignment translates into a remarkable boost in surgical precision. The amalgamation of intraoperative computed tomography (CT) with AR has yielded a staggering 70% reduction in effective radiation exposure.16,17 The early pioneers of AR application in osteotomies, led by the work of Kosterhon et al, deserve commendation for laying the foundational groundwork.

They executed osteotomies in the thoracic and lumbar regions, restoring spinal posture with surgical finesse.18 Similarly, Molina et al

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executed a complex resection of a chordoma margin without breaching the tumor capsule.

Their posterior-only approach, bolstered by AR head-mounted displays and integrated tracking cameras, underlined the precision and safety offered by this pioneering technology.19 Additionally, AR applications employing Microsoft HoloLens head-mounted displays have unlocked a new level of precision, particularly in rod bending.20

Legal and Ethical Implications In terms of protecting data, new technologies pose new challenges that have both legal and ethical implications. 21 In general, the use of new technologies has opened new paths for fraud, scams, and data trading. A special threat is created using technologies that track cognitive or decision-making processes, or augmented intelligence, which gathers very personal data, for example, on the functioning of someone’s brain. In the United Kingdom, current legal requirements, including common law, the Data Protection Act 1998, and the Freedom of Information Act 2000, establish the framework for data protection and confidentiality. The holding organizations, such as hospitals, should have governing bodies or a designated “Caldicott guardian” responsible for enforcing data security and protecting personally identifiable data as highlighted by the General Medical Council. While regulations like the General Data Protection Regulation in the European Union serve as foundational pillars for data protection, they must be complemented by specific guidelines tailored to the unique challenges posed by AR technologies. Fur-

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thermore, the National Health Service (NHS) adheres to the NHS code of practice for confidentiality, which is underpinned by 7 principles governing the collection and transfer of identifiable information.22 Healthcare professionals engaging with patient data through AR technology must possess a deep understanding of these principles to ensure compliance.

Surgeon autonomy may be influenced by marketing efforts promoting AR, potentially impacting unbiased decision-making.

Patients, too, can be swayed by advertising, potentially influencing their choice of surgeons or facilities offering AR-assisted procedures and affecting their autonomy in healthcare decisions. Ensuring informed consent and transparency about AR’s role in surgery is paramount, alongside managing conflicts of interest that may arise from financial relationships between technology providers and healthcare professionals.

The development of these groundbreaking technologies has ignited concerns about the potential introduction of biases into their design and implementation, particularly when the development teams lack diversity.

Biases embedded within technology can have far-reaching consequences, disproportionately affecting specific user groups based on factors such as gender, race, age, or social background. 23

Future Directions To fully unlock AR’s potential in the field of spine surgery and facilitate its widespread adoption, it becomes imperative to prioritize aspects such as standardization of protocol

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and outcome measures, improving the ergonomics of AR headsets,24 forging ethical frameworks, and investing in comprehensive education and training programs. AR technology continues to redefine the boundaries

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of what can be achieved in the world of spine surgery, transcending its role as a mere tool and emerging as a transformative force that pushes boundaries and elevates the standards of precision, safety, and patient care. l

The authors extend their appreciation to Momna Kazmi for producing the graphics for Figure 1.

References 1. Yuk FJ, Maragkos GA, Sato K, Steinberger J. Current innovation in virtual and augmented reality in spine surgery.

Ann Transl Med. 2021;9(1):94.

2. Sakai D, Joyce K, Sugimoto M, et al. Augmented, virtual and mixed reality in spinal surgery: a real-world experience. J Orthop Surg.

2020;28(3):2309499020952698.

3. Shahzad H, Bhatti NS, Phillips FM, Khan SN. Applications of augmented reality in orthopaedic spine surgery. J Am Acad Orthop Surg. 2023;31(17):e601.

4. Cofano F, Di Perna G, Bozzaro M, et al.

Augmented reality in medical practice: from spine surgery to remote assistance. Front Surg. 2021;8:657901.

5. Carl B, Bopp M, Saß B, Voellger B, Nimsky C. Implementation of augmented reality support in spine surgery.

Eur Spine J. 2019;28(7):1697-1711.

6. Burström G, Persson O, Edström E, Elmi-Terander A. Augmented reality navigation in spine surgery: a systematic review. Acta Neurochir (Wien). 2021;163(3):843-852.

7. Elmi-Terander A, Burström G, Nachabe R, et al. Pedicle screw placement using augmented reality surgical navigation with intraoperative 3D imaging. Spine. 2019;44(7):517-525.

8. Molina CA, Sciubba DM, Greenberg JK, Khan M, Witham T. Clinical accuracy, technical precision, and workflow of the first in human use of an augmented-reality head-mounted display stereotactic navigation system for spine surgery.

Oper Neurosurg. 2021;20(3):300-309.

9. Elmi-Terander A, Burström G, Nachabé R, et al. Augmented reality navigation with intraoperative 3D imaging

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vs fluoroscopy-assisted free-hand surgery for spine fixation surgery: a matched-control study comparing accuracy. Sci Rep. 2020;10(1):707.

10. Edström E, Burström G, Nachabe R, Gerdhem P, Elmi Terander A. A novel augmented-reality-based surgical navigation system for spine surgery in a hybrid operating room: design, workflow, and clinical applications.

Oper Neurosurg. 2020;18(5):496-502.

11. Gu Y, Yao Q, Xu Y, Zhang H, Wei P, Wang L. A clinical application study of mixed reality technology assisted lumbar pedicle screws implantation.

Med Sci Monit Int Med J Exp Clin Res. 2020;26:e924982-1-e924982-12.

12. Buch VP, Mensah-Brown KG, Germi JW, et al. Development of an intraoperative pipeline for holographic mixed reality visualization during spinal fusion surgery. Surg Innov. 2021;28(4):427-437.

13. Burström G, Nachabe R, Persson O, Edström E, Elmi Terander A. Augmented and virtual reality instrument tracking for minimally invasive spine surgery: a feasibility and accuracy study. Spine. 2019;44(15):1097.

14. Auloge P, Cazzato RL, Ramamurthy N, et al. Augmented reality and artificial intelligence-based navigation during percutaneous vertebroplasty: a pilot randomised clinical trial. Eur Spine J. 2020;29(7):1580-1589.

15. Hu MH, Chiang CC, Wang ML, Wu NY, Lee PY. Clinical feasibility of the augmented reality computer-assisted spine surgery system for percutaneous vertebroplasty. Eur Spine J. 2020;29(7):1590-1596.

16. Carl B, Bopp M, Saß B, Nimsky C. Microscope-based augment-

ed reality in degenerative spine surgery: initial experience. World Neurosurg. 2019;128:e541-e551.

17. Carl B, Bopp M, Saß B, Pojskic M, Voellger B, Nimsky C. Spine surgery supported by augmented reality. Glob Spine J. 2020;10(2 suppl):41S-55S. 18. Kosterhon M, Gutenberg A, Kantelhardt SR, Archavlis E, Giese A. Navigation and image injection for control of bone removal and osteotomy planes in spine surgery. Oper Neurosurg (Hagerstown). 2017;13(2):297-304.

19. Molina CA, Dibble CF, Lo SFL, Witham T, Sciubba DM. Augmented reality– mediated stereotactic navigation for execution of en bloc lumbar spondylectomy osteotomies. J Neurosurg Spine. 2021;34(5):700-705.

20. Wanivenhaus F, Neuhaus C, Liebmann F, Roner S, Spirig JM, Farshad M. Augmented reality-assisted rod bending in spinal surgery.

Spine J. 2019;19(10):1687-1689.

21. Parsons TD. Ethical challenges of using virtual environments in the assessment and treatment of psychopathological disorders. J Clin Med. 2021;10(3):378.

22. Donaldson A, Walker P. Information governance—a view from the NHS. Int J Med Inf. 2004;73(3):281-284.

23. Wójcik M. Augmented intelligence technology. The ethical and practical problems of its implementation in libraries.

Libr Hi Tech. 2020;39(2):435-447.

24. McKnight RR, Pean CA, Buck JS, Hwang JS, Hsu JR, Pierrie SN. Virtual reality and augmented reality—translating surgical training into surgical technique. Curr Rev Musculoskelet Med. 2020;13(6):663-674.

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CERVICAL SPINE

From UCI Health in Orange County, California.

Evaluating Cervical Alignment The cervical spine is notable for its intricate complexity and holds the greatest range of motion in the entire spine while also offering robust support and stability for the head. However, Yu-Po Lee, MD the balance increases as people age, manifesting in degenerative changes affecting both the discs and the facet joints. These changes alter cervical spine alignment and can lead to pain.

Cervical spondylotic myelopathy is a degenerative condition of the cervical spine.

The prevalent hypothesis attributes such myelopathy to the onset of disc and facet joint degeneration that cause disc bulging and bone spurs that thus impinge on the spina l cord and ner ve roots. However, some recent studies suggest that cervical sag it ta l a l ig n ment ca n cause cer v ica l myelopathy. Evaniew et al performed a prospect ive study on 250 pat ients who presented with cervical myelopathy.1 The authors found that an increased cervical sagittal vertical axis (cSVA) measured from C2-7 and T1 slope were associated with inferior health-related qualit y of life at presentation among patients with CSM, but no significant associations were observed following surgical treatment. At 12 months after surger y, there were no significant associations between alignment parameters, changes in alignment, or shifts in health-related quality of life, function, or

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symptoms. This observation is echoed in additional research, such as the retrospective study by Lin et al, which reinforced the correlation between increased disability and alterations in cervical alignment parameters on 90 patients who had surgery for cervical spondylotic myelopathy. 2 The authors noted that the disability of the neck increased with increasing C2-C7 SVA and T1S-CL and decreasing cervical lordosis before surgical reconstruction.

Further research delves into the impact of cervical sagittal alignment on postoperative outcomes following cervical spine surgery.

Hyun et al performed a retrospective study on 38 patients who underwent posterior cer v ica l decompression and f usion for cervical myelopathy. 3 The authors found that disability of the neck increased with cervical sagittal malalignment after cervical spine surgery and that a greater T1S-CL mismatch was associated with a greater degree of cervical malalignment. Specifically, a mismatch greater than 26.1° corresponded to positive cervical sagittal malalignment, defined as C2-C7 SVA greater than 50 mm.

