Radiographic Risk Factors for Adjacent Segment Disease Following Anterior Cervical Discectomy and Fusion (ACDF): A Systematic Review and Meta-Analysis

Abstract

Study Design

Systematic review and meta-analysis.

Objectives

To assess the radiographic risk factors for adjacent segment disease (ASD) following anterior cervical discectomy and fusion (ACDF) for degenerative cervical spine pathologies.

Methods

PubMed, Embase and the Cochrane Library databases were searched up to December 2023. The primary inclusion criteria were degenerative spinal conditions treated with ACDF, comparing radiological parameters in patients with and without postoperative ASD. The radiographic parameters included intervertebral disc height, cervical sagittal alignment, sagittal segmental alignment, range of motion, segmental height, T1 slope, sagittal vertical axis (SVA), thoracic inlet angle (TIA), and plate to disc distance (PPD). Risk of bias was assessed for all studies. The Cochrane Review Manager was utilized to perform the meta-analysis.

Results

From 7044 articles, 13 retrospective studies were included in the final analysis. Three studies had “not serious” bias and the other 10 studies had serious or very serious bias. The total number of patients in the included studies was 1799 patients. Five studies included single-level ACDF, 2 studies included multi-level ACDF, and 6 studies included single or multi-level ACDF. On meta-analysis, the significant risk factors associated with ASD development were reduced postoperative cervical lordosis (mean difference [MD] = 3.35°, P = .002), reduced last-follow-up cervical lordosis (MD = −3.02°, P = .0003), increased preoperative to postoperative cervical sagittal alignment change (MD = −3.68°, P = .03), and the presence of developmental cervical canal stenosis (Odds ratio [OR] = 4.17, P < .001).

Conclusions

Decreased postoperative cervical lordosis, greater change in cervical sagittal alignment and developmental cervical canal stenosis were associated with an increased risk of ASD following ACDF.

Keywords

anterior cervical discectomy and fusion adjacent segment disease radiographic parameters risk factors sagittal alignment canal stenosis

Introduction

Anterior cervical discectomy and fusion (ACDF) is a frequent surgical procedure for cervical spine degenerative conditions, with more than 130,000 ACDFs performed yearly in the United States and an annual increase of more than 5%.^1-4

Despite its effectiveness in relieving neck pain, radiculopathy, and myelopathy, ACDF is not without short-term and long-term complications.⁵ Following ACDF, there is alteration in the cervical spine biomechanics with increased intradiscal pressure and segmental motion at adjacent segments.^6,7 These changes contribute to the development of radiographic degenerative changes in the adjacent levels.^8,9 Yet, radiographically evident degenerative changes do not necessarily lead to increased symptomatic disease incidence.¹⁰ Adjacent segment disease (ASD) comprises a clinically significant degeneration of the level above or below the fusion area with symptoms of new radiculopathy and/or myelopathy, which may lead to severe dysfunction and the need for reoperation.^11,12

The incidence of ASD has been reported in the literature, ranging from 2.9% to 92%, with approximately 40% reoperations after spine surgery.^13-15 Notably, these revision surgeries are associated with enormous direct and indirect medical costs.¹⁶

Given this high prevalence and the potential detrimental effects, identification of the pre and perioperative factors linked to ASD could have significant clinical and economic implications.^17,18

The risk factors of ASD are still not fully understood, and the findings of different studies have been inconsistent.¹⁹ Up to now, radiographic risk factors for ASD development after ACDF have not been extensively analyzed. Therefore, this systematic review and meta-analysis aimed to identify the radiographic risk factors for ASD occurrence following the management of degenerative cervical spine pathologies with ACDF.

Methods

This systematic review was performed while adhering to the PRISMA statement guidelines.²⁰

Electronic literature search

PubMed, Embase and the Cochrane Library databases were searched for relevant articles from the commencement to December 2023.

The search terminology included anterior cervical discectomy and fusion or ACDF AND adjacent segment degeneration, adjacent segment disease, adjacent segment failure, proximal junctional failure, proximal junctional disease, distal junctional failure, distal junctional disease, reoperation spine fusion, or extension of fusion.

