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The Correlation Between Postoperative Cervical Sagittal Alignment and Spine Sagittal Alignment in Adolescent Idiopathic Scoliosis: A Meta-Analysis
Journal Pre-proof The correlation between postoperative cervical sagittal alignment and spine sagittal alignment in adolescent idiopathic scoliosis: a meta-analysis Yonggang Fan, M.Med, Jie Wang, M.Med, Mandi Cai, M.Med, Xudong Wang, M.Med, Lei Xia, M.D PII:
S1878-8750(19)32682-8
DOI:
https://doi.org/10.1016/j.wneu.2019.10.064
Reference:
WNEU 13535
To appear in:
World Neurosurgery
Received Date: 7 September 2019 Revised Date:
9 October 2019
Accepted Date: 10 October 2019
Please cite this article as: Fan Y, Wang J, Cai M, Wang X, Xia L, The correlation between postoperative cervical sagittal alignment and spine sagittal alignment in adolescent idiopathic scoliosis: a metaanalysis, World Neurosurgery (2019), doi: https://doi.org/10.1016/j.wneu.2019.10.064. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Elsevier Inc. All rights reserved.
Title Page Title: The correlation between postoperative cervical sagittal alignment and spine sagittal alignment in adolescent idiopathic scoliosis: a meta-analysis Author names and affiliations: Yonggang Fan, M.Med, Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P. R. China. E-mail: [email protected] Jie Wang, M.Med, Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P. R. China. E-mail: [email protected] Yonggang Fan and Jie Wang contributed equally to this work. Mandi Cai, M.Med, Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P. R. China. E-mail: [email protected] Xudong Wang, M.Med, Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P. R. China. E-mail: [email protected]
Corresponding author: Lei Xia, M.D, Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P. R. China. E-mail: [email protected] Highest academic degrees for all authors: Yonggang Fan, M.Med; Jie Wang, M.Med; Lei Xia, M.D
Departmental and institutional affiliations for all authors: Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P. R. China Running title: The correlation between cervical and spine in adolescent idiopathic scoliosis: a meta-analysis Key words: Adolescent idiopathic scoliosis, Cervical alignment,Thoracic kyphosis, meta-analysis Abbreviations list: cervical lordosis, CL; adolescent idiopathic scoliosis, AIS; confidence intervals, Cis; thoracic kyphosis, TK; lumbar lordosis, LL; pelvic incidence, PI; pelvic tilt, PT; sacral slope,SS; Newcastle-Ottawa Scale (NOS)
Title: The correlation between postoperative cervical sagittal alignment and spine sagittal alignment in adolescent idiopathic scoliosis: a meta-analysis
Abstract Purpose To perform a meta-analysis exploring the correlation between the cervical lordosis (CL) and sagittal spine alignment in adolescent idiopathic scoliosis（AIS） patients after surgery for determining a surgical strategy. Methods We searched three electronic databases for studies discussing the correlation between CL and spine sagittal alignment in AIS patients. Studies published from the inception of the database to June 2019 were retrieved without any language restrictions. Summary correlation coefficient (r) values were extracted from each study, and 95% confidence intervals (CIs) were calculated. In addition, we conducted subgroup analyses in different curve type subgroups with at least two studies. Results Ten relevant studies involving 539 patients were evaluated in this meta-analysis. The Pearson correlation (r) for CL and the T1 slope was -0.69; (95% CI = -0.79 to -0.54). The fixed effects summary correlation between CL and thoracic kyphosis (TK) in patients was moderate (r =-0.40; 95% CI = -0.48 to -0.31). In addition, the fixed effects summary correlations between CL and lumbar lordosis (LL) (r = 0.19; 95% CI = 0.07 to 0.30), pelvic incidence (PI) (r =-0.08; 95% CI = -0.20 to 0.04), pelvic tilt (PT) (r =-0.06; 95% CI = -0.18 to 0.06), and sacral slope (SS) (r =-0.06; 95% CI = -0.18 to 0.06) in patients were weak. Conclusions There is a strong negative correlation between CL and the T1 slope in AIS patients. Given the lack of robust clinical evidence, these findings warrant verification by large prospective registries and randomized trials with long follow-up
periods. Key words: adolescent idiopathic scoliosis, cervical alignment, thoracic kyphosis, meta-analysis
TEXT Introduction Adolescent idiopathic scoliosis (AIS) is the most common type of spinal deformity that usually appears in the coronal and sagittal planes1. Approximately 2∼3% of adolescents meet the diagnostic criteria (Cobb angle >10° in the coronal plane) 2. To prevent curve progression and achieve a balanced spine, surgery continues to be the mainstay of treatment for AIS. For individuals with adolescent idiopathic scoliosis (AIS), surgery is generally recommended when the primary curve has a Cobb angle larger than 45°2, 3. Patients are treated by posterior or anterior instrumentation and fusion with all pedicle screw constructs, and a rod rotation maneuver is used for scoliosis correction in patients. Osteotomy procedures are performed to correct deformities in some patients with rigid scoliosis. Postoperative flattening or kyphosis of the cervical or thoracic spine in AIS patients has been reported4, 5. Changes in the sagittal imaging parameters of the cervical spine in patients with AIS after deformity correction have a significant impact on HRQOL6. Kyphotic malalignment of the cervical spine has been associated with axial neck pain and degenerative changes in cervical discs and facet joints7-9. Therefore, the restoration of the normal lordosis curvature in the cervical spine or the prevention of postoperative cervical kyphosis should be the basic objectives of AIS surgical correction. Understanding the correlation between postoperative cervical sagittal alignment and spine sagittal alignment is significant for determining a surgical strategy. The surgical strategy for patients with AIS is different according to the location of the major curve. Therefore, for patients with different curves, the extent of the surgery is different. The upper instrumented vertebra of patients with lumbar AIS is lower than that of patients with thoracic AIS, and thus, they have more unfused
