When is a spine fused?

Injury, Int. J. Care Injured 42 (2011) 306–313

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When is a spine fused? Christina Goldstein *, Brian Drew McMaster University Department of Surgery, Division of Orthopaedics, Hamilton Health Sciences – General Site, 6 North Trauma, 237 Barton Street East, Hamilton, Ontario, Canada L8L 2X2

A R T I C L E I N F O

A B S T R A C T

Article history: Accepted 12 November 2010

The ability to correctly diagnose spinal non-union is vital to our ability to diagnose and treat patients with new or recurrent symptoms following spine fusion and to accurately assess the efficacy of spine fusion techniques and technologies. Surgical exploration has traditionally been the gold-standard investigation for spinal non-union. As routine surgical exploration is impractical in the majority of patients the use of non-invasive radiologic methods of spine fusion assessment is necessary. The purpose of this paper is to outline the most common radiologic methods of spine fusion assessment including the strengths and limitations associated with each imaging modality. In addition we will review the bestavailable evidence for the use of radiologic investigations to diagnose spine non-unions. We will then provide recommendations for what we believe to be the best methods of diagnosing successful union of cervical interbody, lumbar interbody and lumbar posterolateral fusions that can be used by spine clinicians and researchers alike. ß 2010 Elsevier Ltd. All rights reserved.

Keywords: Spinal fusion Lumbar Interbody Posterolateral ACDF Assessment Outcome Radiology

Introduction Since its introduction in 1911 by Albee1 for the treatment of tuberculosis of the spine, the indications for lumbar spinal fusion have expanded to include degeneration, trauma, neoplasm, infection deformity and congenital abnormalities.39 Following its description by Robinson and Smith,45 anterior cervical decompression and fusion (ACDF) has become a reliable method of treating radicular and myelopathic symptoms of cervical spine trauma, stenosis and spondylosis.8 With recent advances in fusion technique and instrumentation design spinal fusion is generally a successful procedure. However, up to 50% of cervical8 and lumbar spine fusions30 may result in a non-union. This may be due to surgical factors, including the number of levels fused, choice of graft and use of instrumentation, or patient factors, such as smoking, diabetes and use of medications including non-steroidal anti-inflammatories and steroids.28,30,53 Though spinal non-union does not necessarily equate to clinical failure,2,40 the ability to accurately diagnose spinal non-union is of paramount importance, allowing spine care clinicians and researchers to properly diagnose and treat symptomatic patients following fusion procedures and to accurately assess the efficacy of new technologies designed to improve spine fusion surgery.

Surgical exploration is generally accepted to be the gold standard method of diagnosing spinal non-union.34,43 This is impractical in the majority of cases and as such non-invasive methods of diagnosing spinal non-union are required. Consensus regarding the best non-invasive way to assess spine fusion healing does not exist.34 Multiple radiologic investigations including static and dynamic radiographs, computed tomography (CT) and magnetic resonance imaging (MRI)8,10,12,18,20,26,41,44,48,49 have been used to assess the status of spine fusion and a wide variety of criteria for successful fusion have been employed.59 The goal of this summary article is to outline the most commonly used methods of radiologic assessment of cervical and lumbar spine fusion as well as to address issues with their use in the diagnosis of spine non-union. In addition we will present information regarding the diagnostic accuracy of these investigations in hopes of identifying the best method of diagnosing nonunion of anterior cervical, posterolateral lumbar and lumbar interbody spinal fusions based on the current literature. Though the diagnosis of spinal non-union is rarely made using diagnostic imaging alone, a review of the historical and physical examination findings of spinal non-union is beyond the scope of this paper. Methods of spine fusion assessment Static radiographs

* Corresponding author. Tel.: +1 905 928 8290; fax: +1 905 523 6776. E-mail addresses: [email protected] (C. Goldstein), [email protected] (B. Drew). 0020–1383/$ – see front matter ß 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.injury.2010.11.041

Static anteroposterior (AP) and lateral radiographs are the most common method of fusion assessment for both the lumbar and the cervical spine.30,39 The main advantages of static radiographs

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Fig. 1. AP radiographs of a posterolateral L4-S1 instrumented fusion with autogenous iliac crest bone graft at (A) 1 month, (B) 6 months and (C) 24 months post-operatively. With progressive consolidation the pebble-like appearance of the bone graft is lost and trabeculated bone bridging the transverse processes is visualized.