The evaluation of sagittal alignment of the cervical spine is determined by measuring the cer vical sagittal vertical axis (SVA), which is determined by measuring the distance between either the C2 or C7 plumb line, and using a vertical line drawn from the posterior superior corner of the sacrum. The cervical SVA (C2 SVA) has also be described

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as measuring the distance between a plumb line dropped from the center of C2 and the posterior superior aspect of C7 (C2–C7 SVA) (Figure 1A). Other measurements that can be evaluated include cervical lordosis (CL), T1 slope (T1S), neck tilt (NT) and thoracic inlet angle (TIA). Cervical lordosis can be determined by drawing a line perpendicular to the inferior endplate of C2 and a perpendicular line to the inferior endplate of C7.

The angle formed by these perpendicular lines forms what is referred to as cervical lordosis (Figure 1B). The T1 slope can be determined by drawing a horizontal line and another line along the superior end plate of T1 (Figure 1C). Neck tilt can be determined using the angle formed by a vertical line drawn from the tip of the sternum and the center of the upper end plate of the sternum with another line drawn from the center of the T1 upper end plate (Figure 1D).

In conclusion, the intricate anatomy of the cervical spine with advances in age increases its susceptibility to degenerative changes. The alteration in spine alignment underscores the need for accurate measurements to optimize surgical outcomes and enhance patient quality of life. Knowing these measurements are additional tools

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that spine surgeons can use to evaluate cervical alignment and improve a surgeon’s ability to diagnose cervical malalignment and thus improve outcomes. l

Figure 1. (A) Cervical C2 sagittal vertical axis (black line). (B) Cervical lordosis (light blue line). (C) T1 slope (orange line). (D) Neck tilt (red line).

References 1. Evaniew N, Charest-Morin R, Jacobs WB, et al; Canadian Spine Outcomes and Research Network (CSORN).

Cervical sagittal alignment in patients with cervical spondylotic myelopathy: an observational study from the Canadian Spine Outcomes and

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Research Network. Spine (Phila Pa 1976). 2022;47(5):E177-E186.

2. Lin T, Chen P, Wang Z, Chen G, Liu W. Does cervical sagittal balance affect the preoperative Neck Disability Index in patients With cervical myelopathy?

Clin Spine Surg. 2020;33(1):E21-E25.

3. Hyun SJ, Kim KJ, Jahng TA, Kim HJ. Relationship between T1 slope and cervical alignment following multilevel posterior cervical fusion surgery: impact of T1 slope minus cervical lordosis. Spine (Phila Pa 1976). 2016;41(7):E396-E402.

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

Return to Activity Following Cervical Disc Arthroplasty Chad Z. Simon, BS

Cer v ica l spondylosis is pr imarily t reated w it h t he gold standard anterior cervical discectomy and fusion (ACDF),1-3 Eric Mai, BS but over the past decade, cervical disc arthroplast y (CDA) has ga ined popu la r it y as a n anterior alternative.4 CDA can achieve symptomatic relief for 1- to 2-level mild-to-moderate Cole Kwas, BA degeneration while maintaining disc height, preserving motion, and reducing adjacent segment loading.5-6 Importantly, CDA has demonstrated similar or earlier unrestricted return to activities Tomoyuki Asada, MD (RTA) in the early postoperative period compared to ACDF, but the current body of evidence is still in its early stages.7 Young, ac t ive pat ient s wou ld l i kely desire and benefit from earlier Sheeraz A. Qureshi, MD, MBA RTA a nd t he reta i ned ra nge of motion (ROM),4,8 and spine surgeons should endeavor to elucidate the RTA timeline when recommending CDA. In the present article, we aim to clarif y RTA as it relates to work, sports, and multi-level constructs in order to assist t he spine surgeon in properly counseling art hroplast y candidates on postoperative outcomes.

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Return to Work As CDA continues to grow in its clinical applicability, most cases are being performed in patients from 40-54 years old. 9 Many patients within this age demographic find themselves in the middle of their working careers. As such, the ability to return to work (RTW) represents a critical indicator of surgical success for both patients and surgeons alike. Several randomized controlled trials have characterized RTW timelines for CDA and ACDF. Heller et al found significantly different median RTW intervals of 48 and 61 days for CDA with BRYAN Cervical Discs (Medtronic, Minneapolis, MN) and ACDF groups, respectively.10 Similarly, Cheng et al found that patients undergoing CDA with the BRYAN implant returned to work sooner after surgery compared to the ACDF group (20 vs 84 days).11 Mummaneni et al compared outcomes between CDA with the PRESTIGE Cervical Disc System (Medtronic, Minneapolis MN) and ACDF and found that patients in the CDA group returned to work 16 days sooner than those in the ACDF group (45 vs 61 days), but this finding was not statistically significant.12 The authors of these 3 studies suggested this difference may be due to better functional and neurological outcomes, retained preoperative ROM, and fewer adverse events in the early postoperative period. Differences in RTW for all

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subsequent timepoints through 120 months after surgery were not significant.10,13,14 Several retrospective studies have reported significant differences in RTW metrics between CDA and ACDF. Badve et al found t hat 49.2% of patients undergoing CDA with BRYAN implants returned to work by 6 weeks after the operation compared to 39.4% for the ACDF group, with similar rates between groups at 6 months and 2 years.15 Subramanian et al reported 90.9% of CDA patients returned to work in 14 days while 85.7% of ACDF patients returned to work in 16 days. The authors further noted that occupation intensity was associated with decreased odds of RTW by 15 days.7 When comparing outcomes of CDA in the ambulatory and hospital settings, Gornet et al found no significant differences in RTW timelines for patients between the ambulatory surgical center, hospital outpatient, and hospital inpatient settings.16 Receiving workers’ compensation benefits has been found to be associated with inferior outcomes following spine surgery.17-19 In the context of CDA, Gornet et al reported that patients receiving workers’ compensation required significantly more time to return to work compared to controls (145.2 vs 61.9 days), which may have been due to self-reported physical demands of the respective jobs.20 Steinmetz et al performed a subgroup analysis of workers’ compensation patients and reported that those undergoing CDA returned to work more quickly on average than those undergoing ACDF (101 vs 222 days), though the difference was not statistically significant. The difference in average

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RTW may have been due to decreased neck disability.21

Return to Sports The merits of CDA are distinguishable not only in the general population but also in athletes with the objective of returning to sports. For both noncompetitive and competitive athletes, return to sports (RTS) is considered a subjective measure that hinges upon personal goals and expectations. 22 Nevertheless, postoperative recovery time, preserved ROM, and success in returning

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to athletics are critical considerations for athletes undergoing surger y to address cervical pathology.23 Reinke et al found that athletes undergoing single-level CDA for disc herniation demonstrated no significant difference in pre-herniation and postoperative modified Tegner activity scores. Hence, these athletes were all able to return to athletics at a near-identical intensity compared to before injury. 24 In a systematic review of athletes undergoing CDA, Reiter et al found that all patients successfully RTS, on average restarting training and competition after 10.1 weeks and 30.5 weeks, respectively. These findings indicate a comparable or quicker RTS when compared to ACDF, posterior fusion, or nonsurgical management. 25 Like athletes, active-duty military personnel face rigorous physical demands and vertebral stresses.

Consequently, examining CDA outcomes in this population could be useful in optimizing treatment for athletes.25 Tumialán et al found that military personnel undergoing CDA returned to duty on average 6.2 weeks sooner than military personnel undergoing ACDF (10.3 vs 16.5 weeks, p = 0.008). 26 Maintenance of cervical ROM is impactful in return to athletics since athletes’ cervical spines tend to experience greater physical loading than the general population; as such, ROM limitations may substantially decrease performance.23,27 For ROM preservation, CDA appears to be the optimal motion-sparing treatment modality.28 In contrast to patients undergoing ACDF, patients undergoing CDA have been found to demonstrate significantly greater improvements in cervical ROM (+5.9° vs -0.8° in ACDF patients). 29

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Chang et al reported that loss of ROM at the operative level in ACDF patients results in compensation throughout the unfused cervical spine to maintain gross cervical mobility. In contrast, CDA patients maintained a physiologic distribution of ROM at 12-month follow-up, potentially reducing the risk of adjacent segment degeneration when compared to ACDF. 30 Considering that CDA is a relatively newer surgical treatment for cervical pathology, further research regarding long-term performance is warranted in physically active populations.31 Nonetheless, current evidence regarding the clinical and biomechanical advantages of CDA in athletes is encouraging.

Return to Activities for Multilevel Constructs In patients with multi-level degeneration other w ise w ithout contraindications, a multi-level CDA may be performed. Generally, these are 2-level procedures, though procedures involving more than 2 levels have been performed as well.11,32,33 In the study by Cheng et al, including 2- and 3-level CDAs, the author reported significantly earlier RTW for the CDA group compared to ACDF (20 vs 84 days).11 Huppert et al compared RTW status in a cohort of patients on preoperative sick leave and received either 1-level or 2-level CDA. At 2 years, 46% of the 2-level CDA group returned to work with 21% remaining on sick leave, while 70% of the 1-level returned and only 13% stayed on sick leave. The average time to return was longer for the 2-level group, though it was not statistically significant (7.5 vs. 4.8

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months, p = 0.079). Of note, the 2-level group had a significantly longer preoperative sick leave period at baseline (15.6 vs. 7.0 months), which may have impacted return to work.