vertebrae, potentially allowing more cranial compensatory capabilities. However, the relationship between cervical alignment and sagittal spine parameters in patients with AIS and different curve types remains controversial. To date, no systematic reviews or meta-analyses have been conducted to investigate this association. In this meta-analysis, our goal was to determine and evaluate the relationship between CL and spinal dysplasia parameters in AIS patients, especially the relationship between CL and TK and the T1 slope in individuals with different curve types. Methods Literature search strategy Two independent observers searched published studies in PubMed, EMBASE and the Cochrane Library databases. The retrieval time was from the inception of the database to June 2019, and there were no language restrictions. To achieve maximum sensitivity in the search strategy, the databases were searched using the following keywords and MeSH terms: “AIS OR adolescent idiopathic scoliosis,” AND “cervical OR sagittal alignment.” We also searched Google Scholar, and the literature we retrieved was assessed. Study selection The following inclusion criteria were used: (a) investigated the relationship between the CL and parameters of spinal dysplasia; (b) included patients with adolescent idiopathic scoliosis; (c) used one or more of following sagittal parameters: thoracic kyphosis (TK), T1 slope, lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS) or pelvic tilt (PT); and (d) provided correlation coefficients or odds ratios (ORs) as effect measures. Data extraction These data were extracted from the included studies by two reviewers independently,
and disagreements were resolved by consensus or, if necessary, by a third reviewer. Standardized tables were used to record the first author's name, duration of the study, country of study, sample size of each group, type of research, and curve type. The correlation coefficients at the final follow-up for the relationships between the thoracic kyphosis, T1 slope, lumbar lordosis, pelvic incidence, sacral slope, pelvic tilt, and cervical lordosis parameters were used as the primary outcomes. The outcome data were presented as Pearson or Spearman correlation coefficients or ORs. Quality assessment The quality of the included studies was assessed independently by two observers using the Newcastle-Ottawa Scale (NOS). The highest quality evaluation score was 9 stars. Studies with scores of 0 to 3, 4 to 6 and 7 or more were classified as having poor quality, medium quality, and high quality, respectively10. Data analysis Heterogeneity was evaluated using the χ2 test and I2 statistics. If the results of studies according to the internal analysis showed no statistical heterogeneity (p˃0.1, I2≤50%), a fixed effects model was performed; conversely, if there was statistical heterogeneity (p≤0.1, I2˃50%), a subgroup analysis was carried out according to the curve type to determine the source of clinical heterogeneity. A random effects model was performed if the source of statistical heterogeneity could not be determined. The results are presented as correlation coefficients with the corresponding 95% confidence intervals (CIs). The meta-regression models of the Pearson coefficients assessed each of the associations between TK, the T1 slope, LL, SS, PI, PT, and CL. In addition to the meta-regression, we conducted subgroup analyses in different curve type subgroups that had at least two studies. Fisher’s r-to-z transformation of the Pearson coefficients was conducted to obtain
variance-stabilized correlation coefficients. The transformed Pearson coefficients were used in a meta-regression and subgroup analysis. Pooled correlation coefficients were transformed back to the raw scale for presentation. A meta-analysis of the Spearman coefficients was not possible because their sampling variances could not be deduced from the data provided in studies11. The software STATA version 15 (Stata Corporation, College Station, TX, USA) was used for all data analyses. Results Search results The literature searched from PubMed, EMBASE, and the Cochrane library identified 1882 articles. The literature search procedure is shown in Figure 1. A total of 534 references were excluded because of duplication. After the titles and abstracts were screened, 1282 studies were directly excluded. The remaining 56 studies underwent a comprehensive full-text analysis. Finally, 10 comparative studies were included in the meta-analysis. Study characteristics The eligible studies included 10 cohort studies published in 2014–2018. Table 1 shows the overall study and patient characteristics. The ten studies included n = 539 patients in total and had sample sizes ranging from 29 to 89. The quality assessment was moderate in the 10 studies, according to the Newcastle–Ottawa scale (NOS). Of the studies, three scored 7 points, three scored 8 points, and four scored 9 points (Table 2). A score ≥ 7 indicated a good quality study; thus, the studies were of a relatively high quality. Clinical efficacy Correlation Between Cervical Sagittal Parameters In all studies, nine studies reported that the measure of CL was associated with TK