include their widespread availability, low cost and the low dose of radiation required to obtain them. Though static radiographs are rarely obtained in isolation a significant amount of information may be garnered from them regarding the healing status of spine fusions. In posterolateral fusions of the lumbar spine the AP radiograph typically shows progressive consolidation and loss of the pebblelike appearance of bone graft in the lateral gutters between 6 and 12 weeks (Fig. 1).21 Bridging trabeculated bone between the transverse processes of the intended fusion levels is considered a sign of union54 while bone graft resorption may signal a delayed or non-union.21 Though not 100% specific, fatigue failure of posterior spinal instrumentation including screws and rods is suggestive of non-union.21,39 Post-operative radiolucencies, or ‘‘clear-zones’’, around pedicle screws are also associated with non-union,39 especially when the number or size of the lucencies increases over time or they persist for 2 years or more following the fusion procedure.58 Failure of union following anterior or posterior lumbar interbody fusions may be diagnosed by visualization of a gap between the graft or cage and vertebral endplates.39 Plain radiographs may also be used to assess the device–bone interface looking for periimplant sclerosis and migration or subsidence of the implant which may also be signs of delayed or non-union.9 Successful lumbar interbody union is suggested by the presence of trabecular bone bridging the inferior and superior endplates anterior, posterior and lateral to the interbody device(s).9 Though increasing density within an interbody device may be observed on serial imaging, plain radiographs have been shown to lack sensitivity for detecting intraimplant bone.13 In general, the lateral image is best for visualizing bridging new bone formation and implant migration. Following anterior cervical spine fusion the most common criteria for fusion on static radiographs is bony trabeculae bridging the graft–vertebral body interface.59 Other signs of successful union include evidence of graft remodeling, maintenance of graft height and disappearance of posterior osteophytes.53,59 The most common plain radiographic finding of cervical non-union is lucency at the graft–bone or cage–bone interface.53 Finally, while a rare outcome of instrumented anterior cervical fusions with modern implants catastrophic plate failure is also highly predictive of non-union.53 Though widely used in clinical practice and the spine literature, and despite their multiple advantages over other imaging modalities, static radiographs are not a perfect tool for diagnosing spinal non-union. The presence of instrumentation for fusion stabilization may obscure the fusion mass and make it difficult to assess.30,39 This is of particular concern in lateral images of posterolateral instrumented fusions of the lumbar spine. The limitations of static radiographs as a two-dimensional representation of spinal fusion, ultimately a three-dimensional process, also limit their utility in diagnosing spinal non-union, as overlapping

regions of new bone formation may mask fine gaps in the fusion mass leading radiographs to be incorrectly interpreted as demonstrating successful fusion.48 Finally, except in the cases of radiolucent cages, plain radiographs do not allow visualization of bone within the cage construct in interbody fusions4,13,15,49 and are therefore unable to diagnose locked pseudarthroses in interbody fusions, non-unions in which bone grows from each endplate into the cage but fails to unite within it.18 Dynamic radiographs Since Cleveland and colleagues advocated the use of biplanar dynamic radiographs to assess fusion of the lumbosacral spine14 they have become a common method of diagnosing spinal nonunion. Bending films in both the coronal and the sagittal planes may be obtained though lateral flexion–extension radiographs are more frequently used. The rationale behind dynamic radiographs as a means to diagnose non-union lies in the theory that solidly fused spinal segments will not exhibit any residual motion. Though flexion–extension radiographs are widely used in the literature to assess both cervical and lumbar spine fusions multiple issues regarding their use, including imaging technique, measurement technique, measurement error, the effect of instrumentation on spinal motion and disagreement regarding cutoffs for acceptable motion, influence their utility as a diagnostic tool for detecting spinal non-union. Lateral flexion–extension radiographs may be obtained in the standing, seated or supine position. While standing static radiographs have been advocated to potentially unmask subtle sagittal or coronal plane instability, standing dynamic radiographs may not be reliable as it is difficult to position the X-ray beam perpendicular to the level of interest and standing allows a significant amount of motion to occur through the pelvis and hips which can alter the segmental motion of the lumbar spine.9,36,37,42 Supine bending radiographs suffer from the same shortcomings. Thus it has been recommended that lateral flexion–extension radiographs of the lumbar spine be taken with the patient in the seated position to facilitate X-ray beam positioning and lock the pelvis during patient movement. Different amounts of spinal motion may also be observed depending on the method used to quantify angular motion on plain radiographs. Three different methods have been described for measuring angular deformity in flexion–extension radiographs, the Cobb method,35 Hutter method23 and the Simmons method.51 In the Hutter method, used more commonly by radiologists, the flexion and extension radiographs are superimposed and angular motion between the two images is determined to be either present or absent.23 Simmons described measuring vertebral motion by drawing a line down the front of the vertebral bodies of the involved vertebrae and measuring the angle created by their intersection (Fig. 2A).51 Changes in this angle between flexion and extension films are quantified to determine the presence or