At 2-year follow-up, both groups’ return to work statuses improved significantly compared to preoperatively. 34 In a young military population with high activity demand, Zarkadis et al found that 12 of 18 patients undergoing 2-level CDA were able to return to duty in 9.6 ± 11.7 weeks. All patients who returned were able to resume their previous roles with significant improvement in their pain scores compared to preoperatively. Six of the 18 did not return to duty and were medically retired. 35 At times, a CDA may be utilized in combination with an ACDF to produce a hybrid construct (eg, CDA at 1 level and ACDF at another a level). Cody et al investigated the RTA status of a mixed cohort of 1-level CDAs, 2-level CDAs, and multi-level hybrids. They found that 96.0% of the 2-level contiguous CDAs and 90.6% of the 2-level hybrids returned to activities and experienced complete symptomatic relief. In contrast, patients receiving 3-level hybrids fared worse as only

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72.2% returned to activities with 77.8% experiencing complete symptomatic relief. The authors attributed this difference to higher preoperative symptom severity than the 2-level groups with 27.8% vs 10% experiencing myelopathic symptoms, respectively. The study noted an average follow-up of approximately 11 months. 36 Though the literature on RTA for multi-level CDA constructs is limited, the impact of sparing ROM and fairly maintained natural forces on RTA appear to remain for constructs greater than 1 level.

Conclusion Patients with degenerative cervical disease who are candidates for CDA would benefit from understanding their timeline for RTA, especially since these patients are often younger and more active. Returning to work and sports appears to be in greater proportion and at earlier time points for CDA compared to ACDF. Although further studies are needed to understand RTA in CDA, especially in higher-activity populations and multi-level constructs, CDA is a promising intervention for patients to return to their normal daily activities. l

References 1. Bohlman HH, Emery SE, Goodfellow DB, Jones PK. Robinson anterior cervical discectomy and arthrodesis for cervical radiculopathy. Longterm follow-up of one hundred and twenty-two patients. J Bone Joint Surg Am. 1993;75(9):1298-1307.

2. Abraham DJ, Herkowitz HN. Indications and trends in use in cervical spinal fusions. Orthop Clin North Am. 1998;29(4):731-744.

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3. Epstein NE. A review of complication rates for anterior cervical diskectomy and fusion (ACDF).

Surg Neurol Int. 2019;10:100.

4. Paek S, Zelenty WD, Dodo Y, et al. Up to 10-year surveillance comparison of survivability in single-level cervical disc replacement versus anterior cervical discectomy and fusion in New York. J Neurosurg Spine. 2023;39(2):206-215.

5. Derman PB, Zigler JE. Cervical disc arthroplasty: rationale and history. Int J Spine Surg. 2020;14(s2):S5-S13.

6. Gornet MF, Burkus JK, Shaffrey ME, Argires PJ, Nian H, Harrell FE. Cervical disc arthroplasty with PRESTIGE LP disc versus anterior cervical discectomy and fusion: a prospective, multicenter investigational device exemption study. J Neurosurg Spine. 2015;23(5):558-573.

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References, continued 7. Subramanian T, Shinn D, Korsun M, et al. Recovery kinetics following cervical spine surgery. Spine (Phila Pa 1976). Published online September 19, 2023. https://doi. org/10.1097/BRS.0000000000004830 8. Gao X, Yang Y, Liu H, et al. A comparison of cervical disc arthroplasty and anterior cervical discectomy and fusion in patients with two-level cervical degenerative disc disease: 5-year follow-up results. World Neurosurg. 2019;122:e1083-e1089.

9. Leclercq P, Bisschops R. Optimizing outcomes with radiofrequency ablation of barrett’s esophagus: candidates, efficacy and durability. Gastrointest Endosc Clin N Am. 2021;31(1):131-154.

10. Heller JG, Sasso RC, Papadopoulos SM, et al. Comparison of BRYAN cervical disc arthroplasty with anterior cervical decompression and fusion: clinical and radiographic results of a randomized, controlled, clinical trial. Spine (Phila Pa 1976). 2009;34(2):101-107.

11. Cheng L, Nie L, Li M, Huo Y, Pan X. Superiority of the Bryan(®) disc prosthesis for cervical myelopathy: a randomized study with 3-year followup. Clin Orthop Relat Res. 2011;469(12):3408-3414.

12. Mummaneni PV, Burkus JK, Haid RW, Traynelis VC, Zdeblick TA. Clinical and radiographic analysis of cervical disc arthroplasty compared with allograft fusion: a randomized controlled clinical trial. J Neurosurg Spine. 2007;6(3):198-209.

13. Lavelle WF, Riew KD, Levi AD, Florman JE. Ten-year outcomes of cervical disc replacement with the BRYAN cervical disc: results from a prospective, randomized, controlled clinical trial. Spine (Phila Pa 1976). 2019;44(9):601-608.

14. Sasso RC, Anderson PA, Riew KD, Heller JG. Results of cervical arthroplasty compared with anterior discectomy and fusion: four-year clinical outcomes in a prospective, randomized controlled trial. J Bone Joint Surg Am. 2011;93(18):1684-1692.

15. Badve SA, Florman JE, Levi AD, Kurra S, Riew KD, Lavelle WF. Employment status for the first decade following randomization to cervical disc arthroplasty versus fusion. Spine (Phila

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Pa 1976). 2020;45(20):1411-1418.

16. Gornet MF, Buttermann GR, Wohns R, et al. Safety and efficiency of cervical disc arthroplasty in ambulatory surgery centers vs. hospital settings.

Int J Spine Surg. 2018;12(5):557-564.

17. Hani U, Monk SH, Pfortmiller D, et al. Effect of workers’ compensation status on pain, disability, quality of life, and return to work after anterior cervical discectomy and fusion: a 1-year propensity score-matched analysis. J Neurosurg Spine. Published online July 21, 2023. https:// doi.org/10.3171/2023.6.SPINE23217 18. Cha EDK, Lynch CP, Jacob KC, et al.

Workers’ compensation association with clinical outcomes after anterior cervical diskectomy and fusion.

Neurosurgery. 2022;90(3):322-328.

19. Harris I, Mulford J, Solomon M, van Gelder JM, Young J. Association between compensation status and outcome after surgery: a meta-analysis. JAMA. 2005;293(13):1644-1652.

20. Gornet MF, Schranck FW, Copay AG, Kopjar B. The effect of workers’ compensation status on outcomes of cervical disc arthroplasty: a prospective, comparative, observational study.

J Bone Joint Surg Am. 2016;98(2):93-99.

21. Steinmetz MP, Patel R, Traynelis V, Resnick DK, Anderson PA. Cervical disc arthroplasty compared with fusion in a workers’ compensation population.

Neurosurgery. 2008;63(4):741-747.

26. Tumialán LM, Ponton RP, Garvin A, Gluf WM. Arthroplasty in the military: a preliminary experience with ProDisc-C and ProDisc-L. Neurosurg Focus. 2010;28(5):E18.

27. Hsu WK. Outcomes following nonoperative and operative treatment for cervical disc herniations in National Football League athletes. Spine (Phila Pa 1976). 2011;36(10):800-805.

28. Puttlitz CM, Rousseau MA, Xu Z, et al. Intervertebral disc replacement maintains cervical spine kinetics. Spine (Phila Pa 1976). 2004;29(24):2809-2814.

29. Auerbach JD, Anakwenze OA, Milby AH, Lonner BS, Balderston RA. Segmental contribution toward total cervical range of motion: a comparison of cervical disc arthroplasty and fusion. Spine (Phila Pa 1976). 2011;36(25):E1593-1599.

30. Chang SW, Bohl MA, Kelly BP, Wade C. The segmental distribution of cervical range of motion: a comparison of cervical disc arthroplasty and fusion. Spine (Phila Pa 1976). 2011;36(25):E1593-1599.

31. Brecount H, Goodwin A, Hiltzik DM, Hsu WK. The role of cervical disc arthroplasty in elite athletes. Curr Rev Musculoskelet Med. 2023;16(9):432-437.

32. Sekhon LHS. Two-level artificial disc placement for spondylotic cervical myelopathy. J Clin Neurosci. 2004;11(4):412-415.

22. Doege J, Ayres JM, Mackay MJ, et al. Defining return to sport: a systematic review. Orthop J Sports Med. 2021;9(7):23259671211009589.

33. Schluessmann E, Aghayev E, Staub L, et al. SWISSspine: the case of a governmentally required HTA-registry for total disc arthroplasty: results of cervical disc prostheses. Spine (Phila Pa 1976). 2010;35(24):E1397-1405.

23. Mai HT, Chun DS, Schneider AD, Hecht AC, Maroon JC, Hsu WK. The difference in clinical outcomes after anterior cervical fusion, disk replacement, and foraminotomy in professional athletes.

Clin Spine Surg. 2018;31(1):E80-E84.

34. Huppert J, Beaurain J, Steib JP, et al. Comparison between singleand multi-level patients: clinical and radiological outcomes 2 years after cervical disc replacement. Eur Spine J. 2011;20(9):1417-1426.

24. Reinke A, Behr M, Preuss A, Villard J, Meyer B, Ringel F. Return to sports after cervical total disc replacement.

World Neurosurg. 2017;97:241-246.

35. Zarkadis NJ, Cleveland AW, Kusnezov NA, et al. Outcomes following multilevel cervical disc arthroplasty in the young active population. Mil Med. 2017;182(3):e1790-e1794.

25. Reiter CR, Nelson CT, Satalich JR, et al. Return to sport and active military duty after cervical disc arthroplasty: A systematic review. J Orthop. 2023;39:75-82.

36. Cody JP, Kang DG, Tracey RW, et al Outcomes following cervical disc arthroplasty: a retrospective review. J Clin Neurosci. 2014;21(11):1901-1904.

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From the Texas Back Institute in Plano, Texas.

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A Comparative Review of Lumbar Bone Density Measurement Techniques and Additional Applications The evaluation of vertebral bone density prior to spinal instrumentation is a critical component of the preoperative assessment. Instrumentation of osteoporotic bone can result in complications such as pedicle screw pullout, device subsidence, or device migration.1-5 A growing area of research focuses on screening lumbar bone prior to spinal surgery and may yield great benefits to patients in reducing instrumentation complications.

Dual-energy x-ray absorptiometry (DEXA) has been the gold standard for assessing lumbar bone densit y and classifies bone as either normal, osteopenic, or osteoporotic.6,7 In light of potential shortcomings in DEXA’s lumbar composite values, alternative imaging for bone density measurements have been investigated, such as computed tomography (CT) Hounsfield units (HU), quantitative computed tomog raphy (QCT), and mag net ic resonance imaging (MRI) vertebral bone quality (VBQ). 8,9 In a prev ious issue of Vertebral Columns,10 we explained how to acquire and inter pret t hese lumbar bone density measurements. In the

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present article, we discuss the literature comparing lumbar bone density measurement techniques and present additional applications of these measurements for spinal surger y.

