Postoperative residual neuropathic pain prevents return to work after cervical OPLL surgery: nationwide multicenter study

Abstract

Cervical ossification of the posterior longitudinal ligament of the spine (c-OPLL) is an intractable disease that impairs activities of daily living and quality of life. There are few reports on patients’ return to work (RTW) after surgery. The aim of this study was to investigate the RTW status and its associated factors after c-OPLL surgery through a nationwide multicenter questionnaire survey and to provide reference evidence for determining the future treatment of this disease. We were able to study 286 patients (205 males, 81 females) from 13 institutions. We analyzed RTW in 198 patients, excluding 88 patients who were unemployed before surgery. RTW was confirmed in 151 patients (124 males, 27 females), and RTW rate was 76.3%. Significant differences were observed between RTW + and—groups in age, body mass index, preoperative workload, and preoperative JOA score. Notably, this study was the first to demonstrate that postoperative residual neuropathic pain is a significant factor associated with RTW after c-OPLL surgery. The results of this study will provide useful information for determining future treatment plans for patients with an eye toward returning to work after surgery, and may also have an impact on surgical indications for this disease.

Introduction

Ossification of the posterior longitudinal ligament of the spine (OPLL), first described by Key in 1838¹, is characterized by the heterotopic bone formation in the posterior longitudinal ligament of the spine. Cervical OPLL (c-OPLL) can result in neurological compromises through compression of spinal cord and nerve roots^2,3. C-OPLL is an intractable disease that reduces activities of daily living (ADL) and quality of life (QOL) and results in economic losses.

Due to its high relevance for the individual and society, return to work (RTW) has become an important outcome measure in recent years⁴. There are various reports regarding RTW after surgery for lumbar degenerative disease⁵, but there are significantly fewer reports regarding those for cervical degenerative disease⁶. Although there is a significant increase in evidence supporting the effectiveness of surgery in c-OPLL^2,3, there are very few reports on postoperative QOL⁷, and even fewer on postoperative RTW. RTW following surgery not only has positive effects for the individual patient but also for society in general. A better understanding of the factors that determine which patients are more (or less) likely to return to work after surgery may improve physician–patient communication in clinical practice and allow surgeons to quantify expectations throughout treatment.

The purpose of this study was to investigate the RTW status and its associated factors after c-OPLL surgery through a nationwide multicenter study and to provide reference evidence for determining the future treatment of this disease.

Results

In the present study, 151 patients (124 males and 27 females) out of 198 patients (160 males, 38 females) who were employed preoperatively were able to return to work, for a RTW rate of 76.3%. Patient demographics for the RTW + /- groups are shown in Table 1. Significant differences were observed between the two groups in age, body mass index (BMI), preoperative workload, and preoperative Japanese Orthopaedic Association (JOA) score. The RTW + group was significantly younger, had a significantly lower BMI, had a significantly higher preoperative workload, and had a significantly better preoperative JOA score. There were no significant differences in history of diabetes, cerebrovascular disease, or spinal surgery at other sites. In the postoperative RTW + group, 81.5% of patients were employed full-time, compared with 78.7% in the postoperative RTW- group with no significant difference between the two groups (Table 2). The occupations before surgery were light sedentary labor for 92 patients, light standing labor for 57 patients, and heavy labor for 49 patients. There were no significant differences in the distribution of the occupation categories in RTW + /- group (Table 2). Kaplan–Meier curves showed cumulative RTW rates, with a median time to RTW of 120 ± 15.4 days (Fig. 1).

Table 1.

Demographics of the participants with and without return to work.