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Fig. 2. Methods of assessment of intervertebral motion in the cervical spine: (A) the Simmons method using anterior vertebral body lines, (B) the Cobb method using lines perpendicular to the upper and lower endplates of the cranial and caudal vertebra, respectively and (C) the interspinous method.

absence of union. In the Cobb method lines are drawn along the superior and inferior endplates of the most cranial and caudal vertebrae of the fused segments and the angle created by the intersection of two lines drawn perpendicular to the endplates is measured (Fig. 2B),35 with changes in this angle representing union or non-union. Compared to CT scanning the Hutter method and Simmons method have been shown to lead to significantly higher fusion rates in anterior lumbar interbody fusions.48 Instead of measuring angular changes on flexion–extension radiographs, others have used changes in interspinous distance to diagnose spinal non-union (Fig. 2C), most frequently in the cervical spine.10,16,17,41,60 Failure to obtain fusion has been defined as an increase in the distance between two constant points on adjacent spinous processes greater than 0 mm,52 1 mm8,16,17 and 2 mm.10,41 Measurement of interspinous motion may be more accurate than intervertebral angular measurements for determination of spinal fusion.10 However, the ability to reliably measure such small distances is questionable,55 likely due to differences in marking landmark points,57 and this method cannot be used in patients who have undergone previous laminectomy. Regardless of the method used to determine motion on flexion– extension radiographs, the diagnostic accuracy of this investigation is dependent on the amount of motion used to define nonunion.20,22,48 Defining spinal non-union based on intervertebral motion is limited by the absence of normative data regarding motion following spinal fusion and disagreement in the maximum allowable motion following successful fusion.34 A recent cadaver study of motion following simulated lumbar spinal fusion revealed 13  4 degrees of motion following intertransverse fusion, 5  3 degrees after posterior facet fusion and 3  2 degrees with anterior interbody fusion with a plate.5 Finite element analysis of motion in simulated lumbar spine fusion has shown a wide range of sagittal angular motion from 0.8 to 3.3 degrees for a complete anterior lumbar interbody fusion to 2.0–6.0 degrees for unilateral and bilateral intertransverse process fusions, respectively.6 A cadaveric study of lumbar interbody fusion has shown virtually no residual motion at the fused level31 while Luk et al.33 showed an average of 2 degrees of motion at L4-5 following L4-5 anterior lumbar interbody fusion (ALIF) and approximately 1.5 and 0 degrees of motion at L4-5 and L5-S1 following two-level L4-S1ALIF in their in vivo study. In the cervical spine radiostereometric analysis (RSA) of motion following ACDF has shown less than 1.5 degrees of motion in 80% of unions and greater than 1.5 degrees of motion in 60% of non-unions.38 However, the diagnosis of union in this study was made using plain radiographs rather than the gold standard of surgical exploration. Computed tomography CT scans have been used to diagnose spinal non-union since their introduction in the 1970s.44 Compared to fusion assessment