A considerable number of studies have provided evidence that indicate promising alternatives to DEX A for measuring lumbar bone quality.

CT HU and QCT Lumbar Measurements Multiple studies have tested CT HU as a measure of bone density in comparison to DEXA bone mineral density (BMD) values. Viswanathan et al reported a significant correlation between CT HU and DEXA T-scores at the upper lumbar levels (L1-L3) in patients who underwent 1-2 level lumbar fusions.11 The opportunistic availability of CT measurements may provide reasonable identification of osteoporosis, but not all studies agree. Kohan et al found a low to moderate correlation between CT HU measurements and femoral neck DEX A BMD values in patients with adult spinal deformities.12,13 In addition, the cutoffs for defining osteoporotic versus osteopenic or normal

Emily C. Courtois, MS

Mary P. Rogers-LaVanne, PhD

Peter B. Derman, MD, MBA

Alexander M. Satin, MD

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bone are still debated, with normal bone around 160 and 179 HU and osteoporotic/ osteopenic bone closer to 100 and 110 HU.14-16 Other studies have researched correlations between CT HU measurements and incidences of postoperative complications. Murata et al experimented with CT measurements and the incidence of vertebral fractures in an elderly population. They found that CT HU measurements of the anterior one-third of the vertebral body can predict the occurrence of postoperative vertebral fractures.17 Li et al calculated CT HU measurements for the planned screw position on preoperative CT and found these measures to better predict screw loosening than any other vertebral CT HU measurement. They concluded that using specific CT measures of bone density will reduce the risk of screw loosening and their complications in future patients.18 Zaidi et al found that CT HU, when compared to DEXA BMD values, correlated with successful lumbar interbody fusion, cage subsidence, adjacent segment fractures, and pedicle screw loosening.16 As a result, CT HU could be a promising measure of bone density.

St. Jeor et al conducted research regarding CT HU to propose a more comprehensive “expanded spine” criteria to ref ine t he classification of spine surgery patients with potentially low bone density.19 The expanded spine criteria diagnosed osteoporosis on the basis of a CT HU score less than 110 and/or the National Bone Health Alliance (NBHA) guidelines and/or degraded DEXA trabecular bone scores with osteopenic T-score.

Retrospectively applying the expanded spine

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criteria to lumbar spine surgery patients, the authors found that 70.4% of patients with normal or osteopenia DEX A BMD scores were reclassified with osteoporosis. The expanded spine criteria may be especially useful for patients of older age, as men and women older than 70 years were more frequently classified with osteoporosis based on the CT HU criteria than via DEXA or NBHA. Quantitative computed tomography (QCT) is a specialized CT scan that transforms the CT signal in HU based on a calibration phantom using an analytical software.20 Due to the ability of the QCT to separate cortical from trabecular bone, which is a known shortcoming of DEXA, some physicians have ordered QCT to assess bone quality. 21 Lin et al used a QCT-derived volumetric BMD to compare against DEXA T-score values in an older population, finding that QCT was more helpful than DEXA for detecting osteoporosis and predicting vertebral fractures. 22

MRI VBQ Lumbar Measurements A number of studies have tested MRI VBQ as a measure of lumbar bone density. Ehresman et al found that MRI VBQ is an important piece of information in order to assess risk for instrumentation failure. 23 Similarly, Roch et al found that VBQ is significantly correlated with CT bone qualit y values, although they used a different equation for VBQ measurements. 24 Cutoffs for MRI VBQ are also still debated, but lower scores indicate normal bone (<2.41) and greater scores indicate osteoporotic/osteopenic bone quality (>3.0). 25,26 Kadri et al identified a VBQ threshold

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above wh ich pat ient s shou ld u ndergo screening for osteoporosis, 25 and Hu et al reported an association between VBQ and cage subsidence after transforaminal lumbar interbody fusion. 27 Kale et al found a moderate correlation between their measure of VBQ and DEXA, which is consistent with some previously established literature. 28,29 They concluded that this MRI measure has the potential to be a predictor of decreased bone densit y, specifically pertaining to higher VBQ values.

In a recent study, Courtois et al compared lumbar MRI VBQ and CT HU scores to DEXA BMD scores and found that MRI VBQ scores had a much weaker correlation with DEXA than CT HU composites scores.14,30 This study also used receiver operating characteristic area under the curve analyses to discern that CT HU demonstrated a greater ability to differentiate patients between normal and osteopenic/osteoporotic bone than MRI VBQ. Thus, CT HU may be a more reliable measure for lumbar bone mineral density compared to MRI.

subsidence and determined that endplate measurements were a better predictor of subsidence than trabecular bone density measurements af ter standalone lateral lumbar interbody f usions. 31 Jones et al found this to be congruent with their study, noting that significantly elevated endplate measurements using MRI was predictive of severe cage subsidence after the same lumbar procedure. 3

Additional Applications: Lumbar Periendplate or Pedicle Measurements Additional applications using CT HU, QCT, and MRI VBQ have recently been proposed such as at the lumbar endplate or the anticipated pedicle screw trajectory. These other methods may be used to help evaluate complication risks.

Table 1. Abbreviations of terms related to bone density imaging

Cage Subsidence Using QCT, Okano et al measured lumbar endplate bone density to assess the risk of

Qualitative computed tomography

QCT

Signal intensity

SI

Vertebral bone quality

VBQ

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Pedicle Screw Loosening/Pullout Numerous studies have linked low HU values from CT pedicle screw bone density measurements with increased levels of pedicle screw loosening or pullout.18,32-34 These studies confirmed that low bone density predisposes patients to pedicle screw pullout and also showed that this method of measuring bone density using alternative imaging techniques may aid in additional screening prior to lumbar instrumentation.

Ishikawa et al described a met hod of measuring S1 pedicle screw trajectory bone

Term

Abbreviation

Bone mineral density

BMD

Computed tomography

CT

Dual-energy x-ray absorptiometry

DEXA

Hounsfield units

HU

Magnetic resonance imaging

MRI

Picture Archiving and Communication PACS System

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density on CT and its ability to predict screw loosening six months postoperatively.35 This method defined the HU region of interest (ROI) as a rectangular box where the screw was to be placed intraoperatively, and the authors concluded that lower CT HU correlated with screw loosening, suggesting that pedicle screws be placed in an area of the bone with high HU values. Another study examining the S1 pedicle screw trajectory

bone density using MRI instead of CT and concluded t hat V BQ scores moderately correlated with DEXA T-scores and could be a beneficial tool to utilize in addition to the DEXA report. 36 In some cases, especially if there is a concern for artificially increased DEXA values, utilizing these other techniques may provide more bone quality information prior to spinal surgery.

References 1. Bertagnoli R, Zigler J, Karg A, Voigt S. Complications and strategies for revision surgery in total disc replacement. Orthop Clin North Am. 2005;36(3):389-395.

2. Ouyang H, Hu Y, Hu W, et al. Incidences, causes and risk factors of unplanned reoperations within 30 days of spine surgery: a single-center study based on 35,246 patients.

Spine J. 2022;22(11):1811-1819.

3. Jones C, Okano I, Arzani A, et al.

The predictive value of a novel site-specific MRI-based bone quality assessment, endplate bone quality (EBQ), for severe cage subsidence among patients undergoing standalone lateral lumbar interbody fusion.

Spine J. 2022;22(11):1875-1883.

4. Soliman MAR, Aguirre AO, Kuo CC, et al.

Vertebral bone quality score independently predicts cage subsidence following transforaminal lumbar interbody fusion. Spine J. 2022;22(12):2017-2023.

5. Sakai Y, Takenaka S, Matsuo Y, et al.

Hounsfield unit of screw trajectory as a predictor of pedicle screw loosening after single level lumbar interbody fusion. J Orthop Sci. 2018;23(5):734-738.

6. Link TM. Osteoporosis imaging: state of the art and advanced imaging. Radiology. 2012;263(1):3-17.

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7. Krugh M, Langaker MD. Dual-Energy X-Ray Absorptiometry. StatPearls Publishing LLC; 2023.

8. Kim AYE, Lyons K, Sarmiento M, Lafage V, Iyer S. MRI-based score for assessment of bone mineral density in operative spine patients.

Spine. 2023;48(2):107-112.

9. Ahmad A, Crawford CH III, Glassman SD, Dimar JR II, Gum JL, Carreon LY. Correlation between bone density measurements on CT or MRI versus DEXA scan: a systematic review. N Am Spine Soc J. 2023;14:100204.

10. Courtois EC, Satin AM, Rogers-LaVanne MP, Derman PB. Lumbar bone density measurements: using CT and MRI scans as alternatives to DEXA. Vertebral Columns. Summer 2023:16-19.

11. Viswanathan VK, Shetty AP, Rai N, Sindhiya N, Subramanian S, Rajasekaran S. What is the role of CT-based Hounsfield unit assessment in the evaluation of bone mineral density in patients undergoing 1- or 2-level lumbar spinal fusion for degenerative spinal pathologies? A prospective study. Spine J. 2023;23(10):1427-1434. doi:10.1016/j.spinee.2023.05.015 12. Kohan EM, Nemani VM, Hershman S, Kang DG, Kelly MP. Lumbar computed tomography scans are not appropriate surrogates for bone mineral density scans in primary adult spinal deformity. Neurosurg Focus. 2017;43(6):E4.

13. Kim KJ, Kim DH, Lee JI, Choi BK, Han IH, Nam KH. Hounsfield units on lumbar computed tomography for predicting regional bone mineral density.

Open Med (Wars). 2019;14:545-551.

14. Courtois EC, Ohnmeiss DD, Guyer RD. Assessing lumbar vertebral bone quality: a methodological evaluation of CT and MRI as alternatives to traditional DEXA. Eur Spine J. 2023;32(9):3176-3182.

15. Yaprak G, Gemici C, Seseogullari OO, Karabag IS, Cini N. CT derived Hounsfield unit: an easy way to determine osteoporosis and radiation related fracture risk in irradiated patients. Front Oncol. 2020;10:742.