	RTW + (n = 151)	RTW—(n = 47)	p-value
Gender (Male) (%)	82.1	76.6	0.40
Age (years)	59.7 ± 10.6	66.0 ± 10.1	< 0.001
Body mass index (kg/m2)	27.0 ± 5.37	25.1 ± 3.16	0.004
Diabetes mellitus (%)	27.8	42.6	0.072
Cerebrovascular disease (%)	3.31	2.13	1.00
Spine surgery of other sites (%)	11.9	21.3	0.15
Preoperative workload (%)	76.1 ± 27.8	53.5 ± 40.3	0.001
Preoperative disease duration (Month)	24.9 ± 40.2	37.6 ± 63.2	0.20
Full-time worker (%)	81.5	78.7	0.13
Preoperative JOA score	11.4 ± 2.79	9.33 ± 2.91	< 0.001

RTW return to work, JOA Japanese Orthopaedic Association.

Table 2.

Proportion of the preoperative occupation categories in RTW + /- group.

	RTW + (n = 151)	RTW—(n = 47)	p-value
Full-time employment (%)	81.5	78.7	0.47
Occupation categories			0.096
Light sedentary labor	74	18
Light standing labor	41	16
Heavy labor	36	13

RTW return to work.

Fig. 1.

Kaplan–Meier curve for cumulative return to work rate after surgery for cervical ossification of the posterior longitudinal ligament.

Radiographical assessments revealed that alignment of cervical spine, K-line condition, spinal canal occupying ratio (COR), the presence of an intramedullary signal intensity change on T2-weighted magnetic resonance (MR) imaging, and type of OPLL were not significantly different between the two groups (Table 3). The RTW + group had significantly better scores in all postoperative Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) domains (Table 4).

Table 3.

Radiographical assessments in RTW + /- group.

	RTW + (n = 151)	RTW—(n = 47)	p-value
Cervical lordosis angle	7.32 ± 11.2	10.4 ± 12.2	0.11
Spinal canal occupying ratio (%)	42.6 ± 17.3	47.2 ± 16.9	0.11
K-line (-) (%)	30.5	40.4	0.31
T2 high (%)	72.2	85.1	0.19
OPLL type			0.61
Segmental (%)	49.0	40.4	–
Mixed (%)	40.4	51.1	–
Continuous (%)	9.3	8.5	–
Localized (%)	1.3	0.0	–

RTW return to work, OPLL ossification of the posterior longitudinal ligament, T2 high: intramedullary high intensity area on T2-weighted images. Cervical lordosis angle and spinal canal occupying ratio were represented by mean ± standard deviation.

Table 4.

Comparison of JOACMEQ in RTW + /- group.

	RTW + (n = 151)	RTW—(n = 47)	p-value
Cervical spine function	61.2 ± 31.5	50.1 ± 30.4	0.023
Upper extremity function	84.5 ± 17.0	69.9 ± 22.1	< 0.001
Lower extremity function	73.1 ± 26.7	46.3 ± 28.0	< 0.001
Bladder function	77.2 ± 20.9	65.2 ± 22.0	0.001
Quality of life	55.7 ± 19.9	42.9 ± 15. 2	< 0.001

JOACMEQ Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire, RTW return to work.

The surgical procedures performed were laminoplasty (LMP), posterior decompression and fusion (PDF), anterior decompression and fusion (ADF), and anterior–posterior combined surgery (AP combined). To clarify the impact of surgical procedures on patients’ RTW, we investigated the distribution of surgical procedures according to whether or not patients returned to work (Table 5). There was no significant difference in the distribution of surgical procedures between those who returned to work and those who did not.

Table 5.

Distribution of surgical procedures in RTW + /- groups.

Surgical procedures	RTW + (n = 151)	RTW—(n = 47)	p-value
LMP	82	21	0.40
PDF	33	16	–
ADF	31	9	–
AP combined	5	1	–

RTW return to work, LMP laminoplasty, PDF posterior decompression and fusion, ADF anterior decompression and fusion, AP combined anterior–posterior combined surgery.

To investigate the association between postoperative residual pain and RTW, this study used the pain items from the JOACMEQ and the painDETECT Questionnaire (PDQ). According to the visual analog scale (VAS) assessment of pain in JOACMEQ, VAS values were significantly higher in the RTW- group, except for chest tightness (Table 6). Evaluation by PDQ showed that postoperative residual neuropathic pain (NeP) was significantly higher in the RTW- group (Table 6).