using plain radiographs CT offers many advantages. CT scans provide increased bony definition and more detailed information regarding the location and status of the fusion mass in both cervical and lumbar fusions. They also provide a more thorough assessment of peri-implant lucencies and bone formation within interbody devices.9 As a result of these advantages over radiography CT scans have become a very common tool to assess spine fusions and may be considered the preferred method of diagnosing spinal non-union.9,24,39 Similar to plain radiographs, the demonstration of continuous trabecular bone bridging the transverse processes in posterolateral fusions and vertebral body endplates in cervical and lumbar interbody fusions indicates successful union. Despite its advantages the use of CT to determine spinal fusion status is associated with several potential disadvantages including increased cost, higher doses of patient radiation and more limited availability. Metallic cages or instrumentation may also create significant artifact precluding the accurate interpretation of CT scans following spinal fusion.29,30 It has also been shown that plain axial images may also fail to reveal transverse clefts in a fusion mass leading to an incorrect diagnosis of successful union (Fig. 3). As a result, in 1976 Brodsky and colleagues concluded that axial CT scans were insufficiently accurate to determine the healing status of posterolateral spine fusions.7 Since these early studies changes in implants and imaging technology have resulted in increased diagnostic accuracy of CT scans in diagnosing spinal non-union. The movement from stainless steel to titanium implants has resulted in less image distortion and artifact due to its decreased density and lessened ability to attenuate the X-ray beam.32 Improvements in CT software further allows for the selection of image reconstruction parameters such that artifact created by metallic implants is minimized.56 The development of spiral CT scan which allows for the rapid acquisition of thin-slice images has also allowed for the creation of multiplanar and 3-dimensional reformatted images.21 CT scans, including sagittal, coronal and 3D reconstructions, have been shown to provide more information regarding spine fusion status compared to plain radiographs and are associated with lower union rates.16,27,41,46,48–50,60 Evidence for spine fusion assessment The ideal method to determine the accuracy of radiologic investigations in detecting spine non-union is a trial in which patients in whom spinal non-union is suspected are randomized to treatment groups based on the results of a new diagnostic test or surgical exploration with the outcomes of the two groups being compared. This type of trial is not feasible due to the potentially unfavorable risk benefit ratio associated with surgical exploration in the absence of a spinal non-union and as a result no such trial has been performed.

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Fig. 3. CT scan images of an instrumented posterolateral L2-S1 fusion. The patient presented with mechanical low back pain 15 months following the index surgery. Axial images (A) demonstrate what appears to be bridging bone at L4-5. Sagittal (B) and coronal (C) reconstructions clearly demonstrate the transverse non-union at L4-5.

The next best method of determining diagnostic accuracy is to prospectively examine the results of a new diagnostic test compared to those of surgical exploration in a cohort of patients. While multiple studies examining the utility of a variety of imaging modalities in diagnosing non-union of the cervical and lumbar spine have been conducted this paper will focus on the results of this type of cohort study as the highest level of evidence in support of the use of radiologic investigations in the diagnosis of spinal non-union. The results of studies of the reliability of diagnostic imaging in the diagnosis of cervical and lumbar spine non-union will also be presented. Cervical interbody fusion Multiple prospective and retrospective cohort studies have examined the reliability and diagnostic accuracy of radiographs and CT in assessing for cervical spine non-union following ACDF or corpectomy.8,10,16,19,20,41,52,59 To our knowledge only three have compared the results of diagnostic imaging to direct surgical exploration (Table 1).8,10,20 Ghiselli and colleagues (2006) compared the results of intraoperative exploration during posterior spinal fusion for pseudarthrosis with those of flexion–extension radiographs and CT scans in a cohort of symptomatic patients following single-level ACDF.20 Using a cutoff of 4 degrees of angular motion to define pseudarthrosis flexion–extension radiographs showed a positive predictive value (PPV) of 100% but negative predictive value (NPV) of 57%. These values improved to a PPV of 100% and NPV of 79% when the definition of pseudarthrosis was changed to 1 degree of motion. CT scan alone was found to have a PPV of 100% and NPV of

73% though the criteria for determination of successful fusion were not reported. A combination of flexion–extension radiographs (with a diagnostic cutoff of 1 degree of motion) and a CT scan was found to be the most accurate method of diagnosing non-union with a PPV of 100% and NPV of 92%. More recently Buchowski et al. performed surgical exploration of the fusion mass of 14 consecutive patients who had undergone single-level ACDF an average of 6 months following their primary procedure.8 All patients underwent AP, lateral and flexion– extension radiography and thin-slice (1.5 mm) CT scanning within a month of their second surgical procedure. Union was defined by bridging trabeculae and less than 1 mm of interspinous motion on static and dynamic radiographs and bridging trabeculae with no lucencies at the graft–bone interface on the sagittal and coronal CT reconstructions. At anterior surgical exploration six patients were found to have a solid fusion while eight were deemed to have a non-union. Based on the assessments of three independent surgeon raters the plain radiographs were found to agree with the intraoperative assessment 81% of the time (range 71.4–92.8%) while the CT scans agreed in 83.3% of the cases (range 78.6–85.7%). While CT scans and plain radiographs thus appear to be equally accurate in diagnosing cervical non-union the interrater reliability was found to be lower for plain radiographs than for CT scans (kvalue 0.31–0.55 for radiographs compared to 0.73–0.87 for CT scans), a finding that has also been observed in the lumbar spine.11 In their retrospective cohort study of 29 ACDF procedures in 27 patients Cannada et al. observed a higher rate of correlation between flexion–extension radiographs and static AP and lateral radiographs when non-union was defined as a greater than 2 mm change in interspinous distance compared to angular motion >2

