Surgical Treatment Strategies for High-Grade Spondylolisthesis: A Systematic Review
===================================================================================

* Peter G. Passias
* Caroline E. Poorman
* Sun Yang
* Anthony J. Boniello
* Cyrus M. Jalai
* Nancy Worley
* Virginie Lafage

## Abstract

**Background** HGS is a severe deformity most commonly affecting L5-S1 vertebral segment. Treatment available for HGS includes a range of different surgical options: full or partial reduction of translation and/or abnormal alignment and in situ fusion with or without decompression. Various instrumented or non-instrumented constructs are available, and surgical approach varies from anterior/posterior to combined depending on surgeon preference and experience. The aim of this systematic review was to review the literature on lumbosacral high-grade spondylolisthesis (HGS), identify patients at risk for progression to higher-grade slip and evaluate various surgical strategies to report on complications and radiographic and clinical outcomes.

**Methods** Systematic search of PubMed, Cochrane and Google Scholar for papers relevant to HGS was performed. 19 articles were included after title, abstract, and full-text review and grouped to analyze baseline radiographic parameters and the effect of surgical approach, instrumentation, reduction and decompression on patient radiographic and clinical outcomes.

**Results** There is a lack of high-quality studies pertaining to surgical treatment for HGS, and a majority of included papers were Level III or IV based on the JBJS Levels of Evidence Criteria.

**Conclusions** Surgical treatment for HGS can vary depending on patient age. There is strong evidence of an association between increased pelvic incidence (PI) and presence of HGS and moderately strong evidence that patients with unbalanced pelvis can benefit from correction of lumbopelvic parameters with partial reduction. Surgeons need to weigh the benefits of fixing the deformity with the risks of potential complications, assessing patient satisfaction as well as their understanding of the possible complications. However, further research is necessary to make more definitive conclusions on surgical treatment guidelines for HGS.

**Level of Evidence** II

*   High-grade spondylolisthesis
*   surgical treatment
*   instrumentation
*   Reduction
*   decompression
*   Outcome
*   comparative outcome
*   Complication

## Introduction

Spondylolisthesis refers to anterior or posterior displacement of adjacent vertebrae. The Wiltse classification divides spondylolisthesis based on anatomic presentation and etiology: isthmic, dysplastic, degenerative, traumatic, and pathological.1 Symptoms include low back pain, radicular neuropathy, or mechanical instability, and deformity as the “listhetic posture” of hyperlordosis cephald to the LS deformity, but many patients remain asymptomatic. The incidence of spondylolisthesis in the general population is 4-8%, with isthmic being the most common.2 In 1994, Bartolozzi and Marchetti developed a separate classification system that introduced “developmental spondylolisthesis,” which combined dysplastic and lytic etiology. This category highlights that many high-grade slips result from multiple stress fractures with a developmental etiology whereas lower grade slips commonly exhibit a degenerative etiology.3 Both dysplastic and isthmic components can occur simultaneously; therefore, it is difficult to deduce true slip incidence.4

Slips greater than 50% are defined as high-grade spondylolisthesis (HGS), (see Figure 1) which accounts for 1% of spondylolisthesis patients, but constitutes a more serious pathology.5 Patients who progress to HGS are frequently symptomatic with back pain, radicular symptoms from nerve root irritation and postural deformities such as compensatory lumbar hyperlordosis for focal kyphosis. Surgical intervention is generally favored over non-operative management for patients with symptomatic HGS to halt deformity progression and provide symptom relief. However, no consensus for optimal surgical modality exists. Historically, surgeries performed for HGS mimicked those utilized for low-grade spondylolisthesis such as *in situ* uninstrumented posterior fusions.1 However, due to concerns over further progression and pseudarthrosis, particularly in adults, coupled with technological and surgical advancements, surgeons now favor instrumented fusions.

![Fig. 1](http://ijssurgery.com//https://www.ijssurgery.com/content/ijss/9/50/F1.medium.gif)

[Fig. 1](http://ijssurgery.com//content/9/50/F1)

Fig. 1 
Measurement of slip angle. Meyerding scale divides the lower vertebral body into quarters and a grade of I to IV assigned respectively. Taillard grading calculates the percentage of the slip from the lower vertebra.

Current treatment options for HGS vary greatly from extent of reduction and/or instrumentation and interbody support use to anterior or posterior-based approaches with or without decompression. Existing literature on surgical approaches is limited to mostly small retrospective and uncontrolled case series, and high-quality controlled comparative series on HGS necessary for definitive conclusions are unavailable.2 This systematic review attempts to compile best available recent evidence for risk for progression, surgical approach and radiographic and clinical outcomes to formulate a comprehensive review of the safest and most effective surgical options for HGS.