Studies Selection

Three independent reviewers (Z.B., M.B. and C.Y.) screened the studies for qualification of full-text review. Each article title and abstract were reviewed, and articles that were not relevant to the topic of the study were excluded. Rayyan.ai²¹ was used to facilitate the screening and selection process. Full-text evaluation was then performed to choose the studies that matched the criteria for inclusion.

Inclusion and Exclusion Criteria

Inclusion criteria were: (A) Studies that included degenerative spinal conditions requiring ACDF. (B) Articles that compared the radiological parameters in patients with and without postoperative ASD. (C) English articles with available full text. (D) Each comparative group must have at least ten patients.

Exclusion criteria were: (A) Patient with congenital diseases, trauma or infection, scoliosis, or tumors. (B) Articles that reported clinical risk factors only. (C) Articles that included other procedures such as disc arthroplasty and posterior fusion (D) Studies that only reported the incidence or treatment of ASD without risk factors. (E) Non-clinical or animal studies, reviews, or abstracts, Table 1.

Table 1.

PICO Table.

Study Component	Inclusions	Exclusions
Participants	Degenerative cervical spinal conditions requiring surgery	Congenital or traumatic pathologies, infection, or malignancy, primary diagnosis of scoliosis
Intervention	Anterior cervical discectomy and fusion (ACDF)	• Other cervical spine surgeries
Intervention	Anterior cervical discectomy and fusion (ACDF)	• Lumbar and thoracolumbar surgeries
Comparators	Patients with and without postoperative adjacent segment disease (ASD)	• ASD vs subclinical ASD
Comparators		• Early ASD vs late ASD
Outcomes	Radiological risk factors for ASD	• Clinical risk factors
Outcomes	Radiological risk factors for ASD	• Treating ASD without reporting risk factors
Study design	• Prospective	• Non-clinical studies or animal studies
	• Retrospective	• Narrative reviews
	• Randomized controlled trials	• Systematic reviews and meta-analysis
		• Abstracts, editorials, letters, posters, or erratum
		• Case reports
		• Biomechanical studies
		• Comparative studies with less than ten patients per treatment group
Publication	• Full text • English language	• Duplicate publications of the same study without reporting on different outcomes
Publication		• Articles identified as preliminary reports when results are published in later versions
Timing	From inception to Dec 2023

Any disagreement between the reviewers over the inclusion of the studies was resolved by a discussion.

Data Extraction

The following information was obtained and written in a custom-made sheet using Microsoft Office Excel® version 2022 (Microsoft Corporation, Redmond, Washington, United States): authors, study design, demographics, follow-up duration, surgery, number of levels, ASD diagnostic methods and definition, values of each radiographic risk factor for both ASD and No-ASD groups, odds ratio, and P-value. Two reviewers (M.B. and C.Y.) independently extracted data from each study.

Quality Assessment

Two reviewers (M.B. and C.Y) independently evaluated the risk of bias in the included observational studies based on the methodological index for non‐randomized studies (MINORS) checklist.²² A MINORS score of 17-24 indicated “not serious” bias. A score of 10-16 indicated “serious” bias. A score of 9 or lower indicated “very serious” bias. In a case of a disagreement, the senior reviewer (ZB) reviewed and resolved the points in question.

Outcome Measures

The primary outcome measure was the radiographic risk factors for ASD development after cervical spinal surgeries. The radiographic parameters included intervertebral disc height, cervical sagittal alignment, sagittal segmental alignment, range of motion, segmental height, T1 slope, sagittal vertical axis (SVA), thoracic inlet angle (TIA), and plate-to-disc distance.

statistical Analysis

The Cochrane Review Manager (RevMan V.5), Nordic Cochrane Centre, Copenhagen, Denmark, was Utilized to Perform the Meta-analysis.

Meta-analysis of a specific risk factor was performed if at least two studies reported the value of that risk factor in patients with and without ASD.

In continuous data, the mean difference (MD) and 95% confidence interval (CI) were estimated, whereas the odds ratio (OR) and 95% CI were calculated in dichotomous data.

The statistical heterogeneity was judged using the I² test. The fixed-effects model was used with I² values <50%, while the random-effects model was used with I² values >50%. P-values less than .05 were significant.

Results

Search Results and Study Selection

Database searches and removal of duplicates yielded 7044 unique articles.After the screening of titles and abstracts, 85 studies were selected for full-paper review. Eventually, 13 articles^23-35 were considered in the qualitative and quantitative analyses, Figure 1.