Table 1 Cervical interbody fusion reliability studies. Study

Design

Investigations

Results

Buchowski et al.8

Prospective cohort involving 14 patients an average of 6 months following ACDF

Cannada et al.10

Retrospective cohort involving 29 ACDF levels in 27 patients

Ghiselli et al.20

Cohort of patients with symptoms 1 year following ACDF

Surgical exploration within 1 month of imaging compared to plain radiographs (bridging trabeculae and <1 mm of motion) and CT scan (1.5 mm cuts with sagittal and coronal reconstructions; bridging trabeculae with no lucencies at the graft–bone interface) Lateral flexion–extension radiographs showing >2 mm increase in interspinous distance or >2 degrees of motion as measured using the Cobb method compared to AP/lateral radiographs demonstrating mature, bridging bony trabeculae across the disc space. Surgical exploration in 5 patients Surgical exploration during posterior cervical fusion compared to flexion–extension radiographs (>1 degree of motion or >4 degrees of motion) and CT scans

81% agreement (71.4–92.8%) between radiographs and surgical exploration and 83.3% agreement (78.6–85.7%) between CT and surgery. Higher interobserver agreement for CT scans (mean k = 0.82) than radiographs (mean k = 0.46) Interspinous method gave a sensitivity of 0.89 and specificity of 0.91 for diagnosing non-union. Cobb method gave values of 0.82 and 0.39 for sensitivity and specificity. Higher correlation between diagnosis with interspinous method (Pearson’s r = 0.77) versus Cobb method (Pearson’s r = 0.28) Improved specificity of flexion–extension radiographs using 1 degree cutoff compared to 4 degrees (PPV 100% for both; NPV 57% for 4 degrees and 79% for 1 degree). CT alone showed a PPV of 100% and NPV of 73%. Combining the investigations gave a PPV of 100% and NPV of 92% thus increasing the specificity of diagnosing non-union

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degrees as measured by the Cobb method (Pearson’s correlation co-efficient 0.77 versus 0.28).10 Though the diagnostic sensitivity of both methods was found to be similar, 0.89 and 0.82 for the interspinous method and Cobb method, respectively, the interspinous method of diagnosing non-union was found to be much more specific at 0.91 compared to 0.39. Based on these results the authors concluded a change in interspinous distance >2 mm to be more accurate at diagnosing cervical non-union following ACDF than an increase of angular motion >2 degrees. However, these results were obtained using bridging trabeculae crossing the disc space on static radiographs as the diagnostic gold standard rather than surgical exploration which was only performed in 5 of the 27 patients. Lumbar interbody fusion A wide variety of individual criteria, and combinations thereof, have been proposed by which to judge the union status of lumbar interbody fusions. These include, but are not limited to, varying degrees of angular motion or translation on flexion–extension radiographs, absence of radiolucencies surrounding implants and bridging bone between vertebral endplates. Consensus regarding the definition of successful radiographic fusion and the best diagnostic imaging modality to assess lumbar interbody fusions does not exist.34 This is likely due, at least in part, to the paucity of reliability and validity data regarding imaging diagnosis of spinal non-unions. Two recent cohort studies have examined the results of fusion assessment using CT and CT and radiographs compared to direct surgical exploration (Table 2).12,18 Carreon et al. performed posterior (n = 44) or anterior and posterior (n = 45) surgical exploration on 49 patients who had undergone ALIF with metallic cages.12 The fusion status at surgery was compared to the diagnosis of fusion made with fine-cut CT with sagittal and coronal reconstructions with fusion being defined by one of three methods: (1) bone within and around the cage, (2) presence of an anterior ‘‘sentinel sign’’, or (3) presence of a posterior ‘‘sentinel sign’’. CT scans showed a sensitivity of 0.7–0.97 and specificity from 0.28 to 0.85 when considering bone within and around the disc space with a kappa coefficient of 0.23 for interobserver reliability. The interobserver reliability in detection of a sentinel sign was low to fair with kappa values of 0.34 and 0.23 for an anterior and posterior sentinel sign, respectively. These radiographic signs were determined to be a poor marker for successful interbody fusion with only 20% of fused levels showing an anterior sentinel sign and 33–87% of levels showing a posterior sentinel sign depending on the observer. Fogel and colleagues (2008) used a posterior surgical approach to diagnose successful fusion in 90 consecutive patients with 172 levels fused by PLIF and posterolateral fusion.18 All patients had