## Materials and Methods

### Literature Search

We performed a systematic search of PubMed, the Cochrane Library, and Google Scholar for literature published from January 2002 - December 2014. The search was limited to human studies and articles published in English using search terms “isthmic, developmental, high-grade, and severe spondylolisthesis.” Inclusion and exclusion criteria are listed in Table 1. Articles were chosen by title, abstract and full article reviews. If studies were from the same hospital with overlapping patient populations, the most comprehensive paper was chosen and others were excluded unless they provided different results or insight for a certain question.

View this table:
[Table 1](http://ijssurgery.com//content/9/50/T1)

Table 1 
Inclusion and Exclusion Criteria

### Data Analysis

For each clinical study data on surgical approach, instrumentation type and extent, reduction procedure, and decompression procedure were extracted and analyzed based on clinical and/or radiographic outcomes. Additionally, radiographic parameters considered in the studies and used to evaluate surgical outcomes included pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), and slip angle (Figure 2).

![Fig. 2](http://ijssurgery.com//https://www.ijssurgery.com/content/ijss/9/50/F2.medium.gif)

[Fig. 2](http://ijssurgery.com//content/9/50/F2)

Fig. 2 
Left: Illustration of the spinopelvic parameters; Right: CT image of patient with HGS illustrating radiographic parameters (lumbar lordosis, pelvic tilt, sacral slope and pelvic incidence.

### Strength of Body of Literature

Each included study was rated by two independent observers for its Level of Evidence (LOE) based on the *Journal of Bone & Joint Surgery, American Volume* guidelines (Table 2).3 This literature review studied 14 clinical studies—three LOE II, five LOE III and six LOE IV—and six radiographic studies—three LOE II, one LOE III and two LOE IV. No LOE I studies on HGS treatment were found. A majority of current literature consisted of retrospective case and comparative studies.

View this table:
[Table 2](http://ijssurgery.com//content/9/50/T2)

Table 2 
Levels of Evidence for Primary Research Question.

## Clinical Recommendations and Consensus Statement

Clinical recommendations or consensus statements were made where appropriate using the GRADE/AHRQ4, 5 approach that deliberately separates the quality of evidence from the strength of recommendation or consensus statement.

## Results

### Selection of Studies

The search yielded 1,236 potentially relevant citations; of these, 1,057 were excluded based on title and/or abstract. Of the 179 articles that underwent abstract and methods review, 49 papers were extracted for full-text review. Among the final 20 papers which were chosen, two were large database studies, seven were radiographic correlation studies, and 11 were clinical surgical treatment studies (Figure 3). Three of the clinical studies were from the same group and used overlapping patient cohorts6–8. Therefore, the most pertinent and applicable data analyses were chosen for inclusion in the appropriate sections of this review. General charactersitics of the 19 papers are listed in Table 3.

![Fig. 3](http://ijssurgery.com//https://www.ijssurgery.com/content/ijss/9/50/F3.medium.gif)

[Fig. 3](http://ijssurgery.com//content/9/50/F3)

Fig. 3 
Literature review flowchart.

View this table:
[Table 3](http://ijssurgery.com//content/9/50/T3)

Table 3 
Characteristics of included studies.

## Discussion

### Radiographic Analysis and Risk of Progression

Progression of HGS is a major clinical concern for non-surgically treated patients, given the potential for pelvic remodelling and increasing complexity of surgical treatment associated with delayed management. Further, differences arise between pediatric and adult populations, and thus demand different HGS management options.

Seven LOE II studies attempted to identify patients at risk for progression to a higher-grade slip.9–14 Five studies reported a correlation between PI and slip grade,9–13 all finding that PI was significantly higher in spondylolisthesis patients compared to controls (e.g. 76° vs. 48.2-53.2°, respectively).11 Three studies did not find a difference by grade,9, 13 but one study was limited by its small population size (n = 22) and sole inclusion of patients with a previous fusion.9

No specific radiographic parameters were identified as independently associated with risk of progression. There is strong evidence of correlation between PI, age and grade of spondylolisthesis26 and between the magnitude of initial slip, slip angle and progression.9 Wang et al. also elucidated a correlation between spondylolisthesis grade, PT, LL, and exacerbated lower back pain, as measured by the ODI.38 Further, the correlation between PI and SS in adults, may explain why patients with high PI values have HGS. Despite these relationships, overall evidence suggests that PI alone is not a reliable predictor of slip progression.