(Figure 2). Seven studies described correlations between CL and LL, SS, and the T1 slope (Figure 3). Six studies reported the relationships between CL and PI, PT. In all patients, the random effects summary correlation coefficient between CL and the T1 slope was strong (Pearson coefficient [r] = -0.69; 95% CI = -0.79 to-0.54). The fixed effects summary correlation between CL and TK in patients was moderate (r =-0.40; 95% CI = -0.48 to -0.31). In addition, the fixed effects summary correlations between CL and LL (r = 0.19; 95% CI = 0.07 to 0.30), PI (r =-0.08; 95% CI = -0.20 to 0.04), PT (r =-0.06; 95% CI = -0.18 to 0.06), and SS (r =-0.06; 95% CI = -0.18 to 0.06) in patients were weak. Curve type Using meta-regression and subgroup analysis, we assessed the potential impact of different curve patterns on the association between CL and TK and the T1 slope in AIS patients. There were no significant differences between T-AIS and L-AIS patients. Figure 1 and Figure 2 show the pooled r values for the different subgroup analyses. Discussion To the best of our knowledge, this is the first meta-analysis that explored the correlation between CL and sagittal spine parameters. In our systematic review and meta-analysis, CL was strongly associated with the T1 slope and moderately associated with TK in all populations observed. In AIS patients, the subgroup analyses showed that CL and the T1 slope and TK are equivalently correlated in T-AIS and L-AIS patients. The sagittal changes in the cervical spine after scoliosis correction and the relationship between the cervical sagittal alignment and the spinal parameters are well recognized. Legarreta et al.4 found that the C2-C7 Cobb angle changed significantly
after surgery; it ranged from being lordotic preoperatively (0.7°) to being kyphotic (5.6°) at the 2-year follow-up in Lenke 1 AIS patients. Hwang et al.12 reported that the occurrence of cervical kyphosis in Lenke 1 and 2 AIS patients increased from 27.3% preoperatively to 63.6% postoperatively. Therefore, a loss of the sagittal curvature in the cervical spine in patients with AIS may be related to scoliosis correction surgery. Some studies suggested that AIS patients often suffer from a loss of thoracic kyphosis after deformity correction6, 13-18. Postoperative thoracic kyphosis may lead to poor sagittal alignment of the cervical spine6, 13-18. In the correlation analysis in our study, the correlation between the spinal parameters, except for TK and the T1 slope, and CL was strong, but the relationship between other spinal parameters and CL was weak. Surgery significantly changed the sagittal alignment of the thoracic vertebrae (including TK and the T1 slope) and further induced CL changes. Thus, the change in CL is a kind of compensatory response that occurs after operation. The overall goal of a meta-analysis is to aggregate the results of previous studies to arrive at a summary conclusion about a body of research. It is most useful for summarizing prior research when the sample sizes of the individual studies in a specific area of research are insufficient to yield a valid outcome. Few studies have discussed the factors affecting CL in patients with different types of scoliosis. From the available data, this meta-analysis showed that there was no difference in the correlations between CL and TK, T1slope. In our study, we found that TK and the T1 slope were the factors that affected the development of cervical kyphosis after operation, where a larger TK and T1 slope corresponded to a smaller cervical kyphosis after surgery. Therefore, the changes in TK and the T1 slope should be taken into account in the preoperative evaluation of patients and the formulation of surgical strategies. Only in this way can the risk for
cervical kyphosis be minimized. There are some limitations to our meta-analysis. First, the number of patients in several of the included studies was relatively small, and the number of patients included for each curve type was relatively small, which may reduce the strength of the conclusions in this paper. Second, our meta-analysis was based only on published studies, which tend to only report positive or significant results; studies with insignificant or negative results are often rejected or are not submitted. This issue may have led to publication bias and an overestimation of the results. Finally, the level and type of surgical approach adopted by different surgeons may cause clinical heterogeneity in various treatment centers. CONCLUSIONS In summary, despite the limitations of our meta-analysis, all currently available evidence supports a strong negative correlation between cervical kyphosis and TK and the T1 slope. The correlation was similar for individuals with different curve types. Given the lack of robust clinical evidence, these findings warrant verification by large prospective registries and randomized trials with long follow-up periods.
Funding sources: The authors declare that they did not receive funding.
Conflicts of interest: None of the authors have potential conflicts of interest.
Figure Legends： Figure 1 Flow diagram of the study selection process
Figure 2 Pooled Pearson correlation coefficients from studies linking CL and TK in individuals with different curve types. Error bars indicate the 95% CIs. Figure 3 Pooled Pearson correlation coefficients from studies linking CL and the T1 slope in individuals with different curve types. Error bars indicate the 95% CIs.