preoperative AP, lateral and Ferguson radiographs and 54 patients also underwent CT-scanning. On both of these modalities successful interbody fusion was defined as bridging bone between vertebral endplates filling half of the fusion area. Compared to an earlier study demonstrating decreased ability to visualize peri-implant and intraimplant bone using plain radiographs in the presence of titanium interbody cages,49 Fogel et al. demonstrated excellent sensitivity (100%) and similar values of specificity for plain radiographs and CT scans (0.89 and 0.86, respectively) in diagnosing non-union of PLIF in the presence of radiolucent cages.18 Using thin-slice CT scans with sagittal and coronal reconstruction as their diagnostic ‘‘gold standard’’ Santos et al. examined the ability of plain radiographs and flexion–extension radiographs to diagnose ALIF union.48 Two different methods of assessing intervertebral motion with three different motion cut-offs were used to determine fusion on the dynamic radiographs. Except in the case of using the Simmons method to measure intervertebral motion with a cutoff for successful fusion of <2 degrees, dynamic radiographs tended to over-estimate the presence of successful fusion compared to CT scans. The lowest level of agreement between the imaging modalities was with flexion–extension radiographs using the Simmons method and the FDA motion cut-off of 5 degrees (61%). The highest percent agreement of 71% was between CT scans and flexion–extension radiographs demonstrating no motion using the Hutter overlap method. Lumbar posterolateral fusion Posterolateral fusion is the most commonly performed type of fusion performed in the lumbar spine.47 As a result, more investigations have been performed regarding the diagnostic utility of radiologic investigations in posterolateral spine fusion assessment compared to cervical and lumbar interbody fusion. We recently reviewed the spine literature and identified five studies comparing the diagnosis of non-union of posterolateral fusion of the lumbar spine using radiographs and CT scans versus surgical exploration (Table 3).3,7,11,25,29 In the first available cohort study examining fusion assessment with radiologic investigations compared to surgical exploration Brodsky and colleagues examined the preoperative imaging of 175 patients undergoing surgical exploration following posterolateral fusion of the lumbar spine.7 While bending radiographs were found to be more sensitive than plain radiographs and CT scans in diagnosing non-union (0.96 versus 0.89 and 0.63, respectively), CT scans were shown to have a higher specificity (0.86 versus 0.6 for static radiographs and 0.37 for bending radiograph). As a result of their similar positive and negative predictive values Brodsky et al. concluded all three imaging modalities to be insufficiently accurate to determine the solidity of posterolateral lumbar fusions.7 However, it is important to note that two significant

Table 2 Lumbar interbody fusion reliability studies. Study

Design

Investigations

Results

Carreon et al.

Prospective cohort of 49 patients undergoing ALIF with metallic cages

Surgical exploration and fine-cut CT with sagittal and coronal reconstructions. Fusion determined by considering the disc space around and within the cages as well as presence of the anterior and posterior ‘‘sentinel signs’’, fusion across the anterior and posterior margins of the disc space

Fogel et al.18

Retrospective cohort of 172 fusion levels in 90 consecutive patients following PLIF with radiolucent cages and posterolateral fusion

Surgical exploration compared to AP, lateral and Ferguson radiographs and thin-slice CT scan (n = 54; 1mm cuts with sagittal and coronal reconstructions) looking for bone bridging at least half of the fusion area for the PLIF for fusion to be present

Interobserver variability in fusion determination using CT scans showed a kappa of 0.25 (p < 0.0001) with sensitivity of 0.7–0.97 and specificity from 0.28 to 0.85. Poor reliability in detection of ‘‘sentinel sign’’ (anterior k = 0.34, posterior k = 0.23) with variable sensitivity and specificity (anterior 0.20 and 0.92, respectively, posterior 0.67 and 0.79, respectively) Sensitivity of XR and CT in diagnosing non-union was 100%. Specificity was similar for the two with values of 0.89 and 0.86 for radiographs and CT, respectively

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Table 3 Lumbar posterolateral fusion reliability studies. Study

Design

Investigations

Results

Blumenthal and Gill

Cohort study of 49 patients undergoing hardware removal following interbody and instrumented posterolateral fusion