16. Zaidi Q, Danisa OA, Cheng W. Measurement techniques and utility of Hounsfield unit values for assessment of bone quality prior to spinal instrumentation: a review of current literature. Spine. 2019;44(4):E239-E244.

17. Murata K, Fujibayashi S, Otsuki B, Shimizu T, Matsuda S. Low Hounsfield unit values at sagittal section on computed tomography predicts vertebral fracture following short spinal fusion. J Orthop Sci. Published online March 21, 2023. doi:10.1016/j.jos.2023.03.008 18. Li J, Zhang Z, Xie T, Song Z, Song Y, Zeng J. The preoperative Hounsfield unit value at the position of the future screw insertion is a better predictor of screw loosening than other methods.

Eur Radiol. 2023;33(3):1526-1536.

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Conclusion Recently, a number of alternative techniques have emerged to measure spine bone densit y in an effort to address the shortcomings of DEXA. Despite a number of studies comparing these methods, there is an overall lack of standardization within spine surgery. Some studies would argue that CT seems more closely correlated than MRI with DEXA BMD, while other studies

29

found VBQ to be an adequate tool for assessing osteoporosis. 8,23,25 Complimenting DEX A with alternative methods for measuring bone density prior to spinal instrumentation surgeries may lead to less hardware-related complications.

The continued development of this field of study will aid spine surgeons in their decision-making process. l

References, continued 19. St Jeor JD, Jackson TJ, Xiong AE, et al. Osteoporosis in spine surgery patients: what is the best way to diagnose osteoporosis in this population? Neurosurg Focus. 2020;49(2):E4.

26. Ehresman J, Schilling A, Yang X, et al. Vertebral bone quality score predicts fragility fractures independently of bone mineral density. Spine J. 2021;21(1):20-27.

32. Xu F, Zou D, Li W, et al. Hounsfield units of the vertebral body and pedicle as predictors of pedicle screw loosening after degenerative lumbar spine surgery. Neurosurg Focus. 2020;49(2):E10.

20. Link TM, Lang TF. Axial QCT: clinical applications and new developments.

J Clin Densitom. 2014;17(4):438-448.

27. Hu YH, Yeh YC, Niu CC, et al. Novel MRI-based vertebral bone quality score as a predictor of cage subsidence following transforaminal lumbar interbody fusion. J Neurosurg Spine. Published online May 13, 2022. doi:10.3171/2022.3.Spine211489

33. Chen Z, Lei F, Ye F, et al. Prediction of pedicle screw loosening using an MRI-based vertebral bone quality score in patients with lumbar degenerative disease. World Neurosurg. 2023;171:e760-e767.

21. Adams JE. Quantitative computed tomography. Eur J Radiol. 2009;71(3):415-424.

22. Lin W, He C, Xie F, et al. Discordance in lumbar bone mineral density measurements by quantitative computed tomography and dual-energy X-ray absorptiometry in postmenopausal women: a prospective comparative study. Spine J. 2023;23(2):295-304.

23. Ehresman J, Ahmed AK, Lubelski D, et al. Vertebral bone quality score and postoperative lumbar lordosis associated with need for reoperation after lumbar fusion. World Neurosurg. 2020;140:e247-e252.

24. Roch PJ, Çelik B, Jäckle K, et al. Combination of vertebral bone quality scores from different magnetic resonance imaging sequences improves prognostic value for the estimation of osteoporosis. Spine J. 2023;23(2):305-311.

25. Kadri A, Binkley N, Hernando D, Anderson PA. Opportunistic use of lumbar magnetic resonance imaging for osteoporosis screening. Osteoporos Int. 2022;33(4):861-869.

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28. Kale H, Yadav S. Can routine MRI spine T1 sequences be used for prediction of decreased bone density?

Acta Radiol. 2023;64(1):164-171.

29. Li W, Tong T, Zhu H, et al. Hounsfield units value is a better predictor of bone mineral density than the vertebral bone quality score of magnetic resonance imaging in patients with lumbar degenerative diseases. Research Square.

Preprint posted online January 3, 2022. doi:10.21203/rs.3.rs-1110968/v1 30. Zou KH, Tuncali K, Silverman SG. Correlation and simple linear regression. Radiology. 2003;227(3):617-22.

31. Okano I, Jones C, Salzmann SN, et al. Endplate volumetric bone mineral density measured by quantitative computed tomography as a novel predictive measure of severe cage subsidence after standalone lateral lumbar fusion.

Eur Spine J. 2020;29(5):1131-1140.

34. Wichmann JL, Booz C, Wesarg S, et al. Quantitative dual-energy CT for phantomless evaluation of cancellous bone mineral density of the vertebral pedicle: correlation with pedicle screw pull-out strength.

Eur Radiol. 2015;25(6):1714-20.

35. Ishikawa Y, Katsumi K, Mizouchi T, Sato M, Yamazaki A. Importance of computed tomography Hounsfield units in predicting S1 screw loosening after lumbosacral fusion.

J Clin Neurosci. 2023;113:1-6.

36. Huang W, Gong Z, Wang H, et al. Use of MRI-based vertebral bone quality score (VBQ) of S1 body in bone mineral density assessment for patients with lumbar degenerative diseases. Eur Spine J. 2023;32(5):1553-1560

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FRACTURE

From The CORE Institute in Phoenix, Arizona.

Update on Vertebral Augmentation for Thoracolumbar Fragility Fractures Thoracolumbar fragility fractures are the most common osteoporotic fracture worldwide and are thought to occur in 30% to 50% of individuals older than 50 years.1 While many osteoporotic vertebral fractures are asymptomatic, Brandon P. Hirsch, MD they have the potential to cause significant pain and functional disability in cases of delayed healing or nonunion. Historically, nonsurgical treatment has been the mainstay of care for stable-appearing thoracolumbar vertebral fractures; however there is a paucity of evidence supporting its effectiveness.2,3 Vertebral augmentation, also known as vertebroplasty or kyphoplasty, involves injecting polymethylmethacrylate cement into fractured vertebrae via a percutaneous approach. While the efficacy of the procedure was disputed following its development in the 1990s, a robust body of literature now supports its ability to reduce pain and improve function in patients with osteoporotic vertebral fractures.2,4–8 Nonsurgical treatment has historically been the mainstay of the initial treatment of osteoporotic vertebral fractures and often includes analgesics, activity modification and bracing. Despite their widespread use, evidence supporting the effectiveness of orthoses in

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improving outcomes after vertebral fractures is lacking.9 A 2009 randomized prospective study of treatment with thoracolumbosacral orthoses (TLSO) by Bailey et al demonstrated no significant differences in pain scores or functional outcomes when compared with unbraced patients.10 Similar findings were described by Kim et al in a 2014 prospective study comparing rigid versus soft orthoses versus no bracing for osteoporotic vertebral fractures. No differences in pain reduction were demonstrated in patients treated with bracing versus those who were not.11 While the majority of patients with symptomatic vertebral compression fractures go on to heal regardless of treatment modality, approximately 10% to 20% of patients fail to improve without procedural intervention.3,12 Several authors have studied risk factors for treatment failure with conservative management.13 Age, presence of middle column injury, hyperintensity on T2-weighted imaging, and location within the thoracolumbar junction have all been cited as risk factors for nonunion and persistent pain.14,15 The use of opioids for treatment of fracture-related pain is of concern due to the potential for dependence as well their side effect profile (ie, constipation, nausea, delirium). The side effects of opioid use are

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particularly problematic in patients with osteoporotic fractures given their advanced age and frailty. Multiple studies have demonstrated a significant reduction or elimination of opioid use in patients undergoing vertebral augmentation for osteoporotic thoracolumbar fractures.16–18 The largest of these studies utilized the MarketScan database to analyze opioid prescription data in 8,845 patients.17 In this population, approximately 75% of patients were using opioids before the procedure. Within this group, 49% of patients discontinued opioid use following vertebral augmentation while an additional 8.5% of the cohort reduced their opioid intake. Data on opioid use in patients treated nonsurgically were not included in the study.

Like other fragility fractures, osteoporotic vertebral fractures are associated with increased mortality risk.19–21 A recent study analyzed 492 cases of patients older than 65 years with vertebral compression fractures, finding an overall mortality rate of 13.4% at 1 year and 40.6% at 5 years.20 Although some authors have reported conflicting results, patients undergoing vertebral augmentation seem to have lower mortality when compared with patients treated nonoperatively.18,22–24 A 2015 cohort analysis of more than 1.2 million cases of vertebral fracture within the national Medicare claims database demonstrated that patients undergoing kyphoplasty had 55% mortality risk reduction when compared to patients treated nonoperatively.22 Hinde et al performed a meta-analysis of 16 studies that included more than 2 million patients with osteoporotic vertebral fractures. The authors found a 22% mortality risk reduction at up

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to 10 years in patients undergoing vertebral augmentation.23 Restoration and maintenance of vertebral body height after vertebral augmentation with polymethylmethacrylate remains a challenge.

In most clinical settings, patients undergo vertebral augmentation weeks to months after their fracture has occurred, by which time initial fibrous healing has taken place. Fracture reduction via traditional balloon kyphoplasty is limited by the risk of balloon rupture as well as the need to remove the balloon prior to cement delivery. To address this problem, “third generation” vertebral augmentation techniques have been developed that involve placing permanent structural implants within the fractured vertebrae via a transpedicular approach.25 Currently available implants are composed of either titanium or polyetheretherketone. In certain systems, these implants are secured by injecting polymethylmethacrylate cement after expansion, whereas in other systems the implants are self-stabilizing. In a recent meta-analysis that pooled results from 1320 treated fractures, third-generation systems provided superior restoration of vertebral height and reduction of kyphosis with equivalent improvement in pain scores and functional outcomes when compared with traditional techniques for vertebral augmentation. 26 Long-term studies are needed to determine whether this improved restoration of sagittal alignment confers superior clinical benefit.