Figure 1.

The PRISMA flow diagram.

Risk of Bias and Methodological Quality

All articles^23-35 were non-randomized and were evaluated using MINORS criteria. Three^24,31,35 had “not serious” bias. Seven^27-30,32-34 were found to have “serious” bias. Very serious bias was found in 3 studies,^23,25,26 Table 2.

Table 2.

Methodologic Quality Assessment of the Included Non-randomized Studies Utilizing the Methodological Index for non‐randomized Studies (MINORS) Criteria.

No.	Studies	Methodological Items												Score	Bias
No.	Studies	1	2	3	4	5	6	7	8	9	10	11	12	Score	Bias
1	Abudouaini 2021	2	1	1	2	0	2	1	0					9/16	Very serious
2	Ahn 2016	2	2	2	2	0	2	2	0	2	2	1	2	19/24	Not serious
3	Faldini 2011	2	1	1	2	0	2	1	0					9/16	Very serious
4	Ishihara 2004	2	2	0	2	0	2	1	0					9/16	Very serious
5	Li 2015	2	2	1	2	2	2	2	0					13/16	Serious
6	Louie 2017	2	2	1	2	0	2	2	0					11/16	Serious
7	Rudisill 2022	2	2	1	2	0	2	1	0					10/16	Serious
8	Teo 2021	2	2	2	2	0	2	2	0					12/16	Serious
9	Wang 2017	1	2	1	2	0	2	2	0	2	2	1	2	17/24	Not serious
10	Wei 2023	2	2	1	2	0	2	2	0					11/16	Serious
11	Wong 2021	2	2	1	2	0	2	2	0					11/16	Serious
12	Yu 2016	0	1	1	2	0	2	2	0	2	2	1	2	15/24	Serious
13	Zhao 2014	1	2	2	2	0	2	1	0	2	2	2	2	18/24	Not serious

Item 1: Clearly stated aim.

Item 2: Inclusion of consecutive patients.

Item 3: Prospective data collection.

Item 4: Endpoints appropriate to study aim.

Item 5: Unbiased assessment of study endpoint.

Item 6: Follow-up appropriate to study aim.

Item 7: Loss to follow-up <5%.

Item 8: Prospective calculation of study size.

Additional criteria in the case of comparative study

Item 9: An adequate control group.

Item 10: Contemporary groups.

Item 11: Baseline equivalence of groups.

Item 12: Adequate statistical analyses.

Characteristics of Included Studies

All studies^23-35 were retrospective. The total number of patients in the included studies was 1788 patients with degenerative cervical spine conditions who had ACDF. Overall, 1034 (57.83%) patients were males, and 754 (42.17%) were females.

In terms of the number of operated levels, 5 studies^23-25,27,31 included single-level ACDF, 6 studies^{26,28,29,32,34,35} included single or multi-level ACDF, and 2 studies^30,33 included multiple-level ACDF.

Detailed characteristics of the included studies are presented in Table 3.

Table 3.

Characteristics of the Included Studies.