Three LOE II studies and one LOE IV study addressed sacral verticality as measured by SS.12–14 Hresko et al. proposed a classification system dividing high grade spondylolisthesis cases into unbalanced and balanced pelvic groups based on the orientation, i.e. radiographic parameters, of the pelvis. Balanced pelvises had higher SS and lower pelvic tilt, whereas unbalanced pelvises incompletely compensate with lower SS and pelvic retroversion, resulting in a higher pelvic tilt (PT).12 A single retrospective study looking at patients with either unbalanced retroverted or balanced pelvises reported that spondylolisthesis grade, SS, and PT all improved significantly following partial reduction and fusion with instrumentation or casting.15 A later study by the same group found that SS increases in early grades, then decreases in Grades IV and V, possibly due to loss of contact between L5 and the cranial sacral endplate.13 An additional prospective radiographic study concluded a significant negative correlation between SS and severity of low back pain.38 Full details on included radiographic studies are available in Table 4.

View this table:
[Table 4](http://ijssurgery.com//content/9/50/T4)

Table 4 
Summary of radiographic studies.

There is good and increasing evidence in the literature that surgical treatment of HGS be based on pelvic parameters. Hresko et al. noted that increased PI with HGS is matched by specific changes in SS and PT that separates patients based on balance, with reference to an asymptomatic control group: ‘balanced’ HGS patients were similar to asymptomatic patients (lower PT, higher SS angles), while ‘unbalanced’ HGS with higher PT and lower SS were more characteristic of symptomatic patients. Hresko et al. also established a classification system for categorizing lumboscaral spondylolisthesis into low vs. high slip grade. Low slip grades are further categorized into low (<45°), normal (45-60°) or high PI (≥60°) and the high slip grades into balanced (high SS/low PT) or unbalanced (low SS/high PT).28 These findings may be related to the complex relationships and adjustment mechanisms between pelvis and global alignment.29 Lafage et al. suggest using a morphologic pelvic parameter, namely PI, and spinal parameters modifiable through surgery, such as lumbar lordosis (LL) or thoracic kyphosis (TK), to predict postoperative sagittal alignment.30

Furthermore, determining risk of progression based on radiographic parameters is complicated by the anatomical changes characteristic of HGS. S1 remodeling by dysplastic L5 and loss of L4 and S1 articulation makes border identification dificult. Vialle et al. noted that patients with low SS had a more easily reduceable spondylolisthesis14 and that SS, PT, and LL measurements in HGS were compensatory for high PI.13 Schuller *et al* found that BMI was significantly higher in a spondylolisthesis group compared to control and suggested that increased PT in HGS patients most likely results from a compensatory posterior pelvic tilt.31 The association between changes of pelvic parameters, BMI, and HGS may be related to the increasing gravitational forces seen at the lumbosacral junction associated with an increasing SS, possibly making the translational and angular components of the slip more difficult to reduce.

### Surgical Approach and Instrumentation

Four LOE III and five LOE IV studies with detailed operative descriptions7, 16–23 and two LOE II database studies addressing surgical approach were included.24, 25 Table 5 and Table 6 report the data extracted concerning surgical approaches and surgical outcomes, respectively. Surgical approaches used to treat HGS included anterior lumbar interbody fusion (ALIF), posterior/posterolateral only (PLF), transforaminal lumbar interbody fusion (TLIF) ± PLF, posterior lumbar interbody fusion (PLIF) ± PLF, and circumferential fusion. Reported outcome measures varied between authors, which include fusion status, neurologic and/or clinical deficit, patients’ perception of outcomes measured with post-operative questionanaires, and complications. Three LOE III studies directly compared circumferential fusions with interbody support to PLF-only procedures.7, 17, 20 Patients treated with circumferential fusion either had better long-term results,7, 17 or the techniques were similar in outcome.20 One LOE III study included an anterior-only cohort7 and found that anterior-only patients scored better in all SRS scores compared to PLF-only, but worse than circumferential group. This study found that overall the circumferential fusion approach resulted in significantly improved clinical, radiographic, and SRS scores post-operatively, compared to posterolateral or anterior fusions.11 A LOE IV study reported no difference in clinical and radiographic outcomes and complications between PLIF and ALIF.21 TLIF, ALIF, and PLIF were studied in the included articles, however none of the considered studies directly compared the three procedures.7, 16, 17, 19, 21–23

View this table:
[Table 5](http://ijssurgery.com//content/9/50/T5)

Table 5 
Summary of Surgical Strategy

View this table:
[Table 6](http://ijssurgery.com//content/9/50/T6)

Table 6 
Surgical Outcome, Complications and Clinical Recommendations Per Author.