Osteoporotic vertebral fractures are a common diagnosis treated by spine surgeons worldwide. While many of these fractures will heal uneventfully, certain patients experience severe ongoing pain related to delayed healing,

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nonunion, and/or sagittal deformity. Modern studies of vertebral augmentation support its use as a safe and effective treatment option for this growing patient population. Vertebral

augmentation technology continues to evolve with a focus on improving sagittal realignment capability in order to deliver superior long-term clinical outcomes. l

References 1. Ballane G, Cauley JA, Luckey MM, Fuleihan FE. Worldwide prevalence and incidence of osteoporotic vertebral fractures.

Osteoporos Int. 2017;28(5):1531-1542.

2. Rzewuska M, Ferreira M, Mclachlan AJ, et al. The efficacy of conservative treatment of osteoporotic compression fractures on acute pain relief: a systematic review with meta-analysis.

Eur Spine J. 2015;24(4):702-714.

orthosis and no orthosis for the treatment of thoracolumbar burst fractures: interim analysis of a multicenter randomized clinical equivalence trial. J Neurosurg Spine. 2009;11(3):295–303.

Spine (Phila Pa 1976). 2011;36:E1266-E1269.

19. Bliuc D, Nguyen ND, Milch VE, Nguyen TV, Eisman JA, Center JR. Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. JAMA. 2009;301:513–521.

11. Kim H-J, Yi J-M, Cho H-G, et al. Comparative study of the treatment outcomes of 20. Gutiérrez-González R, Royuela A, Zamarron osteoporotic compression fractures without A. Survival following vertebral compression neurologic injury using a rigid brace, a fractures in population over 65 years old. soft brace, and no brace: a prospective Aging Clin Exp Res. 2023;35:1609–1617. randomized controlled non-inferiority trial.

3. Petitt JC, Desai A, Kashkoush A, et 21.

Gold LS, Suri P, O’Reilly MK, Kallmes DF, J Bone Joint Surg Am. 2014;96:1959–1966. al. Failure of conservatively manHeagerty PJ, Jarvik JG. Mortality among 12. Soultanis K, Thano A, Soucacos PN. aged traumatic vertebral compresolder adults with osteoporotic vertebral fracOutcome of thoracolumbar compression fractures: a systematic review. ture. Osteoporos Int. 2023;34:1561–1575. sion fractures following non-operative World Neurosurg. 2022;165:81–8.

22. Edidin AA, Ong KL, Lau E, Kurtz SM. treatment. Injury. 2021;52:3685–3690.

4. Pron G, Hwang M, Smith R, et al. Cost-effecMorbidity and mortality after vertetiveness studies of vertebral augmentation 13. Muratore M, Ferrera A, Masse A, Bistolbral fractures: comparison of vertebral fi A. Osteoporotic vertebral fractures: for osteoporotic vertebral fractures: a sysaugmentation and nonoperative managepredictive factors for conservative tematic review. Spine J. 2022;22:1356–1371. ment in the medicare population. Spine treatment failure. A systematic review.

(Phila Pa 1976). 2015;40:1228–1241.

5. Beall DP, Phillips TR. Vertebral augEur Spine J. 2018;27:2565–2576. mentation: an overview. Skeletal 23. Hinde K, Maingard J, Hirsch JA, Phan K, 14. Tsujio T, Nakamura H, Terai H, et al. CharacRadiol. 2023;52:1911–1920.

Asadi H, Chandra RV. Mortality outcomes teristic radiographic or magnetic resonance of vertebral augmentation (vertebroplasty 6. Hoffmann J, Preston G, Whaley J, Khalil JG. images of fresh osteoporotic vertebral and/or balloon kyphoplasty) for osteoVertebral augmentation in spine surgery. J fractures predicting potential risk for porotic vertebral compression fractures: Am Acad Orthop Surg. 2023;31:477–489. nonunion: a prospective multicenter study. a systematic review and meta-analy7. Klazen CAH, Lohle PNM, de Vries J, Spine (Phila Pa 1976). 2011;36:1229–1235. sis. Radiology. 2020;295:96–103. et al. Vertebroplasty versus conser15. Inose H, Kato T, Ichimura S, et al. Risk 24. Cazzato RL, Bellone T, Scardapane vative treatment in acute osteoporotfactors of nonunion after acute osteoM, et al. Vertebral augmentation reic vertebral compression fractures porotic vertebral fractures: a prospecduces the 12-month mortality and (Vertos II): an open-label randomised tive multicenter cohort study. Spine morbidity in patients with osteoporottrial. Lancet. 2010;376:1085–1092.

(Phila Pa 1976). 2020;45:895–902. ic vertebral compression fractures.

8. Clark W, Bird P, Gonski P, et al. SafeEur Radiol. 2021;31:8246–8255.

16. Tolba R, Bolash RB, Shroll J, et al. Kyphty and efficacy of vertebroplasty for oplasty increases vertebral height, 25. Manz D, Georgy M, Beall DP, Baroud G, Georacute painful osteoporotic fractures decreases both pain score and opiate gy BA, Muto M. Vertebral augmentation with (VAPOUR): a multicentre, randomised, requirements while improving functional spinal implants: third-generation vertebrodouble-blind, placebo-controlled tristatus. Pain Pract. 2014;14:E91-E97. plasty. Neuroradiology. 2020;62:1607–1615. al. Lancet. 2016;388:1408–1416.

17. Ni W, Ricker C, Quinn M, et al. Trends in 26. Dong C, Zhu Y, Zhou J, et al. Ther9. Rzewuska M, Ferreira M, McLachlan AJ, opioid use following balloon kyphoplasapeutic efficacy of third-generation Machado GC, Maher CG. The efficacy of ty or vertebroplasty for the treatment percutaneous vertebral augmentation conservative treatment of osteoporotic of vertebral compression fractures. system (PVAS) in osteoporotic vertecompression fractures on acute pain Osteoporos Int. 2022;33:821–837. bral compression fractures (OVCFs): a relief: a systematic review with meta-analsystematic review and meta-analysis.

18. Gerling MC, Eubanks JD, Patel R, Whang PG, ysis. Eur Spine J. 2015;24(4):702–714.

Biomed Res Int. 2022;2022:9637831.

Bohlman HH, Ahn NU. Cement augmentation 10. Bailey CS, Dvorak MF, Thomas KC, et of refractory osteoporotic vertebral comal. Comparison of thoracolumbosacral pression fractures: survivorship analysis.

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From Midwest Orthopaedic at Rush, Rush University Medical Center, in Chicago, Illinois.

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An Update on Multimodal Analgesia Are We Better at Managing Postoperative Pain?

Since its introduction in 1993, multimodal analgesia (MMA) has been used to provide a synergistic analgesic effect, therefore reducing the adverse effects of any individual drug used in isolation at higher doses.1 The use of MMA has subsequently been incorporated into the concept of Enhanced Recovery After Surgery (ERAS) and is used alongside preoperative patient education/ optimization, preemptive analgesia, standardized intraoperative anesthesia, early mobilization, and novel medication classes in order to enhance pain control and minimize the use of opioid analgesics.2 In hopes of mitigating the unwanted side effects of narcotics, MMA and ERAS protocols have been widely adapted across surgical subspecialties. 3-4 Given these successes, spine surgery centers have begun to adopt similar protocols in order to enhance patient outcomes and satisfaction. 5 With increasingly widespread implementation of MMA and ERAS protocols, a critical review of their implementation and outcomes is necessary.

Efficacy of MMA/ERAS protocols Multiple systematic reviews of spine operative MMA/ERAS protocols have shown that their use results in significant reduction in the length of hospital stay and reduced postoperative pain scores.6–9 Equally important, these reviews have found that the ER AS

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protocols are associated with a decreased rate of perioperative complications.6,8 ER AS protocols have shown meaningful reductions in narcotics usage following spine surWilliam Conaway, MD gery.10-12 In a prospective study, Flanders et al found their ERAS protocol patients took significantly fewer opioid medications after elective spine surgery at 1, 3, and 6 months postoperatively.

At the 6 month assessment, 52% of the traditional pain manageArash Sayari, MD ment group reported continued use as opposed to 24% in the ER AS protocol group.11 In a randomized trial of 284 patients, the ERAS group utilized significantly less intravenous opioid and patient-controlled analgesia than the standard-of-care group.13 At 6-month follow-up, significantly fewer ERAS participants reported any opioid use (11.4% vs 20.6%).

Additionally, mean VAS scores were lower (3.0 vs 4.0), Foley catheters were used less often, and patients were discharged home more often (91.1% vs 81.0%) in the ER AS group.13 This trend has continued in various spine surgical procedures, including anterior cervical discectomy and fusion, cervical disc replacement, lumbar laminectomy, lumbar fusion, and transforaminal interbody

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in comparison to an equivalent intravenous morphine dosage. 28

fusion.14–20 Similar results were found in a systematic review relating to the use of ERAS in pediatric patients undergoing deformity correction with decreased postoperative pain scores and length of stay.21 In addition to the clinical benefits, MMA/ ERAS protocols have been noted as effective cost saving measures across several types of spine surgery, even despite their upfront costs of implementation. 22,23

Protocol Update Preoperative Adequate education and counseling has been shown to reduce postoperative VAS scores and LOS after spine surgery. 24 Preoperative analgesia protocols vary but are generally aimed at mitigating the effects of imminent painful stimuli. Preoperative administration of 600–1200 mg gabapentin or 100–150 mg pregabalin has been shown to reduce postoperative pain and narcotic consumption.25-27 Utilization of a combination of pregabalin, acetaminophen, celecoxib, and extended release oxycodone has also demonstrated reduced postoperative pain

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Intraoperative Pain produced during spinal surger y is localized to the operative field; therefore, regional and local anesthetic administration is an attractive option. Erector spinae (ESP) blocks, thoracolumbar interfascial plane blocks (TLIP), and quadratus lumborum blocks have all been described. In a cohort of single level lumbar fusion patients, ESP blocks were found to result in lower immediate postoperative VAS pain scores, less postoperative opioid consumption, and higher patient satisfaction.29 Similarly, TLIP blocks were found in a meta-analysis to lower first postoperative day pain scores and overall use of patient-controlled analgesia. 30 Local infiltration of the wound and incisional site is also frequently used to decrease postoperative pain. Administration of lidocaine with epinephrine into the incisional area followed by wound closure with 30-40 mL of 0.5% ropivacaine has been found to decrease postoperative pain and opioid consumption.31 The addition of alpha-2 agonists, including clonidine or dexmedetomidine, to these anesthetics has been found to enhance their duration and effectiveness.32 Finally, end-ofcase epidural analgesia has demonstrated decreases in postoperative pain and opioid consumption. 33 Adjunctive ketamine has been used in pain management since the discovery of the N-methyl-D-aspartate (NMDA) receptor’s role in opioid-induced hyperalgesia. 34 A recent systematic review and meta-analysis of