References: 1. Stokes IA, Bigalow LC, Moreland MS. Three-dimensional spinal curvature in idiopathic scoliosis. Journal of orthopaedic research : official publication of the Orthopaedic Research Society. 1987;5(1): 102-113. https://doi.org/10.1002/jor.1100050113. 2. Weinstein SL, Dolan LA, Cheng JC, Danielsson A, Morcuende JA. Adolescent idiopathic scoliosis. Lancet. 2008;371(9623): 1527-1537. https://doi.org/10.1016/s0140-6736(08)60658-3. 3. Cheng JC, Castelein RM, Chu WC, et al. Adolescent idiopathic scoliosis. Nature Reviews Disease Primers. 2015;1(1): 15030. https://doi.org/10.1038/nrdp.2015.30. 4. Legarreta CA, Barrios C, Rositto GE, et al. Cervical and thoracic sagittal misalignment after surgery for adolescent idiopathic scoliosis: a comparative study of all pedicle screws versus hybrid instrumentation. Spine. 2014;39(16): 1330-1337. https://doi.org/10.1097/brs.0000000000000403. 5. Charles YP, Sfeir G, Matter-Parrat V, Sauleau EA, Steib JP. Cervical sagittal alignment in idiopathic scoliosis treated by posterior instrumentation and in situ bending. Spine. 2015;40(7): E419-427. https://doi.org/10.1097/brs.0000000000000767. 6. Youn MS, Shin JK, Goh TS, Kang SS, Jeon WK, Lee JS. Relationship between cervical sagittal alignment and health-related quality of life in adolescent idiopathic scoliosis. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. 2016;25(10): 3114-3119. https://doi.org/10.1007/s00586-016-4488-2. 7. Miyazaki M, Hymanson HJ, Morishita Y, et al. Kinematic Analysis of the Relationship Between Sagittal Alignment and Disc Degeneration in the Cervical Spine. 2008;33(23): E870-E876. https://doi.org/10.1097/BRS.0b013e3181839733. 8. Katsuura A, Hukuda S, Saruhashi Y, Mori KJESJ. Kyphotic malalignment after anterior cervical fusion is one of the factors promoting the degenerative process in adjacent intervertebral levels. 2001;10(4): 320-324. https://doi.org/10.1007/s005860000243. 9. Cochran T, Irstam L, Nachemson A. Long-term anatomic and functional changes in patients with adolescent idiopathic scoliosis treated by Harrington rod fusion. Spine. 1983;8(6): 576-584. https://doi.org/10.1097/00007632-198309000-00003. 10. Ma Z, Guo F, Qi J, Xiang W, Zhang J. Meta-analysis shows that obesity may be a significant risk factor for prosthetic joint infections. International orthopaedics. 2016;40(4): 659-667. https://doi.org/10.1007/s00264-015-2914-4. 11. Choi J, Joseph L, Pilote L. Obesity and C-reactive protein in various populations: a systematic review and meta-analysis. Obesity reviews : an official journal of the International Association for the Study of Obesity. 2013;14(3): 232-244. https://doi.org/10.1111/obr.12003. 12. Hwang SW, Samdani AF, Tantorski M, et al. Cervical sagittal plane decompensation after surgery for adolescent idiopathic scoliosis: an effect imparted by postoperative thoracic hypokyphosis. Journal of neurosurgery Spine. 2011;15(5): 491-496. https://doi.org/10.3171/2011.6.Spine1012. 13. Yan P, Zhang Y, Liu S, et al. Sagittal Profile Response of Cervical Spine After Posterior Correction in Thoracic and Lumbar Adolescent Idiopathic Scoliosis: Correlation with Thoracic Kyphosis? World neurosurgery. 2018;120: e333-e341. https://doi.org/10.1016/j.wneu.2018.08.071. 14. Luo SG, Zhong ZM, Zhu SY, Chen JT. The change of cervical sagittal alignment after surgery for adolescent idiopathic scoliosis. Clinical neurology and neurosurgery. 2018;171: 21-25. https://doi.org/10.1016/j.clineuro.2018.04.019. 15. Zhu C, Yang X, Zhou B, et al. Cervical kyphosis in patients with Lenke type 1 adolescent idiopathic scoliosis: the prediction of thoracic inlet angle. BMC musculoskeletal disorders. 2017;18(1): 220. https://doi.org/10.1186/s12891-017-1590-5. 16. Zhang Z, Liu Z, Zhu Z, Qiu Y. Predictors of ultimate postoperative cervical sagittal alignment in main thoracic adolescent idiopathic scoliosis: A long-term follow-up study. Medicine. 2017;96(49): e8799. https://doi.org/10.1097/md.0000000000008799.