No.	Author/Year, Study Design MINORS Score	Demographics (Mean or %)	Spine Pathology Diagnosis	Operation	No. of Operated Levels	ASD Diagnostic Tools	ASD Diagnostic Criteria
1	Abudouaini 2021- Retrospective- MINORS score: 9/16	N: 138Age: 48.03 ± 9.51 yFemales: 63 (45.65%)Males: 75 (54.35%)N ASD/No-ASD- Superior levelGroup a (ISH change <2 mm): 5 (11.90%)/37 (88.10%)Group B (ISH change 2-4 mm): 4 (5.88%)/64 (94.12%)Group C (ISH change >4 mm): 4 (14.29%)/24 (85.71%)- Inferior levelGroup A: 7 (16.67%)/35 (83.33%)Group B: 5 (7.35%)/63 (92.65%)Group C: 3 (10.71%)/25 (89.29%)F/U: 22.83 ± 6.272 mo	Symptomatic CDDD with spondylotic radiculopathy Or myelopathy	ACDF	Single	Radiological (standing lateral, flexion and extension X-rays)	• New or enlarged OALL• >30% new or increased disc space narrowing• New or enlarging osteophytes• Endplate sclerosis
2	Ahn 2016	N: 64	CDDD	ACDF	Single	Radiological (radiography, CT, MRI)	• Disc signal change
	- Retrospective	Age: 50.91 ± 3.79 y (ASD); 48.72 ± 3.9 y (No-ASD)					• Disc herniation
	- MINORS score: 19/24	Females: zero (0%)					• Anterior/posterior longitudinal ligament calcification
		Males: 64 (100%) N ASD/No-ASD: 32 (50%)/32 (50%) F/U: 37.78 ± 1.41 mo (ASD); 38.50 ± 1.83 mo (No-ASD)					• Osteophytes formation
							• ≥25% decrease in disc height
3	Faldini 2011- Retrospective- MINORS score: 9/16	N: 107Age: 46 ± 7 yFemales: 14 (13.08%)Males: 93 (86.92%)N ASD/No-ASD: 43 (40%)/64 (60%)F/U: 192 mo	CDDD	ACDF	Single	Radiological (X-rays)	• Osteophytes formation• Periarticular ossicles• Cartilage narrowing• Subchondral bone sclerosis• Pseudocysts formation• Altered bone shape
4	Ishihara 2004- Retrospective- MINORS score: 9/16	N: 112Age: 51Females: 38 (33.93%)Males: 74 (66.07%)N ASD/No-ASD: 19 (17%)/93 (83%)F/U: 112.8 mo	Intervertebral disc HNP and cervical spondylosis	ACDF	Single or multiple	Clinical radiological (MRI or myelography)	ClinicalNew radiculopathy or myelopathy symptomsRadiologicalCompressive lesion at an adjacent level
5	Li 2015- Retrospective- MINORS score: 13/16	N: 116Age: Mean: 50.2 ± 9.7 yFemales: 55 (47.41%)Males: 61 (52.59%)N ASD/No-ASD: 28 (24.1%)/108 (93.1%) F/U: 30.6 mo (ASD); 31.2 mo (No-ASD)	Cervical disc HNP with radiculopathy	ACDF	Single	Radiological (static and dynamic lateral X-rays)	• Anterior longitudinal ligament calcification• Narrowing of disc space with or without posterior osteophytes• New anterior or enlarging osteophyte
6	Louie 2017- Retrospective- MINORS score: 11/16	N: 83Age: 50.5 ± 10.7 yFemales: 38 (46%)Males: 45 (54%)N ASD/No-ASD: 30 (36.1%)/53 (63.9%) F/U: 29.2 ± 20.3 mo	Cervical radiculopathy, myelopathy, or myelo- radiculopathy	ACDF	Single or multiple	Clinical radiological (X-rays)	ClinicalNew radicular or myelopathy symptoms indicative of pathology at C7-T1Radiological• >50%disc space narrowing• New or enlarged osteophytes• End plate sclerosis• Increased calcification of the anterior longitudinal ligament) + indicative of pathology at C7-T1)
7	Rudisill 2022- Retrospective- MINORS score: 10/16	N: 366Age: 51.4 ± 11.1 yFemales: 180 (49.2%)Males: 186 (50.8%)N ASD/No-ASD: 97 (26.5%)/269 (73.5%)F/u: 18.7 ± 20.9 mo	Disc degeneration, disc herniation, spondylosis or spondylolisthesis causing myelopathic or radicular symptoms	ACDF	Single or multiple	Radiological (X-rays, MRI)	• New/enlarged anterior osteophytes (bony outgrowth>2 mm in the anterior or posterior edges of adjacent vertebral bodies)
							• New/increased calcification of the anterior longitudinal ligament
							• 30% new/increased disc space narrowing
							• >2 mm new spondylolisthesis
							• New endplate sclerosis at adjacent levels
							• New endplate sclerosis at adjacent levels
8	Teo 2021	N: 46	CDDD	ACDF	3 levels	Radiological (lateral X-rays)	• Disc space narrowing
	- Retrospective	Age: 59.7 y					• New posterior osteophytes
	- MINORS score: 12/16	Females: 23 (50%)
	- MINORS score: 12/16	Males: 23 (50%) N ASD/No-ASD: 27 (58.7%)/19 (41.3%) F/U: 60.4 mo
9	Wang 2017	N: 144	Cervical radiculopathy and myelopathy	ACDF	Single	Clinical Radiological (X-rays, CT)	Clinical
9	- Retrospective- MINORS score: 17/24	Age: 48.3 yFemales: 69 (47.92%)Males: 75 (52.08%)N ASD/No-ASD: 36 (25%)/108 (75%)F/U: 88.8 mo	Cervical radiculopathy and myelopathy	ACDF	Single	Clinical Radiological (X-rays, CT)	New myelopathic or radiculopathic symptomsRadiologicalDegenerative change adjacent to the fusion level
10	Wei 2023	N: 219	Cervical spondylosis	ACDF	Single or multiple	Clinical Radiological (X-rays)	Clinical
10	- Retrospective- MINORS score: 11/16	Age: 55.72 ± 11.51 yFemales: 88 (40.18%)Males: 131 (59.82%)N ASD/No-ASD: 46 (21%)/173 (79%)F/U: ≥ 5 y	Cervical spondylosis	ACDF	Single or multiple	Clinical Radiological (X-rays)	Cervical pain, cervical spondylotic radiculopathy or cervical spondylotic myelopathyRadiological• Cervical disc degeneration• Cervical instability• Local kyphosis• Local bone graft nonfusion
11	Wong 2021- Retrospective- MINORS score: 11/16	N: 62Age: 52.4 ± 10.9 yFemales: 34 (54.8%)Males: 28 (45.2%)N ASD/No-ASD: 32 (51.6%)/30 (49.4%)F/U: ≥ 6 mo	Degenerative cervical spine pathology	ACDF	Multiple	Radiological (lateral X-rays)	• New/enlarged anterior osteophytes• New/increased anterior longitudinal ligament calcification• 30% new/increased disc space narrowing• >2 mm spondylolisthesis• New endplate sclerosis at adjacent levels
12	Yu 2016- Retrospective- MINORS score: 15/24	N: 263Age: 50.35 ± 6.91 yFemales: 122 (46.29%)Males:141 (53.61%)N ASD/No-ASD: 138 (52.47%)/125 (47.53%)<F/U: 67.53 ± 10.52 mo	Cervical disc HNP or cervical spondylosis	ACDF	Single or multiple	Radiological (lateral X-rays, MRI)	• Kellgren degeneration grading ≥ grade 2• Miyazaki intervertebral disc degeneration grading ≥3 grade III
13	Zhao 2014	N: 68	Myelopathy, radiculopathy, or myeloradiculopathy	ACDF	Single or multiple	Radiological (lateral X-rays, MRI)	Miyazaki’s grading system for cervical disc degeneration
	- Retrospective	Age: 54 y
	- MINORS score: 18/24	Females: 30 (44.12%)
		Males: 38 (55.88%)
		N ASD/No-ASD: 34 (50%)/34 (50%) F/U: ≥18 mo