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30 randomized controlled trials found that perioperative low dose ketamine resulted in lower visual analog scale pain scores and opioid requirements in the immediate postoperative period while also decreasing the incidence of nausea and vomiting in this period. 35 Similarly, magnesium has been found to act on the NMDA receptor, and intraoperative administration was found to reduce immediate postoperative opioid consumption. 36 Intraoperative dexamethasone is commonly used to decrease postoperative nausea, and one study found that a dose of at least 0.11-0.2 mg/kg intraoperatively decreased postoperative opioid requirements in lumbar spine surgery patients without increasing the incidence of wound issues. 37

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Postoperative Adequate postoperative pain control is integral in improving functional outcomes, facilitating early mobilization, and preventing the development of chronic pain.38 From a medication standpoint, acetaminophen, nonsteroidal anti-inflammatory drugs (or selective COX-2 inhibitors), muscle relaxers, and gabapentinoids remain the mainstays of opioid-limiting treatment.39 In addition to medical treatments, early mobilization remains a pillar of postoperative care. Multiple studies have shown that early mobilization reduces length of stay and morbidity.40 Literature review reveals a multitude of different specific MMA protocols used by surgeons, and the best practice remains a topic of ongoing research. l

References analgesia in spine surgery. J Am Acad Orthop Surg. 2017;25(4):260-268.

for spine surgery: a systematic review.

World Neurosurg. 2019;130:415-426.

2. Bullock WM, Kumar AH, Manning E, Jones J. Perioperative analgesia in spine surgery: a review of current data supporting future direction. Orthop Clin North Am. 2023;54(4):495-506.

6. Pennington Z, Cottrill E, Lubelski D, Ehresman J, Theodore N, Sciubba DM. Systematic review and meta-analysis of the clinical utility of Enhanced Recovery After Surgery pathways in adult spine surgery. J Neurosurg Spine. 2021;34(2):325-347.

10. Uhrbrand P, Helmig P, Haroutounian S, Vistisen ST, Nikolajsen L. Persistent opioid use after spine surgery: a prospective cohort study. Spine (Phila Pa 1976). 2021;46(20):1428-1435.

3. Wheeler M, Oderda GM, Ashburn MA, Lipman AG. Adverse events associated with postoperative opioid analgesia: a systematic review. J Pain. 2002;3(3):159-180.

7. Tong Y, Fernandez L, Bendo JA, Spivak JM. Enhanced Recovery After Surgery trends in adult spine surgery: a systematic review. Int J Spine Surg. 2020;14(4):623-640.

4. Berger RA, Sanders SA, Thill ES, Sporer SM, Della Valle C. Newer anesthesia and rehabilitation protocols enable outpatient hip replacement in selected patients. Clin Orthop Relat Res. 2009;467(6):1424-1430.

8. Zaed I, Bossi B, Ganau M, Tinterri B, Giordano M, Chibbaro S. Current state of benefits of Enhanced Recovery After Surgery (ERAS) in spinal surgeries: a systematic review of the literature.

Neurochirurgie. 2022;68(1):61-68.

12. Chang HK, Huang M, Wu JC, Huang WC, Wang MY. Less opioid consumption with Enhanced Recovery After Surgery transforaminal lumbar interbody fusion (TLIF): a comparison to standard minimally-invasive TLIF. Neurospine. 2020;17(1):228-236.

5. Kurd MF, Kreitz T, Schroeder G, Vaccaro AR. The role of multimodal

9. Dietz N, Sharma M, Adams S, et al. Enhanced Recovery After Surgery (ERAS)

13. Ali ZS, Albayar A, Nguyen J, et al.

A randomized controlled trial to

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

Anesth Analg. 1993;77(5):1048-1056.

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11. Flanders TM, Ifrach J, Sinha S, et al.

Reduction of postoperative opioid use after elective spine and peripheral nerve surgery using an Enhanced Recovery After Surgery program. Pain Med (United States). 2020;21(12):3283-3291.

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References, continued assess the impact of Enhanced Recovery After Surgery on patients undergoing elective spine surgery.

Ann Surg. 2023;278(3):408-416.

14. Bohl DD, Louie PK, Shah N, et al.

Multimodal versus patient-controlled analgesia after an anterior cervical decompression and fusion. Spine (Phila Pa 1976). 2016;41(12):994-998.

15. Singh K, Bohl DD, Ahn J, et al. Multimodal analgesia versus intravenous patient-controlled analgesia for minimally invasive transforaminal lumbar interbody fusion procedures. Spine (Phila Pa 1976). 2017;42(15):1145-1150.

16. Parrish 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.

17. Nolte 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.

18. Prabhu MC, Jacob KC, Patel MR, Nie JW, Hartman TJ, Singh K. Multimodal analgesic protocol for cervical disc replacement in the ambulatory setting: clinical case series.

J Clin Orthop Trauma. 2022;35.

program: a single-center, retrospective cohort study. J Neurosurg Anesthesiol. 2023;35(2):187-193.

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

Clin Neurosurg. 2018;83(4):827-834.

24. Burgess LC, Arundel J, Wainwright TW. The effect of preoperative education on psychological, clinical and economic outcomes in elective spinal surgery: a systematic review. Healthc. 2019;7(1).

25. Pandey CK, Navkar DV, Giri PJ, et al.

Evaluation of the optimal preemptive dose of gabapentin for postoperative pain relief after lumbar diskectomy: a randomized, double-blind, placebo-controlled study. J Neurosurg Anesthesiol. 2005;17(2):65-68.

26. Khan ZH, Rahimi M, Makarem J, Khan RH. Optimal dose of pre-incision/ post-incision gabapentin for pain relief following lumbar laminectomy: a randomized study. Acta Anaesthesiol Scand. 2011;55(3):306-312.

27. Rivkin A, Rivkin MA. Perioperative nonopioid agents for pain control in spinal surgery. Am J Heal Pharm. 2014;71(21):1845-1857.

19. Wang P, Wang Q, Kong C, et al.

Enhanced Recovery After Surgery (ERAS) program for elderly patients with short-level lumbar fusion. J Orthop Surg Res. 2020;15(1).

28. Spreng UJ, Dahl V, Rãder J. Effect of a single dose of pregabalin on post-operative pain and pre-operative anxiety in patients undergoing discectomy. Acta Anaesthesiol Scand. 2011;55(5):571-576.

20. Ifrach J, Basu R, Joshi DS, et al.

Efficacy of an Enhanced Recovery After Surgery (ERAS) pathway in elderly patients undergoing spine and peripheral nerve surgery. Clin Neurol Neurosurg. 2020;197.

29. Goel VK, Chandramohan M, Murugan C, et al. Clinical efficacy of ultrasound guided bilateral erector spinae block for single-level lumbar fusion surgery: a prospective, randomized, case-control study. Spine J. 2021;21(11):1873-1880.

21. Pennington Z, Cottrill E, Lubelski D, et al. Clinical utility of Enhanced Recovery After Surgery pathways in pediatric spinal deformity surgery: systematic review of the literature. J Neurosurg Pediatr. 2021;27(2):225-238.

30. Long G, Liu C, Liang T, Zhan X. The efficacy of thoracolumbar interfascial plane block for lumbar spinal surgeries: a systematic review and meta-analysis.

J Orthop Surg Res. 2023;18(1):318.

22. Naik BI, Dunn LK, Wanchek TN. Incremental cost-effectiveness analysis on length of stay of an enhanced recovery after spine surgery

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31. Bianconi M, Ferraro L, Traina GC, et al. Pharmacokinetics and efficacy of ropivacaine continuous wound instillation after joint replacement surgery.

Br J Anaesth. 2003;91(6):830-835.

32. Li J, Yang JS, Dong BH, Ye JM. The effect of dexmedetomidine added to preemptive ropivacaine infiltration on postoperative pain after lumbar fusion surgery: a randomized controlled trial. Spine (Phila Pa 1976). 2019;44(19):1333-1338.

33. Soffin EM, Wetmore DS, Beckman JD, et al. Opioid-free anesthesia within an Enhanced Recovery After Surgery pathway for minimally invasive lumbar spine surgery: a retrospective matched cohort study. Neurosurg Focus. 2019;46(4).

34. Mion G, Villevieille T. Ketamine pharmacology: an update (pharmacodynamics and molecular aspects, recent findings).

CNS Neurosci Ther. 2013;19(6):370-380.

35. Zhou L, Yang H, Hai Y, Cheng Y. Perioperative low-dose ketamine for postoperative pain management in spine surgery: a systematic review and meta-analysis of randomized controlled trials. Pain Res Manag. 2022;2022:1507097.

36. Yue L, Lin ZM, Mu GZ, Sun HL. Impact of intraoperative intravenous magnesium on spine surgery: a systematic review and meta-analysis of randomized controlled trials. eClinicalMedicine. 2022;43:101246.

37. Wittayapairoj A, Wittayapairoj K, Kulawong A, Huntula Y. Effect of intermediate dose dexamethasone on post-operative pain in lumbar spine surgery: a randomized, triple-blind, placebo-controlled trial. Asian J Anesthesiol. 2017;55(3):73-77.

38. Bajwa SJS, Haldar R. Pain management following spinal surgeries: an appraisal of the available options. J Craniovertebr Junction Spine. 2015;6(3):105-110.

39. Walker CT, Gullotti DM, Prendergast V, et al. Implementation of a standardized multimodal postoperative analgesia protocol improves pain control, reduces opioid consumption, and shortens length of hospital stay after posterior lumbar spinal fusion.

Neurosurgery. 2020;87(1):130-136.

40. Burgess LC, Wainwright TW. What is the evidence for early mobilisation in elective spine surgery? A narrative review. Healthc. 2019;7(3):92.