Surgical exploration versus AP and lateral radiographs. No definition for successful fusion provided

Brodsky et al.7

Retrospective cohort study involving 174 patients following posterolateral spine fusion

Surgical exploration versus preoperative AP, lateral and oblique radiographs, biplane bending radiographs (n = 64) and CT scans (n = 42; 3-mm axial cuts). No definitions for successful fusion provided

Carreon et al.11

Retrospective cohort study of 163 levels in 93 patients who had undergone instrumented posterolateral lumbar fusion

Surgical exploration compared to thinslice (1 mm) CT with axial and coronal reconstructions looking for continuous trabeculated bone connecting the transverse processes

Kant et al.25

Retrospective cohort study of 75 patients with instrumented posterolateral spine fusions

Larsen et al.29

Prospective cohort study of 25 consecutive patients undergoing surgical exploration following instrumented posterolateral lumbar fusion

Surgical exploration compared to AP, lateral, oblique and Ferguson radiographs demonstrating bridging bone between the transverse processes and obliteration of the facet joints Surgical exploration compared to AP, lateral and oblique radiographs (n = 21; bridging bony trabeculae), lateral flexion–extension radiographs (<3 degrees of motion) and CT scans (n = 24; 5-mm thick overlapping cuts with sagittal and coronal reconstructions; bridging bony trabeculae)

Intraobserver agreement gave a kappa of 0.42–0.72. Wide ranges in sensitivity (0.49–0.81, mean = 0.72) and specificity (0.25–1.0, mean = 0.58). Overall correlation of 69% between radiographic diagnosis and surgical exploration Biplane bending films showed the lowest specificity (0.37) but highest sensitivity for the diagnosis of nonunion (0.96). Plain radiographs performed moderately well with a sensitivity of 0.89 and specificity of 0.60. CT scans showed the highest specificity (0.86) but lowest sensitivity (0.63) for detecting non-union Substantial interobserver agreement for posterolateral gutter fusion (Cohen’s k = 0.62). When both posterolateral gutters were read as fused the likelihood ratio of fusion at surgery was 8.31 (positive predictive value 0.89). When neither gutter was read as fused a non-union was 2.9 times more likely to be found at surgery Overall agreement between surgical exploration and radiographs was poor with a mean kappa of 0.26 (range 0.14–0.59, 95% CI 0.07–0.44). Sensitivity for a diagnosis of successful fusion was 0.85 with a specificity of 0.38.

3

limitations affect the interpretation of these findings: (1) criteria for successful radiologic fusion were not provided for any of the investigations performed and (2) CT scans were limited to axial cuts without sagittal and coronal reconstructions. In a similar study Blumenthal and Gill examined the diagnostic accuracy of plain radiographs in diagnosing spinal non-union.3 An average of 9 months following interbody and instrumented posterolateral spine fusion elective hardware removal was performed in 49 patients at which time the posterolateral fusion mass was explored. Fusion status at surgical exploration was compared to the findings of preoperative AP and lateral radiographs assessed by four blinded observers. The criteria for successful fusion were not defined. Intra-observer variability showed a Cohen’s kappa of 0.42–0.72 following two readings of the radiographs 3 months apart. Wide ranges of sensitivity and specificity were observed, though the mean values of 0.72 and 0.58, respectively, were similar to those reported by Brodsky et al.7 Kant et al. also studied the utility of radiographs in assessing the healing status of posterolateral spine fusions with or without an interbody fusion.25 Surgical exploration was performed of 75 instrumented posterolateral fusions involving 126 vertebral levels. The patient was designated radiographically fused when AP, lateral, oblique and Ferguson radiographs demonstrated solid bone between the transverse processes or obliteration of the facet joints. Wide ranges in the agreement between the radiographs and surgical exploration were observed depending on the level fused (k = 0.03–0.59) with the lowest agreement at L3-4 and the highest at L5-S1. The overall agreement was poor (k = 0.26). Though the sensitivity was reasonable at 0.85 the specificity of the radiographs in diagnosing successful fusion was low at 0.38 with a false positive rate for fusion of almost 20%. A year later, Larsen et al. also examined the assessment of instrumented posterolateral spine fusions with plain AP, lateral and oblique radiographs, but they included comparisons of the findings of lateral flexion–extension radiographs and CT scans with sagittal and coronal reconstructions to those of direct surgical