Table 6.

Postoperative residual pain (VAS scores) and RTW.

	RTW + (n = 151)	RTW—(n = 47)	p-value
Pain or stiffness in neck or shoulders	3.29 ± 3.15	4.78 ± 2.94	0.005
Tightness in chest	1.89 ± 2.67	2.68 ± 3.34	0.15
Pain or numbness in arms or hands	3.74 ± 3.26	5.28 ± 3.01	0.004
Pain or numbness from chest to toe	3.07 ± 3.10	4.58 ± 3.15	0.016
NeP ( +) (%)	22.8	42.5	0.025

RTW return to work, NeP neuropathic pain.

To elucidate the associated factors for success in achieving postoperative RTW, we employed multivariate logistic analysis. Multivariate analysis revealed that age, preoperative workload, preoperative JOA score, and postoperative residual NeP were independent factors significantly associated with RTW after c-OPLL surgery (Table 7).

Table 7.

Multivariate analysis to determine factors associated with RTW after cervical OPLL surgery.

Candidate	OR (95%CI)	p-value
Age	0.94 (0.91–0.98)	0.004
Gender	0.54 (0.18–1.60)	0.26
BMI	1.04 (0.94–1.16)	0.44
Pre JOA score	1.25 (1.08–1.46)	0.004
Pre workload	1.01 (1.00–1.03)	0.045
NeP	0.28 (0.12–0.69	0.006

RTW return to work, OR odds ratio, CI confidence interval, BMI body mass index, Pre preoperative, JOA Japanese Orthopaedic Association, NeP neuropathic pain.

Discussion

This is the first nationwide multicenter study on RTW after surgery for c-OPLL. In addition, this study is the first to demonstrate the impact of postoperative residual pain including NeP on RTW after c-OPLL surgery.

There are various reports regarding RTW after surgery for lumbar degenerative disease⁵, but there are significantly fewer reports regarding those for cervical degenerative disease⁶. The RTW rate after surgery in patients with degenerative cervical disease has been reported to be approximately 60% to 80%, although this varies depending on the cohort and the time of evaluation^4,8–10.

There are even fewer reports on RTW after c-OPLL surgery. To the best of our knowledge, there is only one English literature on RTW after c-OPLL surgery¹¹. In 2003, Kamizono et al. reported on the postoperative RTW of patients who underwent surgical treatment for c-OPLL using exclusively open-door LMP¹¹. The study included postoperative patients from a single institution who were aged 70 years or younger at the time of surgery, excluding patients who had been involved in traffic- or work-related accidents. The authors reported that the RTW rate after surgery was 53%, with lower rates in those who performed heavy labor, worked at heights, or drove professionally. Occupation, pre- and postoperative severity of myelopathy were significantly correlated with RTW, and they suggested that these factors can serve as a reference when designing postoperative vocational rehabilitation programs.