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From Midwest Orthopaedic at Rush, Rush University Medical Center, in Chicago, Illinois.

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Intradiscal Injections Is There Evidence to Support It? Intervertebral disc degeneration is one of the most common causes of chronic low back pain in adults. Compared to other sources of chronic low back pain, such as the sacroiliac joint or posterior facets, discogenic pain is more common in younger patients.1 The pathomechanisms underlying discogenic back pain are incompletely understood, but they are thought to involve a complex interplay between inflammation, hypermobility, and nerve ingrowth and upregulation, all of which may be further modulated by psychosocial factors such as depression or the presence of work-related injury.2 In the midst of such complexity, identifying a low-cost, minimally invasive treatment strategy such as intradiscal injection for the treatment of discogenic back pain would be of great clinical utility, but does the evidence support it?

Intradiscal Biologics Among the different types of intradiscal injections, intradiscal biologics are currently perhaps the most popular. A 2022 systematic review examined several intradiscal biologic agents for the treatment of discogenic low back pain, including platelet rich plasma (PRP), autologous bone marrow aspirate concentrate (BMAC), autologous mesenchymal stroma cells (MSCs), and allograft disc chondrocytes.3 Among the 2 randomized controlled trials and 10 observational cohort studies included in the review,4-14 the aggregate rate of success (defined as pain

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reduction of ≥50% from baseline) George W. Fryhofer, for PRP and MSC injections at 6 MD, MSc months were 54.8% and 53.5%, respectively. However, the review ultimately concluded that the body of evidence supporting intradiscal MSCs and PRP was limited only to observational data that was “very low quality” for a variety of reasons, Gregory Lopez, MD ranging from low sample size to insufficient blinding. Additionally, success rates in these studies often had lower end confidence intervals that overlapped with clinically important thresholds, suggesting the absence of clinical significance. Finally, the one randomized controlled trial that was included for PRP injection alone—comparing PRP versus sham 8 weeks after injection13—was also found to be “very low quality,” given the high risk of bias arising from inadequate randomization and missing outcome data in more than 20% of patients in that study.

Other reviews have also been performed, including one that focused solely on injection of BMAC and culture-expanded bone marrow MSCs.15 In that review, 16 studies were identified, and it was generally concluded that intradiscal autologous or allogeneic BMAC and culture-expanded bone marrow-derived MSCs did improve pain compared to baseline.

However, the quality of evidence among those studies was also found to be “very low” due to heterogeneity and limited generalizability.

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Patient selection has also been studied. In a retrospective analysis of patients receiving intradiscal PRP injection with discogenic low back pain, Akeda et al found that patients who had more than 1 disc injected and patients with posteriorly located high intensity zones on magnetic resonance imaging (MRI) had relatively worse outcomes 12 months after the injection, as measured by changes in visual analog score and Oswestry Disability Index, respectively.16 This study supports the notion that the presence of posterior high intensity zones on MRI and having multiple “target” discs may serve as negative prognostic indicators for patients undergoing PRP injection.

Nonbiologic Agents Despite the current popularity of biologics, other agents historically have also been trialed as the key component in intradiscal injection formulations for the treatment of discogenic back pain.

One of the oldest among these are chemonucleolytic enzymes, first described by Dr. Lyman Smith in 1963, wherein intradiscal injection of the enzyme chymopapain caused dissolution of the nucleus pulposus having been first trialed in dogs and then humans.17 Since then, the treatment was studied for many years but without resounding success, up until 2002 when commercial production of chymopapain was stopped due to reports of serious adverse events, including anaphylaxis and neurologic complications. However, over the past 2 decades, there has been renewed interest in a more specific and potentially less inflammatory chemonucleolytic enzyme: proteus vulgaris chondroitin sulfate ABC endolyase (condoliase). This enzyme,

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which is more specific to targeting the nucleus pulposus, is currently being studied as a new treatment option for discogenic back pain and has been approved by the drug regulatory authority in Japan following successful clinical phase II and phase III trials.18,19 Methylene blue—a substance that has been postulated to block nerve conduction and possess an anti-inflammatory effect20,21—has also been used for the treatment of discogenic back pain and was recently studied in a 2018 meta-analysis of 5 studies utilizing intradiscal injection. That review found a significant improvement in visual analog scores at 3 months after injection while also recognizing the need for larger sample sizes and better randomized controlled trials.22 Corticosteroids have also been widely used in orthopedics as a treatment to quell inflammation—even if temporarily—and the intervertebral disc is no exception. Cao et al performed a randomized controlled trial of intradiscal injection of corticosteroid versus saline among 120 patients with discogenic low back pain and end plate Modic changes who had undergone discography but did not wish to undergo surgery.23 That study found a significant improvement in visual analog scale and Oswestry function scores at 3 and 6 months following corticosteroid injection compared to saline control. More recently, a systematic review including 8 studies of patients with chronic discogenic pain found a significant improvement in short-term pain scores at 1 month postinjection but no longer term improvement at 3, 6, or 12 months after injection.24 That review concluded that intradiscal steroid injection should only be used as a short term

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bridge therapy, as it does not appear to provide long-term relief.

Conclusion Despite the study of intradiscal injection for the treatment of discogenic back pain spanning more than 6 decades, there remains no clear consensus or strong evidence supporting

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intradiscal injection as a definitive treatment option. Additional large, thoughtfully crafted, randomized controlled trials are needed to determine whether any of the biologic or non-biologic intradiscal therapies previously described may serve as effective and durable therapies for the treatment of discogenic back pain. l

References 1. DePalma MJ, Ketchum JM, Saullo T. What is the source of chronic low back pain and does age play a role?

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2. Ohtori S, Inoue G, Miyagi M, Takahashi K. Pathomechanisms of discogenic low back pain in humans and animal models. Spine J. 2015;15(6):1347-1355.

3. Schneider BJ, Hunt C, Conger A, et al. The effectiveness of intradiscal biologic treatments for discogenic low back pain: a systematic review.

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4. Akeda K, Ohishi K, Masuda K, et al. Intradiscal injection of autologous platelet-rich plasma releasate to treat discogenic low back pain: a preliminary clinical trial.

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5. Comella K, Silbert R, Parlo M. Effects of the intradiscal implantation of stromal vascular fraction plus platelet rich plasma in patients with degenerative disc disease. J Transl Med. 2017;15(1):12.

6. Coric D, Pettine K, Sumich A, Boltes MO. Prospective study of disc repair with allogeneic chondrocytes presented at the 2012 Joint Spine Section Meeting.

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7.

Kumar H, Ha DH, Lee EJ, et al. Safety and tolerability of intradiscal implantation of combined autologous adipose-derived mesenchymal stem cells and hyaluronic acid in patients with chronic discogenic low back pain: 1-year follow-up of a phase I study. Stem Cell Res Ther. 2017;8(1):262.

8. Levi D, Horn S, Tyszko S, Levin J, Hecht-Leavitt C, Walko E. Intradiscal platelet-rich plasma injection for chronic discogenic low back pain: preliminary results from a prospective trial.

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Pain Med. 2016;17(6):1010-1022.

9. Navani A, Hames A. Platelet-rich plasma injections for lumbar discogenic pain: a preliminary assessment of structural and functional changes. Tech Reg Anesth Pain Manage. 2015;19(1-2):38-44.

10. Noriega DC, Ardura F, Hernandez-Ramajo R, et al. Intervertebral disc repair by allogeneic mesenchymal bone marrow cells: a randomized controlled trial.

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11. Orozco L, Soler R, Morera C, Alberca M, Sanchez A, Garcia-Sancho J. Intervertebral disc repair by autologous mesenchymal bone marrow cells: a pilot study.

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12. Pettine KA, Suzuki RK, Sand TT, Murphy MB. Autologous bone marrow concentrate intradiscal injection for the treatment of degenerative disc disease with three-year follow-up. Int Orthop. 2017;41(10):2097-2103.

factors associated with the treatment outcomes of intradiscal platelet-rich plasma-releasate injection therapy for patients with discogenic low back pain.

Medicina (Kaunas). 2023;59(4):640.

17. Smith L. Enzyme Dissolution of the nucleus pulposus in humans.

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18. Ishibashi K, Iwai H, Koga H. Chemonucleolysis with chondroitin sulfate ABC endolyase as a novel minimally invasive treatment for patients with lumbar intervertebral disc herniation. J Spine Surg. 2019;5(Suppl 1):S115-S121.

19. Zhang F, Wang S, Li B, Tian W, Zhou Z, Liu S. Intradiscal injection for the management of low back pain.

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20. Alda M. Methylene blue in the treatment of neuropsychiatric disorders.

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13. 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; quiz 10.

21. Li JW, Wang RL, Xu J, et al. Methylene blue prevents osteoarthritis progression and relieves pain in rats via upregulation of Nrf2/PRDX1. Acta Pharmacol Sin. 2022;43(2):417-428.

14. Wolff M, Shillington JM, Rathbone C, Piasecki SK, Barnes B. Injections of concentrated bone marrow aspirate as treatment for discogenic pain: a retrospective analysis.

BMC Musculoskelet Disord. 2020;21(1):135.

22. Guo X, Ding W, Liu L, Yang S. Intradiscal Methylene blue injection for discogenic low back pain: a meta-analysis. Pain Pract. 2019;19(1):118-129.

15. Her YF, Kubrova E, Martinez Alvarez GA, D’Souza RS. The analgesic efficacy of intradiscal injection of bone marrow aspirate concentrate and culture-expanded bone marrow mesenchymal stromal cells in discogenic pain: a systematic review. J Pain Res. 2022;15:3299-3318.

16. Akeda K, Fujiwara T, Takegami N, Yamada J, Sudo A. Retrospective analysis of

23. Cao P, Jiang L, Zhuang C, et al. Intradiscal injection therapy for degenerative chronic discogenic low back pain with end plate Modic changes.

Spine J. 2011;11(2):100-106.

24. Mishra P, Goyal S, Makker R. Intradiscal steroid therapy in chronic discogenic pain: a systematic review of literature.

Palliat Med Pract. 2023;17(3):152-163.

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