17. Hiyama A, Sakai D, Watanabe M, Katoh H, Sato M, Mochida J. Sagittal alignment of the cervical spine in adolescent idiopathic scoliosis: a comparative study of 42 adolescents with idiopathic scoliosis and 24 normal adolescents. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. 2016;25(10): 3226-3233. https://doi.org/10.1007/s00586-016-4701-3. 18. Yagi M, Iizuka S, Hasegawa A, et al. Sagittal Cervical Alignment in Adolescent Idiopathic Scoliosis. Spine Deform. 2014;2(2): 122-130. https://doi.org/10.1016/j.jspd.2013.11.002. 19. Pesenti S, Blondel B, Peltier E, Choufani E, Bollini G, Jouve JL. Interest of T1 parameters for sagittal alignment evaluation of adolescent idiopathic scoliosis patients. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. 2016;25(2): 424-429. https://doi.org/10.1007/s00586-015-4244-z. 20. Zhao J, Chen Z, Yang M, Li G, Zhao Y, Li M. Does spinal fusion to T2, T3, or T4 affects sagittal alignment of the cervical spine in Lenke 1 AIS patients: A retrospective study. Medicine. 2018;97(5): e9764. https://doi.org/10.1097/md.0000000000009764. 21. Wang F, Zhou XY, Xu XM, et al. Cervical Sagittal Alignment Limited Adjustment After Selective Posterior Thoracolumbar/Lumbar Curve Correction in Patients With Lenke Type 5C Adolescent Idiopathic Scoliosis. Spine. 2017;42(9): E539-e546. https://doi.org/10.1097/brs.0000000000001906.
Table I. The baseline characteristics of the two groups First Year Country Design N Curve type author Yagi18 2014 Japan Retrospective 89 T-AIS +L-AIS Zhang16 2017 China Retrospective 44 T-AIS 19 Pesenti 2016 France Retrospective 29 T-AIS Zhao20 2018 China Retrospective 64 T-AIS 13 Yan 2018 China Retrospective 82 T-AIS+L-AIS Youn6 2016 Korea Retrospective 67 T-AIS Wang21 2017 China Retrospective 67 L-AIS 15 Zhu 2017 China Retrospective 50 T-AIS Luo14 2018 China Retrospective 46 T-AIS+L-AIS 17 Hiyama 2016 Japan Retrospective 38 T-AIS T-AIS, thoracic-curve adolescent idiopathic scoliosis; L-AIS, lumbar-curve adolescent idiopathic scoliosis; N, number of patients
Table . Methodological quality of the studies included in the meta-analysis. Author Year Level of Selectio Compara- Outcome Quality evidence n bility s judgment 18 Yagi et al. 2014 4 1 2 7 Zhang et al.16
2017
4
1
3
8
Pesenti et al.19 Zhao et al.20
2016
4
2
2
8
2018
4
2
2
8
Yan et al.13
2018
4
2
3
9
Youn et al.6
2016
4
2
3
9
Wang et al.21
2017
4
2
3
9
Zhu et al.15
2017
4
2
3
9
Luo et al.14
2018
4
1
2
7
2016 Hiyama et 4 1 2 7 17 al. Selection: (1) representativeness of the exposed cohort, (2) selection of the nonexposed cohort, (3) ascertainment of exposure and (4) demonstration that the outcome of interest was not present at the start of study Comparability: comparability of the cohorts based on the design or analysis Outcome: (1) assessment outcome, (2) follow-up sufficiently long for outcomes to occur, (3) adequate follow-up periods for the cohorts (≥ 1 year) NOS scores ≥ 7 indicate a high-quality study
S1878-8750(19)32682-8
DOI:
https://doi.org/10.1016/j.wneu.2019.10.064
Reference:
WNEU 13535
To appear in:
World Neurosurgery
Received Date: 7 September 2019 Revised Date:
9 October 2019
Accepted Date: 10 October 2019
Please cite this article as: Fan Y, Wang J, Cai M, Wang X, Xia L, The correlation between postoperative cervical sagittal alignment and spine sagittal alignment in adolescent idiopathic scoliosis: a metaanalysis, World Neurosurgery (2019), doi: https://doi.org/10.1016/j.wneu.2019.10.064. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Elsevier Inc. All rights reserved.