Sensitivity and specificity of plain radiographs was 0.42 and 0.89, respectively, for flexion–extension radiographs was 0.86 and 0, and for CT scans was 0.53 and 0.78

exploration.29 Their prospective cohort of 25 consecutive patients found sensitivities and specificities of 0.42 and 0.89 for plain radiographs, 0.86 and 0 for flexion–extension radiographs and 0.53 and 0.78 for CT scans, respectively. The authors were unable to generate any statistically significant data regarding the presence or absence of fusion, leading them to conclude that plain radiographs, flexion–extension radiographs and CT scans were not accurate in their evaluation of fusion status. The most recent study of posterolateral spine fusion assessment compared the findings of surgical exploration of 163 fused levels in 93 patients with those of thin-slice (1 mm) CT scans with sagittal and coronal reconstructions.11 Successful posterolateral fusion as determined by the CT scan was defined as continuous trabeculated bone connecting the transverse processes. Fusion assessment with the CT scans showed substantial interobserver agreement (k = 0.62). In contrast to the earlier findings of Brodsky et al.,7 Carreon and colleagues found CT scans to be quite accurate in diagnosing successful union.11 When fusion was defined as one or both gutters fused the sensitivity of CT scans for non-union was shown to be 0.91 and specificity was 0.69, resulting in a negative predictive value of 97%.11 Recommendations Cervical interbody fusion Based on the current literature lateral flexion–extension radiographs appear to be an adequate method of screening for cervical non-union with successful fusion being defined as bridging trabeculae across the disc space, the absence of lucencies at the graft–bone or implant–bone interface8,16 and <2 mm of interspinous motion.10 In the setting of persistent or recurrent symptoms following the primary fusion procedure, the increased interobserver agreement,8,41 increased specificity of CT scans20 and ability of sagittal and coronal reconstructions to ‘‘see’’ bone within hollow metallic implants leads us to recommend the use of

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thin-slice CT with sagittal and coronal reconstruction as the primary diagnostic modality. Lumbar interbody fusion We recommend assessment of lumbar interbody fusion using both static and dynamic imaging modalities. We agree with the conclusions of Burkus et al.9 that lateral flexion–extension radiographs obtained with the patient in the seated position should demonstrate no intervertebral motion. When radiolucent cages have been used, and in the absence of clinical symptoms, standard AP and lateral radiographs appear to be adequate to assess for intraimplant and peri-implant bone bridging the superior and inferior vertebral endplates. In the setting of persistent or recurrent symptoms, or when metallic cages have been implanted, a thin-slice (2 mm) CT scan with sagittal and coronal reconstructions should be obtained to examine for the presence of bridging bone and rule out a locked pseudarthrosis. Lumbar posterolateral fusion Given the lack of normative data regarding acceptable motion following instrumented posterolateral fusions of the lumbar spine, a consensus definition of successful fusion based on lateral flexion– extension radiographs does not exist. Thus we cannot currently recommend their use to diagnose non-union of instrumented lumbar posterolateral fusions. In asymptomatic patients plain AP and lateral radiographs demonstrating trabeculated bone bridging the transverse processes, with an absence of signs of non-union including failure of hardware and peri-implant ‘‘clear zones’’ 2 years following fusion, appears adequate for diagnosing successful fusion. In the presence of radiographic findings suggestive nonunion or new or recurrent symptoms following posterolateral spine fusion we recommend thin-slice (1 or 2 mm) CT scanning with sagittal and coronal reconstructions to more accurately assess the integrity of the fusion mass. We also recommend that thin-slice CT scans with sagittal and coronal reconstructions, with their higher sensitivity, specificity and inter- and intraobserver reliability11,12 be used in the research setting if absolute union rate is the primary outcome. Conclusions While surgical exploration appears to remain the gold standard investigation, the diagnosis of non-union of a cervical or lumbar spine fusion may be made using radiologic imaging. However, a universal method of screening for non-union following different types of fusions in different regions of the spine does not exist. Though we have presented recommendations for what we believe to be the best non-invasive methods of fusion assessment for cervical interbody, lumbar interbody and posterolateral lumbar fusions in the clinical setting, the results of these investigations must be interpreted in light of the findings of a thorough history and physical examination to determine the clinical significance of the diagnosis of non-union and the best treatment option for each individual patient. Role of the funding source No funding was obtained for the preparation of this invited submission. Conflict of interest Neither Dr. Goldstein nor Dr. Drew has any financial or personal relationships to disclose.

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