Although no definitive recommendations can be established, literature suggests that circumferential fusion with interbody support has lower incidence of pseudarthrosis and possibly better chance of longterm clinical success compared to those treated with posterior only techniques in the absense of interbody support. Despite this finding, relative to additional interbody support from a posterior-based approach (TLIF and PLIF), combined anterior/posterior approaches are associated with longer hospital stays and increased blood loss and surgical time,32, 33 which can be associated with greater risk of complications.34 DeWald et al. reviewed adult HGS patients and recommended *in situ* posterior fusion with instrumentation from L4 to S1 with consideration for partial reduction and vertebrectomy. Helenius et al. retrospectively studied the pediatric population undergoing posterolateral, anterior and circumferential fusion *in situ* without instrumentation and found that the circumferential group had the best health-related-quality-of-life scores and lowest percentage of lumbosacral kyphosis progression. No similar adult studies were found. Nonetheless, well-designed prospective studies that directly compare different fusion modalities are necessary to provide better evidence on comparative treatment effectiveness.

Surgical management of HGS involves various techniques such as instrumentations, reductions, and decompressions. Instrumentation plays a more significant role in adults than children as uninstrumented *in situ* circumferential fusion is considered more viable in treating pediatric HGS.6, 8, 17 With regards to the extent of construct, instrumentation to the L4-5 level provides better stability and more vertical fusion as opposed to the more horizontal fusion that occurs with L5-sacrum fusion.35 Some surgeons extend instrumentation to the ilium due to high failure rates at the lumbosacral juction with long posterior instrumentation ending at S1,36 but its value for HGS patients remains questionable.16, 20

Innovative technology such as the Luque box and the Jackson intrasacral rod have shown improved fusion and clinical outcomes but have also resulted in higher complication rates attributed to the instrumentation itself.22 Although technological advancement is paramount to providing patients with the best possible care, the importance of properly evaluating novel spinal instrumentation is equally critical prior to routine clinical acceptance. Two LOE III studies discussed uninstrumented fusion in children.8, 17 Poussa et al. showed that compared to those treated with reduction and instrumented fusion with transpedicular fixation, adolescents who were fused *in situ* circumferentially without instrumentation had better ODI and SRS scores despite having evidence of asymptomatic nerve root impingement on MRI and no reduction of their slip grade.8 Molinari et al. attempted uninstrumented *in situ* PLF in 11 pediatric patients and reported a 45% pseudarthrosis rate (n = 5)17 with pain and increased deformity requiring reoperations. These patients underwent circumferential fusions with instrumentation and ultimately achieved solid fusion.

Various pedicle screw constructs, extending from L3, L4, or L5 to S1 with or without iliac fixation, and transsacral screws were used for HGS procedures. The most common instrumentation for adults were L4-S1 pedicle screws.8, 16, 20, 21, 23 For children, reduced circumferential monosegmental L5-S1 instrumentation and circumferential *in situ* fusion from L4/L5 to S1 without instrumentation yielded the best results with no neurological complications and improvement of slip angle.18 One LOE III study found similar complication rates and surgical outcomes in unilateral TLIF's and transvertebral screw fixations of the lumbosacral spine.20 Two LOE IV studies reported a subcohort receiving instrumentation to the ilium without report on results,16 and one study, without reference to evidence, recommended extension to the ilium in adult patients, particularly for revisions and unstable spondylolisthesis.23

A LOE IV study investigating two constructs, a Luque box and a Jackson intrasacral rod extending from L4 to sacrum, reported that all patients achieved solid fusion with an overall 19% reoperation rate and a 23% incidence of transient neurological deficits.22 One LOE IV study investigating the “double-plate” technique found that it caused implant-related complications in 22% of patients, late infections in 12%, and postoperative neurological complications in 30%, despite achieving optimal deformity reduction and high fusion rates.19

Nine clinical studies reported on decompression but none directly-examined it as an independent variable. Gill decompression, involving the removal of L5 lamina and fibrocartilaginous tissue at the pars, was most commonly performed. Poussa et al. reported better outcomes in reduction with decompression than in *in situ* fusion with no decompression (decompression is not concurrently performed with *in situ* fusions).8 This difference could not be attributed to decompression alone, given the group disparity and the multiple factors being compared.