Title Page Title: The correlation between postoperative cervical sagittal alignment and spine sagittal alignment in adolescent idiopathic scoliosis: a meta-analysis Author names and affiliations: Yonggang Fan, M.Med, Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P. R. China. E-mail: [email protected] Jie Wang, M.Med, Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P. R. China. E-mail: [email protected] Yonggang Fan and Jie Wang contributed equally to this work. Mandi Cai, M.Med, Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P. R. China. E-mail: [email protected] Xudong Wang, M.Med, Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P. R. China. E-mail: [email protected]
Corresponding author: Lei Xia, M.D, Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P. R. China. E-mail: [email protected] Highest academic degrees for all authors: Yonggang Fan, M.Med; Jie Wang, M.Med; Lei Xia, M.D
Departmental and institutional affiliations for all authors: Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P. R. China Running title: The correlation between cervical and spine in adolescent idiopathic scoliosis: a meta-analysis Key words: Adolescent idiopathic scoliosis, Cervical alignment,Thoracic kyphosis, meta-analysis Abbreviations list: cervical lordosis, CL; adolescent idiopathic scoliosis, AIS; confidence intervals, Cis; thoracic kyphosis, TK; lumbar lordosis, LL; pelvic incidence, PI; pelvic tilt, PT; sacral slope,SS; Newcastle-Ottawa Scale (NOS)
Title: The correlation between postoperative cervical sagittal alignment and spine sagittal alignment in adolescent idiopathic scoliosis: a meta-analysis
Abstract Purpose To perform a meta-analysis exploring the correlation between the cervical lordosis (CL) and sagittal spine alignment in adolescent idiopathic scoliosis（AIS） patients after surgery for determining a surgical strategy. Methods We searched three electronic databases for studies discussing the correlation between CL and spine sagittal alignment in AIS patients. Studies published from the inception of the database to June 2019 were retrieved without any language restrictions. Summary correlation coefficient (r) values were extracted from each study, and 95% confidence intervals (CIs) were calculated. In addition, we conducted subgroup analyses in different curve type subgroups with at least two studies. Results Ten relevant studies involving 539 patients were evaluated in this meta-analysis. The Pearson correlation (r) for CL and the T1 slope was -0.69; (95% CI = -0.79 to -0.54). The fixed effects summary correlation between CL and thoracic kyphosis (TK) in patients was moderate (r =-0.40; 95% CI = -0.48 to -0.31). In addition, the fixed effects summary correlations between CL and lumbar lordosis (LL) (r = 0.19; 95% CI = 0.07 to 0.30), pelvic incidence (PI) (r =-0.08; 95% CI = -0.20 to 0.04), pelvic tilt (PT) (r =-0.06; 95% CI = -0.18 to 0.06), and sacral slope (SS) (r =-0.06; 95% CI = -0.18 to 0.06) in patients were weak. Conclusions There is a strong negative correlation between CL and the T1 slope in AIS patients. Given the lack of robust clinical evidence, these findings warrant verification by large prospective registries and randomized trials with long follow-up
periods. Key words: adolescent idiopathic scoliosis, cervical alignment, thoracic kyphosis, meta-analysis
TEXT Introduction Adolescent idiopathic scoliosis (AIS) is the most common type of spinal deformity that usually appears in the coronal and sagittal planes1. Approximately 2∼3% of adolescents meet the diagnostic criteria (Cobb angle >10° in the coronal plane) 2. To prevent curve progression and achieve a balanced spine, surgery continues to be the mainstay of treatment for AIS. For individuals with adolescent idiopathic scoliosis (AIS), surgery is generally recommended when the primary curve has a Cobb angle larger than 45°2, 3. Patients are treated by posterior or anterior instrumentation and fusion with all pedicle screw constructs, and a rod rotation maneuver is used for scoliosis correction in patients. Osteotomy procedures are performed to correct deformities in some patients with rigid scoliosis. Postoperative flattening or kyphosis of the cervical or thoracic spine in AIS patients has been reported4, 5. Changes in the sagittal imaging parameters of the cervical spine in patients with AIS after deformity correction have a significant impact on HRQOL6. Kyphotic malalignment of the cervical spine has been associated with axial neck pain and degenerative changes in cervical discs and facet joints7-9. Therefore, the restoration of the normal lordosis curvature in the cervical spine or the prevention of postoperative cervical kyphosis should be the basic objectives of AIS surgical correction. Understanding the correlation between postoperative cervical sagittal alignment and spine sagittal alignment is significant for determining a surgical strategy. The surgical strategy for patients with AIS is different according to the location of the major curve. Therefore, for patients with different curves, the extent of the surgery is different. The upper instrumented vertebra of patients with lumbar AIS is lower than that of patients with thoracic AIS, and thus, they have more unfused