Abbreviations: ISH, Intervertebral space height; CDDD, cervical disc degenerative disease; OALL, ossification of the anterior longitudinal ligament; ACDF, anterior cervical discectomy and fusion; HNP, herniated nucleus pulposus.

Meta-Analysis of Radiographic Risk Factors

Cervical Sagittal Alignment

Six studies^{24,26,27,29,30,33} were included in the meta-analysis of the preoperative cervical sagittal alignment, which was not different in ASD and No-ASD groups (mean difference [MD] = -.13°; 95% confidence interval [CI] = −1.29 to 1.04; P = .83; I² = 18%).

However, patients with ASD had significantly lower postoperative cervical lordosis than patients without ASD (MD = −3.35°; 95% CI = −5.43 to −1.27; P = .002; I² = 0%) on the meta-analysis performed on two studies.^27,30

Similarly, patients with ASD had a significantly lower cervical lordosis at the last follow-up time than patients without ASD (MD = −3.02°; 95% CI = −4.65 to −1.40; P = .0003; I² = 0%).

On meta-analysis from two studies,^28,30 the preoperative to postoperative cervical sagittal alignment change was significantly higher in patients with ASD than in patients with no ASD (MD = 3.68°; 95% CI = .34 to 7.03; P = .03; I² = 0%), while the postoperative to last follow-up cervical sagittal alignment change was insignificantly lower in patients with ASD than patients without ASD (MD = −2.05°; 95% CI = −4.25 to .15; P = .07; I² = 40%), Figure 2.