On the other hand, the present study is a nationwide multicenter study, and there are no restrictions on age or surgical procedure as long as the patient was employed before surgery. The RTW rate in the present study was 76.3%, which is higher than that reported by Kamizono et al.; however, due to differences in the cohorts studied, definitions of RTW, and the eras studied, it is inherently difficult to directly compare RTW rates across studies. Furthermore, we believe that it is more important to understand the factors associated with RTW than to compare RTW rates themselves. Previous reports in cervical degenerative disease have shown that factors such as employment immediately before surgery, younger age, having a high level of education, full-time employment, low-intensity occupation, short duration of symptoms, and not receiving worker’s compensation are favorable for RTW after cervical spine surgery^4,12,13. In the present study, multivariate analysis revealed that age, preoperative workload, preoperative JOA score, and postoperative residual NeP were independent factors significantly associated with RTW after c-OPLL surgery. Previous reports on degenerative cervical myelopathy have shown the significant advantage of anterior cervical surgery for RTW¹², but this study did not find any significant differences between surgical procedures. One of the likely explanations for this result is that the participating centers were experts in treating c-OPLL, and appropriate surgical procedures may have been selected for each case. Another likely explanation is the evolution of surgical procedures. The most common surgical procedure for cervical OPLL is LMP^2,3. However, patients with thick ossification and/or kyphosis (i.e., K-line—patients) have poor neurological recovery after LMP^14,15. Even in such patients, ADF can ideally relieve spinal cord compression by directly removing the OPLL, resulting in good postoperative recovery¹⁶. However, ADF for c-OPLL tends to be less popular due to its technical complexity and the complicated perioperative management, such as complications specific to anterior surgery (e.g., swallowing disorders, respiratory disorders, etc.)^16,17. With the recent advances in spinal instrumentation surgery, PDF has become a possible alternative procedure for K-line—c-OPLL^14,18. Further investigation is needed to determine the impact of changes in surgical procedures for c-OPLL on postoperative RTW.

In recent years, research into pain in c-OPLL has attracted the attention of researchers in this field. Neck pain after c-OPLL surgery is well recognized as one of the unresolved postoperative complications. It has been reported that factors affecting neck pain after c-OPLL surgery are related to neurological recovery, which is associated with its reduction¹⁹, and posterior cervical surgery and the number of fusion levels, which is associated with its worsening²⁰. More recent studies have reported a high prevalence of residual NeP after c-OPLL surgery, with risk factors including older age, longer duration of disease, poor preoperative JOA score, and low cervical lordotic angle^21,22. These results suggest that improving residual neck pain and NeP after c-OPLL surgery is a very important issue. Indeed, it has been reported that poor pain control after elective spine surgery was an independent risk factor for poor surgical outcome²³. Over the past two decades, significant progress has been made in developing algorithms and tools for the diagnosis of NeP; however, NeP remains a significant problem without an effective solution for all patients²⁴. Establishing a treatment for NeP is a challenge that we must overcome in the near future.

Despite extensive clinical research into degenerative cervical myelopathy, consensus regarding the optimal timing of surgical intervention remains controversial^25,26. Guidelines for degenerative cervical myelopathy strongly recommend surgical treatment for patients with spinal cord compression with moderate to severe myelopathy²⁵. However, recommendations for surgical treatment for the patients with mildly symptomatic or asymptomatic spinal cord compression have not yet been established. Although there is less evidence about c-OPLL than about “general” cervical degenerative diseases, studies of its natural history have shown that it exhibits a progressive nature of ossifying lesions²⁷. Furthermore, it has been reported that compared with “general” degenerative cervical myelopathy, c-OPLL may be at higher risk of worsening myelopathy after minor trauma²⁸. Given this background, the surgical indications for c-OPLL may differ from those for “general” degenerative cervical myelopathy. In the current clinical practice guidelines on the management of ossification of the spinal ligament², consistent with recommendations for surgical treatment for patients with “general” cervical degenerative disease, surgery is recommended for patients with moderate and/or progressive myelopathy due to c-OPLL. On the other hand, prophylactic surgery in patients with asymptomatic or mildly symptomatic c-OPLL should be undertaken with caution, as there is no evidence to recommend such treatment². In addition, while the current clinical practice guidelines on the management of ossification of the spinal ligament mention conservative treatment for c-OPLL, they do not mention postoperative rehabilitation programs or RTW². Median RTW time in the present study was 120 ± 15.4 days. We believe this information is important for planning treatment for patients who aim to return to work after surgical treatment for C-OPLL, but further evidence is needed.