vertebrae, potentially allowing more cranial compensatory capabilities. However, the relationship between cervical alignment and sagittal spine parameters in patients with AIS and different curve types remains controversial. To date, no systematic reviews or meta-analyses have been conducted to investigate this association. In this meta-analysis, our goal was to determine and evaluate the relationship between CL and spinal dysplasia parameters in AIS patients, especially the relationship between CL and TK and the T1 slope in individuals with different curve types. Methods Literature search strategy Two independent observers searched published studies in PubMed, EMBASE and the Cochrane Library databases. The retrieval time was from the inception of the database to June 2019, and there were no language restrictions. To achieve maximum sensitivity in the search strategy, the databases were searched using the following keywords and MeSH terms: “AIS OR adolescent idiopathic scoliosis,” AND “cervical OR sagittal alignment.” We also searched Google Scholar, and the literature we retrieved was assessed. Study selection The following inclusion criteria were used: (a) investigated the relationship between the CL and parameters of spinal dysplasia; (b) included patients with adolescent idiopathic scoliosis; (c) used one or more of following sagittal parameters: thoracic kyphosis (TK), T1 slope, lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS) or pelvic tilt (PT); and (d) provided correlation coefficients or odds ratios (ORs) as effect measures. Data extraction These data were extracted from the included studies by two reviewers independently,
and disagreements were resolved by consensus or, if necessary, by a third reviewer. Standardized tables were used to record the first author's name, duration of the study, country of study, sample size of each group, type of research, and curve type. The correlation coefficients at the final follow-up for the relationships between the thoracic kyphosis, T1 slope, lumbar lordosis, pelvic incidence, sacral slope, pelvic tilt, and cervical lordosis parameters were used as the primary outcomes. The outcome data were presented as Pearson or Spearman correlation coefficients or ORs. Quality assessment The quality of the included studies was assessed independently by two observers using the Newcastle-Ottawa Scale (NOS). The highest quality evaluation score was 9 stars. Studies with scores of 0 to 3, 4 to 6 and 7 or more were classified as having poor quality, medium quality, and high quality, respectively10. Data analysis Heterogeneity was evaluated using the χ2 test and I2 statistics. If the results of studies according to the internal analysis showed no statistical heterogeneity (p˃0.1, I2≤50%), a fixed effects model was performed; conversely, if there was statistical heterogeneity (p≤0.1, I2˃50%), a subgroup analysis was carried out according to the curve type to determine the source of clinical heterogeneity. A random effects model was performed if the source of statistical heterogeneity could not be determined. The results are presented as correlation coefficients with the corresponding 95% confidence intervals (CIs). The meta-regression models of the Pearson coefficients assessed each of the associations between TK, the T1 slope, LL, SS, PI, PT, and CL. In addition to the meta-regression, we conducted subgroup analyses in different curve type subgroups that had at least two studies. Fisher’s r-to-z transformation of the Pearson coefficients was conducted to obtain
variance-stabilized correlation coefficients. The transformed Pearson coefficients were used in a meta-regression and subgroup analysis. Pooled correlation coefficients were transformed back to the raw scale for presentation. A meta-analysis of the Spearman coefficients was not possible because their sampling variances could not be deduced from the data provided in studies11. The software STATA version 15 (Stata Corporation, College Station, TX, USA) was used for all data analyses. Results Search results The literature searched from PubMed, EMBASE, and the Cochrane library identified 1882 articles. The literature search procedure is shown in Figure 1. A total of 534 references were excluded because of duplication. After the titles and abstracts were screened, 1282 studies were directly excluded. The remaining 56 studies underwent a comprehensive full-text analysis. Finally, 10 comparative studies were included in the meta-analysis. Study characteristics The eligible studies included 10 cohort studies published in 2014–2018. Table 1 shows the overall study and patient characteristics. The ten studies included n = 539 patients in total and had sample sizes ranging from 29 to 89. The quality assessment was moderate in the 10 studies, according to the Newcastle–Ottawa scale (NOS). Of the studies, three scored 7 points, three scored 8 points, and four scored 9 points (Table 2). A score ≥ 7 indicated a good quality study; thus, the studies were of a relatively high quality. Clinical efficacy Correlation Between Cervical Sagittal Parameters In all studies, nine studies reported that the measure of CL was associated with TK
(Figure 2). Seven studies described correlations between CL and LL, SS, and the T1 slope (Figure 3). Six studies reported the relationships between CL and PI, PT. In all patients, the random effects summary correlation coefficient between CL and the T1 slope was strong (Pearson coefficient [r] = -0.69; 95% CI = -0.79 to-0.54). The fixed effects summary correlation between CL and TK in patients was moderate (r =-0.40; 95% CI = -0.48 to -0.31). In addition, the fixed effects summary correlations between CL and LL (r = 0.19; 95% CI = 0.07 to 0.30), PI (r =-0.08; 95% CI = -0.20 to 0.04), PT (r =-0.06; 95% CI = -0.18 to 0.06), and SS (r =-0.06; 95% CI = -0.18 to 0.06) in patients were weak. Curve type Using meta-regression and subgroup analysis, we assessed the potential impact of different curve patterns on the association between CL and TK and the T1 slope in AIS patients. There were no significant differences between T-AIS and L-AIS patients. Figure 1 and Figure 2 show the pooled r values for the different subgroup analyses. Discussion To the best of our knowledge, this is the first meta-analysis that explored the correlation between CL and sagittal spine parameters. In our systematic review and meta-analysis, CL was strongly associated with the T1 slope and moderately associated with TK in all populations observed. In AIS patients, the subgroup analyses showed that CL and the T1 slope and TK are equivalently correlated in T-AIS and L-AIS patients. The sagittal changes in the cervical spine after scoliosis correction and the relationship between the cervical sagittal alignment and the spinal parameters are well recognized. Legarreta et al.4 found that the C2-C7 Cobb angle changed significantly