Figure 2.

Forest plots of meta-analysis of cervical spine sagittal alignment.

Sagittal Segmental Alignment

Five studies^{24,26,27,29,33} were included in the meta-analysis of the preoperative sagittal segmental alignment, which was found to be comparable in patients with and without ASD (MD = .16°; 95% CI = −.55 to .87; P = .66; I² = 38%).

Two studies^27,30 evaluated the postoperative and last follow-up sagittal segmental alignment. Both postoperative and last follow-up sagittal segmental alignment were lower in patients with ASD than patients without ASD with no statistical significance (MD = −1.07°; 95% CI = −2.44 to .29; P = .12; I² = 0%) (MD = −1.06°; 95% CI = −2.30 to .17; P = .09; I² = 7%), respectively, Figure 3

Figure 3.

Forest plots of meta-analysis of the sagittal segmental alignment.

Upper and lower segmental range of motion

Meta-analysis of the preoperative upper and lower segmental range of motion was feasible in two studies.^24,26

The preoperative upper segmental range of motion was comparable in patients with and without ASD (MD = .25°; 95% CI = −1.05 to 1.55; P = .70; I² = 0%). The preoperative lower segmental range of motion was higher in patients with ASD (MD = 1.95°; 95% CI = .01 to 3.89; P = .05; I² = 58%), Figure 4.

Figure 4.

Forest plots of meta-analysis of the preoperative upper and lower segmental range of motion.

T1 Slope

On meta-analysis from two studies,^29,30 the preoperative T1 slope was comparable in patients with and without ASD (MD = .45°; 95% CI = −1.06 to 1.95; P = .56; I² = 0%).

With pooled data from two studies,^28,30 the preoperative to postoperative T1 slope change was higher in patients with ASD but without statistical significance (MD = 1.03°; 95% CI = −3.11 to 5.18; P = .63; I² = 55%). Additionally, the postoperative to last follow-up T1 slope change was lower in patients with ASD without statistical significance (MD = −1.62°; 95% CI = −3.61 to .37; P = .11; I² = 0%), Figure 5.

Figure 5.

Forest plots of meta-analysis of T1 slope.

Sagittal Vertical Axis

On meta-analysis from two studies,^29,30 the preoperative sagittal vertical axis was non-significantly higher in patients with ASD than patients without ASD (MD = 2.50 mm; 95% CI = −7.67 to 12.66; P = .63; I² = 85%).

With pooled data from two studies,^28,30 both preoperative to postoperative and postoperative to last follow-up sagittal vertical axis changes were lower in patients with ASD than in patients without ASD with no statistical significance (MD = −1.03 mm; 95% CI = −4.55 to 2.48; P = .56; I² = 0%) and (MD = −.37 mm; 95% CI = −3.21 to 2.48; P = .80; I² = 0%), respectively, Figure 6.

Figure 6.

Forest plots of meta-analysis of sagittal vertical axis.

Proximal and Distal Adjacent Segment Lordosis

Two studies^29,33 were included in the meta-analysis of the preoperative proximal and distal adjacent segment lordosis, which was found to be comparable in patients with and without ASD (MD = .77°; 95% CI = −.99 to 2.53; P = .39; I² = 0%) and (MD = .61°; 95% CI = −1.95 to 3.17; P = .64; I² = 69%), respectively, Figure 7.

Figure 7.

Forest plots of meta-analysis of the preoperative proximal and distal adjacent segment lordosis.

Upper and lower segmental disc height

Two studies^24,34 were included in the meta-analysis of the preoperative upper and lower adjacent segmental disc height, which was to be comparable in patients with and without ASD (MD = −.09 mm; 95% CI = −.31 to .14; P = .45; I² = 3%) and (MD = −.04 mm; 95% CI = −.24 to .17; P = .73; I² = 39%), respectively.

Developmental Cervical Canal Stenosis

Pooled data from two studies^31,35 showed that a diagnosis of developmental cervical canal stenosis significantly increases the odds of ASD development (OR = 4.17; 95% CI = 2.08 to 8.38; P < .001; I² = 39%), Figure 8.

Figure 8.

Forest plots of meta-analysis of preoperative adjacent segmental disc height and developmental cervical canal stenosis.