In the literature regarding RTW after “general” cervical degenerative myelopathy^12,26, and in our current study, age and preoperative neurological symptoms appear to be consistently the factors most influencing RTW after cervical spine surgery. Furthermore, the results of this study revealed that postoperative residual NeP after c-OPLL surgery is one of the independent factors that affects postoperative RTW. It has been reported that age and preoperative neurological symptoms have a significant impact on postoperative residual NeP^21,22. Taking all these results into account, if one of the goals after c-OPLL surgery is RTW, it may be advisable to consider surgical treatment at a younger age before neurological symptoms worsen. To prove this, a further study with a larger number of cases and consistent backgrounds is needed.

Otherwise, several limitations of this study must be noted. First, the number of cases is limited. However, this is the first nationwide multicenter study on RTW after surgery for c-OPLL. We believe that this study, which involves nationwide participation from facilities primarily involved in the treatment of this disease, ensures a relatively representative sample and reduces bias from a single institution. Second, this survey was conducted in the form of a questionnaire only among postoperative patients with c-OPLL and did not include non-surgical control cases. In addition, the survey items were limited. It is possible that the RTW rate was calculated lower than the actual rate because it was not possible to confirm whether or not patients had the intention to return to work after surgery. Many patients undergoing surgery for c-OPLL are at the same age as the retirement age, and therefore may retire after surgery without wishing to return to work, regardless of the treatment outcome. In addition, it has also not been confirmed whether there is any workers’ compensation, which is shown to affect RTW after surgery. However, the RTW rate in this study was 76.3%, which is not low compared to cervical degenerative diseases other than c-OPLL, and even if these effects existed, they were thought to be limited. Third, in this multicenter study, surgical procedures were selected by each center and were not randomized, which may have had some influence on the association between surgical procedure and RTW. Finally, postoperative JOA score, preoperative JOACMEQ, and the presence or absence of perioperative complications were not investigated in this study. These investigations, if possible, would allow for a more detailed assessment and should be investigated in future studies.

In conclusion, this first nationwide multicenter study revealed that postoperative residual NeP was a significant independent factor associated with RTW after c-OPLL surgery. Our immediate challenge is to establish a treatment for postoperative residual pain, including NeP. The results of this study will provide useful information for determining future treatment plans for patients with a view to returning to work after c-OPLL surgery, and may also have an impact on the indications for surgery for this disease.

Patients and methods

Participants

This nationwide, multicenter study involved 13 academic institutions of the Japanese Multicenter Research Organization for Ossification of the Spinal Ligament (JOSL) formed by the Japanese Ministry of Health, Labour and Welfare and the Japanese Agency for Medical Research and Development (AMED). We conducted a questionnaire survey to investigate the status of RTW after surgery for c-OPLL. The protocol for this study has been approved by institutional review board (IRB) of Kitasato University as a Central IRB and the other all participating institutions including Shiga University of Medical Science as a local participating institution. This research was conducted in accordance with the “Declaration of Helsinki” and the Ministry of Health, Labor and Welfare / Ministry of Education, Culture, Sports, Science and Technology “Ethical Guidelines for Medical Research for Humans”. Informed consent was obtained from all subjects.

This study included patients who underwent surgical treatment for c-OPLL at participating institutions between 2014 and 2017 and were followed up for at least one year after surgery. A total of 286 patients (205 males and 81 females; average age 63.8 ± 10.7 years) who underwent surgery for myelopathy due to c-OPLL were enrolled from involved 13 institutions. Surgical procedures were selected by each participating institution and were not randomized. The surgical procedures performed were LMP, PDF, ADF, and AP combined. Patients who were unemployed before surgery were excluded from the study, but patients who were employed before surgery were not excluded because of age. Thus, 198 patients (160 males, 38 females, mean age at the time of surgery: 61.2 ± 10.8 years) with cervical myelopathy due to c-OPLL who were employed preoperatively were enrolled (Fig. 2).

Fig. 2.

Flowchart of study selection.