after surgery; it ranged from being lordotic preoperatively (0.7°) to being kyphotic (5.6°) at the 2-year follow-up in Lenke 1 AIS patients. Hwang et al.12 reported that the occurrence of cervical kyphosis in Lenke 1 and 2 AIS patients increased from 27.3% preoperatively to 63.6% postoperatively. Therefore, a loss of the sagittal curvature in the cervical spine in patients with AIS may be related to scoliosis correction surgery. Some studies suggested that AIS patients often suffer from a loss of thoracic kyphosis after deformity correction6, 13-18. Postoperative thoracic kyphosis may lead to poor sagittal alignment of the cervical spine6, 13-18. In the correlation analysis in our study, the correlation between the spinal parameters, except for TK and the T1 slope, and CL was strong, but the relationship between other spinal parameters and CL was weak. Surgery significantly changed the sagittal alignment of the thoracic vertebrae (including TK and the T1 slope) and further induced CL changes. Thus, the change in CL is a kind of compensatory response that occurs after operation. The overall goal of a meta-analysis is to aggregate the results of previous studies to arrive at a summary conclusion about a body of research. It is most useful for summarizing prior research when the sample sizes of the individual studies in a specific area of research are insufficient to yield a valid outcome. Few studies have discussed the factors affecting CL in patients with different types of scoliosis. From the available data, this meta-analysis showed that there was no difference in the correlations between CL and TK, T1slope. In our study, we found that TK and the T1 slope were the factors that affected the development of cervical kyphosis after operation, where a larger TK and T1 slope corresponded to a smaller cervical kyphosis after surgery. Therefore, the changes in TK and the T1 slope should be taken into account in the preoperative evaluation of patients and the formulation of surgical strategies. Only in this way can the risk for
cervical kyphosis be minimized. There are some limitations to our meta-analysis. First, the number of patients in several of the included studies was relatively small, and the number of patients included for each curve type was relatively small, which may reduce the strength of the conclusions in this paper. Second, our meta-analysis was based only on published studies, which tend to only report positive or significant results; studies with insignificant or negative results are often rejected or are not submitted. This issue may have led to publication bias and an overestimation of the results. Finally, the level and type of surgical approach adopted by different surgeons may cause clinical heterogeneity in various treatment centers. CONCLUSIONS In summary, despite the limitations of our meta-analysis, all currently available evidence supports a strong negative correlation between cervical kyphosis and TK and the T1 slope. The correlation was similar for individuals with different curve types. Given the lack of robust clinical evidence, these findings warrant verification by large prospective registries and randomized trials with long follow-up periods.
Funding sources: The authors declare that they did not receive funding.
Conflicts of interest: None of the authors have potential conflicts of interest.
Figure Legends： Figure 1 Flow diagram of the study selection process
Figure 2 Pooled Pearson correlation coefficients from studies linking CL and TK in individuals with different curve types. Error bars indicate the 95% CIs. Figure 3 Pooled Pearson correlation coefficients from studies linking CL and the T1 slope in individuals with different curve types. Error bars indicate the 95% CIs.
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Table I. The baseline characteristics of the two groups First Year Country Design N Curve type author Yagi18 2014 Japan Retrospective 89 T-AIS +L-AIS Zhang16 2017 China Retrospective 44 T-AIS 19 Pesenti 2016 France Retrospective 29 T-AIS Zhao20 2018 China Retrospective 64 T-AIS 13 Yan 2018 China Retrospective 82 T-AIS+L-AIS Youn6 2016 Korea Retrospective 67 T-AIS Wang21 2017 China Retrospective 67 L-AIS 15 Zhu 2017 China Retrospective 50 T-AIS Luo14 2018 China Retrospective 46 T-AIS+L-AIS 17 Hiyama 2016 Japan Retrospective 38 T-AIS T-AIS, thoracic-curve adolescent idiopathic scoliosis; L-AIS, lumbar-curve adolescent idiopathic scoliosis; N, number of patients
Table . Methodological quality of the studies included in the meta-analysis. Author Year Level of Selectio Compara- Outcome Quality evidence n bility s judgment 18 Yagi et al. 2014 4 1 2 7 Zhang et al.16
2017
4
1
3
8
Pesenti et al.19 Zhao et al.20
2016
4
2
2
8
2018
4
2
2
8
Yan et al.13
2018
4
2
3
9
Youn et al.6
2016
4
2
3
9
Wang et al.21
2017
4
2
3
9
Zhu et al.15
2017
4
2
3
9
Luo et al.14
2018
4
1
2
7
2016 Hiyama et 4 1 2 7 17 al. Selection: (1) representativeness of the exposed cohort, (2) selection of the nonexposed cohort, (3) ascertainment of exposure and (4) demonstration that the outcome of interest was not present at the start of study Comparability: comparability of the cohorts based on the design or analysis Outcome: (1) assessment outcome, (2) follow-up sufficiently long for outcomes to occur, (3) adequate follow-up periods for the cohorts (≥ 1 year) NOS scores ≥ 7 indicate a high-quality study