Other Risk Factors

Some studies reported significant radiographic risk factors for ASD, but meta-analysis was not feasible given that each risk factor was reported in a single study or were reported in incomplete values. Those significant risk factors included preoperative, postoperative, and last follow-up intervertebral disc height in addition to the preoperative to postoperative change,²⁷ postoperative kyphotic sagittal segmental alignment,²⁵ preoperative to last follow-up increase in the upper segmental range of motion,²⁴ preoperative to last follow-up change in the upper segmental disc height,²⁴ decreased preoperative and postoperative TIA,³² decreased postoperative arc chord distance,³⁴ preoperative increased T1 slope minus cervical lordosis,³⁰ indentation of dura matter in preoperative myelography,²⁶ disc protrusion in preoperative MRI,²⁶ plate to disc distance (PDD),³⁴ disc bulge impingements in preoperative MRI ,³⁵ and increased asymmetry of preoperative total cross-sectional area (CSA) of deep neck paraspinal muscles at C3, C5, C6, and C7 levels,³³ Table 4.

Table 4.

Summary of ASD Incidence With Various Radiological Parameters.

Discussion

ACDF is an effective procedure for addressing degenerative diseases of the cervical spine; however, some patients may develop ASD due to the increased stress on the levels above or below the fused segments.^11,36,37 This may lead to a progressive worsening of symptoms with a possible need for revision surgery.^36,38

This systematic review and meta-analysis focused on investigating the radiographic parameters as possible risk factors for ASD development following ACDF. Overall, the significant risk factors included lower postoperative and last follow-up cervical lordosis, higher preoperative to postoperative cervical spine sagittal alignment change, and the presence of developmental cervical canal stenosis.

Li et al²⁷ compared the preoperative and follow-up cervical sagittal alignment of patients with degenerative changes and straightening or kyphosis of the cervical spine who underwent an ACDF and found that the surgery was effective in correcting the cervical sagittal misalignment. However, the ASD group maintained a smaller sagittal alignment angle.²⁷ Teo et al³⁰ found that both ASD and non-ASD groups had a gradual decrease in mean cervical sagittal alignment over the course of postoperative follow-ups. However, there was a more significant deterioration in patients who developed ASD.³⁰ In addition, upon analyzing radiographs from the study, it was observed that an increase in cervical kyphosis often led to the development of ASD.³⁰ Their findings corroborate the hypothesis that sagittal imbalance after a cervical fusion abnormally distributes stress and predisposes the adjacent segment to an increased rate of degeneration.¹¹ Similarly, in a biomechanical study using cadaveric specimens, Patwardhan et al³⁹ concluded that cervical sagittal imbalance exacerbates the mechanical load and degeneration on the levels adjacent to cervical multilevel fusions.

Two studies^28,30 reported that change of cervical sagittal alignment between preoperative and postoperative was significantly higher in patients with ASD in comparison to patients without ASD. Louie et al²⁸ found that patients who required a greater correction in cervical sagittal alignment had an increased risk of radiographic ASD, likely due to a greater change in the distribution of stress.

Ahn et al.²⁴ and Ishihara et al²⁶ reported that the preoperative range of motion at the upper adjacent level was not different between the ASD and No-ASD groups. Yet, a meta-analysis of the two studies^24,26 found that preoperative lower segmental range of motion was higher in patients with ASD. This finding needs to be further investigated in future meta-analysis studies, including more studies, given that the P-value was exactly .05.

Congenital cervical canal stenosis impacts the cervical kinematics with increased mechanical loading, and degenerative disc disease may be associated with a cervical spinal canal diameter of less than 13 mm.⁴⁰

Current meta-analysis revealed that a diagnosis of developmental cervical canal stenosis significantly increased the chances of developing ASD. Wang et al³¹ and Zhao et al³⁵ found that developmental cervical canal stenosis was a significant risk factor for ASD following ACDF. Morishita et al⁴⁰ reported that congenital stenosis impacts cervical kinematics with increased mechanical loading, and that degenerative disc disease may be associated with a cervical spinal canal diameter of less than 13 mm. Zhang et al⁴¹ concluded that congenital stenosis is a predictor of radiographic ASD following ACDF.