Occupations were classified into four categories: unemployed, light sedentary labor, light standing labor, and heavy labor, according to the previous study¹¹. Those who were able to return to work, regardless of whether they were in their original occupations or had changed occupations, were defined as having RTW. Employment style (full- or part-time employment), preoperative workload, and timing of RTW were also collected. Preoperative workload was assessed by the patients themselves as a percentage, with the state before the onset of symptoms being set at 100%. The patient demographics were collected from each patient, including age at the time of surgery, preoperative disease duration, gender, BMI, comorbidities, history of spine surgery of other sites.

Radiographical assessments

K-line, that is a straight line connecting the midpoints of the spinal canals of C2 and C7 in the lateral radiograph were determined on a lateral standard radiograph of the cervical spine in the neutral position²⁹. Patients were considered K-line—if OPLL crossed the K-line, and K-line + otherwise. The most compressed level and the presence of a signal intensity change in the spinal cord were investigated on T2-weighted MR imaging. In addition, COR of OPLL on axial computed tomography (CT) at the maximum cord compression level was investigated.

Clinical assessments

The preoperative clinical condition of the participants was determined using JOA score for cervical myelopathy³⁰. The JOA score is a tool used worldwide to assess function in cervical myelopathy, and assigns points based on assessments of motor function, sensory function, and bladder function, with a range of 0 (minimum) to 17 points (maximum). Postoperative JOACMEQ was used for patient-reported outcome measures (PROMs)³¹. JOACMEQ is a self-administered questionnaire consisting of 24 questions addressing five domains: cervical spine function (Q1), upper limb function (Q2), lower limb function (Q3), bladder function (Q4), and QOL (Q5). In JOACMEQ, pain or stiffness in neck or shoulders, tightness in chest, pain or numbness in arms or hands, and pain or numbness from chest to toe were evaluated by VAS. In the present study, we used the PDQ as PROMs to assess postoperative residual NeP³². The PDQ categorizes scores of 13–18 as “unclear” and scores of 19 or higher as “positive” for NeP. A classification of “uncertain” suggests that there is an equivocal but inclusive presence of NeP, whereas “positive” indicates a greater than 90% probability of NeP. In this study, according to previous reports²², a score of 13 or greater on the PDQ was defined as NeP.

Statistical analyses

To assess the statistical differences between the RTW + and RTW—groups, we used the t-test for continuous variables. In the JOACMEQ analysis, the Mann-Whiteny U test was used in accordance with the recommendation of the JOA. Fisher’s exact test was used for categorical variables. A P value below 0.05 was used as criterion for statistically significant difference. To elucidate the associated factors for success in achieving postoperative RTW, we employed multivariate logistic analysis. In the present study, we focused particularly on postoperative residual NeP and examined its influence using multivariate analysis, along with age, gender, and variables with significant univariate associations such as BMI, preoperative JOA score, and preoperative workload. Data in the present study are expressed as mean ± standard deviation. The Kaplan–Meier method was used to calculate the curves of the cumulative RTW rate. The software application used for the analysis was SPSS version 26.0 (SPSS Inc., Chicago, IL). Kaplan–Meier curve graph was created using the statistical software R (Version 4.5.0., R Foundation for Statistical Computing, Vienna, Austria).

Author contributions

K.M., M.M., Hir. N., H.T., S.Im., T.Y., M.K., and Y.K. contributed to planning and conduct of the present study and to reporting the present manuscript. K.M., K.S., K.K., S.M., T.H., M.M., S.Ik., M.K., S.Im. and M.Y. contributed to conception and design of the present study and to reporting the present study. S.Ik., Y.Y., K.S., T.E., M.T., S.T., S.K., S.E., T.H., S.M, T.H., N.N., Hir.N., Hid.N., K.K. contributed to conducting the present study and to editing the present manuscript. All authors reviewed the manuscript. All the authors read and approved the final manuscript. T.Y. supervised all the statistical analyses in the present study.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Competing interests

The authors declare no competing interests.

Institutional review board

This study was approved by each institutional review board.