### Reduction of Slip Angle/Grade

Two LOE III studies compared reduced and nonreduced cohorts.8, 17 Poussa et al. found that the adolescent *in situ* group had better ODI and SRS scores than the reduced cohort.8 Further, this group found that patients treated with partial reduction had better clinical outcomes—mean ODI was 7.2 in partial reduction vs. 1.6 in *in situ* group and SRS score 90.0 vs. 103.9.12 Molinari et al. revealed increased pseudarthrosis and deformity progression in *in situ* PLF group compared to the reduced PLF group (45% vs. 29%, 36% vs. 29%, respectively).17 Dewald et al. was the only study addressing *in situ* fusion and reduction in adults, but there was not enough evidence to reach definitive conclusions.23 One LOE III and one LOE IV study reported cases of attempts to reduce slip angle by operative positioning without attempting to change slip grade.20, 21 Both studies reported slip angle improvements of 10-15° without significant slip grade change, safe and effective surgical results with stable arthrodesis rate, no long-term neurologic deficits, and improvements in gait disturbance. 20, 21 No studies directly compared partial and complete reduction. Three LOE III and two LOE IV studies reported on partial slip reduction techniques, either via temporary distraction or direction reduction. 8, 16–18, 23 Two studies incorporated decompression and partial reduction techniques and highlighted that *in situ* may be associated with improved outcomes in children and adolescents but only with anterior support. This observation is due to concerns about increased incidence of pseudarthrosis and deformity progression without anterior support. 8, 17 One LOE IV study attempted complete reduction in all patients and achieved full reduction in 95% of patients. 19 However, they reported poor outcomes overall and a high incidence of neurological and infectious complications. Another study reported complete reduction only in two patients who had abnormally mobile olistheses, but no separate sub-cohort results were reported.23

The extent of reduction and its clinical relevancy and safety are controversial, as reports of associated neurologic complication rates in the literature are mixed. Molinari et al. reported positive outcomes in a circumferential partial reduction cohort, but results were not significantly different from the *in situ* cohort, implying that reduction was not the most important contributor to positive outcome.17 Poussa et al. stated that *in situ* circumferential fusion is preferable for pediatric patients over reduction. However, partial reduction allows sagittal malalignment correction and would theoretically create a more favorable environment for fusion by increasing contact surface area between two vertebrae and thus increasing osteogenic, osteoinductive and osteoconductive effects. Studies indicate successful clinical outcome with slip angle reduction without an increased risk for neurological complications, but definitive comparative data on slip angle reduction without surgical reduction is lacking.19, 20

### Post-Operative Management

Only one of the twenty studies reported on post operative management of in situ fusions.17 Patients were immobilized for 4 to 7 months in a hyperextension cast incorporating both thighs. In comparison, patients treated with instrumentation had 4 months of immobilization after surgery that consisted of bed rest. In addition to bed rest, some patients also wore a cast or a brace.

## Conclusion/Limitations

This systematic review presents potential risk factors for slip progression and radiographic and clinical outcomes based on different types of surgical procedure. There is strong evidence that treatment of HGS should be influenced based on pelvic parameters, i.e. sacral slope and pelvit tilt that determine pelvic balance. Unfortunately, prospective, randomized and controlled studies providing a more reliable conclusion on surgical treatment strategies for HGS have not been conducted to date. Surgeons must weigh fixing the deformity with avoiding complications, assessing patient satisfaction and patients’ understanding of possible complications.

### Evidence Summary

Overall strength of effectiveness of various surgical procedures for HGS is “low,” meaning there is low confidence that the evidence reflects true effect and further research is likely to change the confidence in the estimate of effect.37 The overall strength of appropriateness of reduction and instrumentation in addition to fusion for HGS is “low,” but “insufficient” for decompression, meaning that evidence is either unavailable or does not permit a conclusion. The overall strength of correlation between higher PI and progression is “high.” For adults, this review recommends that instrumented circumferential fusion provides the most promising clinical and radiographic outcome compared to anterior-only fusion and PLF in adults. For children and adolescents, this review recommends *in situ* fusion along with thorough long-term follow-up to check for deformity and quality of life. Full details are available in Table 7.

View this table:
[Table 7](http://ijssurgery.com//content/9/50/T7)

Table 7 
Strength of Evidence.

## Disclosures

Virginie LaFage owns stock in Nemaris Inc and is on its Board of Directors; has speaking and/or teaching arrangements with MSD, DePuy, and Medicrea; and has received grants from DePuy, ISSG, SRS, and the NIH. The other authors report no disclosures.

*   Copyright © 2015 ISASS - This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery

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