Several significant radiographic risk factors for ASD were identified, for which a meta-analysis could not be conducted. However, the association between these factors and ASD development is still uncertain and future studies are needed to investigate the interplay between these factors and the risk of ASD. For example, Yu et al³⁴ reported that a PDD of <5 mm was a significant risk factor for ASD. The use of longer plates in ACDF reduces the PPD, which may increase cervical spine stiffness during motion and exert undue stress on the adjacent segments.³⁴

Wei et al³² reported that decreased preoperative and postoperative TIA was a risk factor for ASD. The TIA is an important parameter of the cervical spine sagittal balance since the upper endplate of the T1 vertebra forms the base of the cervical spine.⁴²

Wong et al³³ found that increased asymmetry in the preoperative total CSA of deep neck paraspinal muscles at C3, C5, C6, and C7 significantly contributed to the risk of ASD development. Improvement of the paraspinal neck muscle condition and function preoperatively may reduce the incidence of ASD, but future studies are needed in this regard, given the limited evidence.

The current study findings have clinical implementations, and future research should focus on the impact of addressing the identified modifiable risk factors for ASD development. These risk factors may alter the distribution of stress in the cervical spine, thus predisposing the vertebral levels above and below the fused segment to quicker deterioration.^7,37 Yet, it remains unclear whether ASD is the result of raised mechanical stress on adjacent levels, a natural continuing process of degeneration, or a combination of the two factors.²⁶

This study has some limitations. First, all the included studies were retrospective in nature. Second, only three out of thirteen studies had “not serious” methodological bias, providing limited evidence for the identified risk factors. Third, preoperative diagnosis, number of operated levels, and the definition of ASD were inconsistent among the included studies. Fourth, single included studies reported significant radiographic risk factors for ASD development, but we could not perform a meta-analysis due to insufficient data.

Conclusion

This study found that decreased postoperative cervical lordosis, greater change in preoperative to postoperative cervical sagittal alignment, and developmental cervical canal stenosis are associated with an increased risk of developing ASD following ACDF.

Footnotes

Acknowledgments

This study was organized by AO Spine through the AO Spine Knowledge Forum Degenerative, a focused group of international spine degenerative experts. AO Spine is a clinical division of the AO Foundation, which is an independent medically-guided not-for-profit organization.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Disclosure

JCW - Royalties – Biomet, Seaspine, Synthes, Novapproach; Investments/Options – Bone Biologics, Pearldiver, Electrocore, Surgitech; Consulting: Bioretec, Angitia, Epidutech, Depuy; Board of Directors - AO Foundation, National Spine Health Foundation; Editorial Boards - Global Spine Journal Editor-in-Chief; Trips/Travel: AO Spine, NASS (non-financial, travel reimbursement for meetings); Fellowship Funding (paid to institution): AO Foundation; HJM – Royalties - Fehling Instruments GmbH; Consulting - Stayble Therapeutics, Mundipharma (both Via Regenerate Life Sciences GmbH); Stocks - Spinplant GmbH)STY – Grants: AO Spine, Empiric Spine; Royalties - Meditech Spine; Boards – AO Spine, ISSLS, Stocks – MedysseyPH – Royalties: Medtronic, Nuvasive, Zimmer Biomet; Board - NASS: ZB – Grants/ Research support: AO Spine (Paid directly to institution/employer); Medical Metrics (Paid directly to institution/employer); Nexus Spine (past, paid directly to institution/employer), MiMedx (past, paid directly to institution/employer), SBIR NIH (past, Paid directly to institution/employer); Medical Metrics (past, paid directly to institution/employer); Next Science (past, Paid directly to institution/employer); Consultancy: Next Science (paid directly to institution/employer); Scientific Advisory Board: Medtronic, Medical Metrics, DePuy Synthes; Trips/Travel: AO Spine, NASS (non-financial, travel reimbursement for meetings); Board of Directors: LSRS (Nonfinancial, Co-chair Program Committee); Committees: AO Spine Knowledge Forum Degenerative (Steering Committee Member); North American Spine Society: Research Project Management Committee (Vice chair), Section on Biologics & Basic Research (Co-chair), The Spine Journal Peer Reviewers (Committee member). Patents (issued): Biomarkers for painful intervertebral discs and methods of use thereof.

ORCID iDs

Mohamed Kamal Mesregah

Hans-Joerg Meisel

Patrick Hsieh

S. Tim Yoon

Zorica Buser

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