Relative risk factors of nerve root sedimentation sign (SedSign) in patients with severe central lumbar spinal stenosis (LSS)

Abstract

The incidence of nerve root sedimentation sign (SedSign) was evaluated to explore potential pathogenesis in patients with severe lumbar spinal stenosis (LSS). In a total of 209 patients with severe LSS, 290 intervertebral levels were narrow, among which 248 showed a positive SedSign, giving a prevalence of 85.52%. Those levels with a positive SedSign were further analyzed relative to those with a negative SedSign. There was no significant difference between the two groups for the cross-sectional area (CSA) or the posteroanterior diameter (PAD). In contrast, there was a significant difference between the groups for the grade of degenerative facet joint (DFJ) (p < 0.05), the thickness of ligamentum flavum (TLF) (p < 0.01), and the cross-sectional area difference (CSAD) (p < 0.01). In addition, receiver operating characteristic (ROC) curves were used to identify associated factors. The area under the ROC curve for PAD was 0.608 (p < 0.05), for DFJ was 0.634 (p < 0.05), for TLF was 0.74 (p < 0.01), and for CSAD was 0.911 (p < 0.01). In summary, a positive SedSign has notable advantages in assisting with the diagnosis of severe LSS. Compression of the dural sac from the rear may be the main risk factors of a positive SedSign.

KEYWORDS:

• Lumbar spinal stenosis (LSS)
• nerve root sedimentation sign (Sedsign)
• difference cross-sectional area difference (CSAD)
• thickness of ligamentum flavum (TLF)
• grade of degenerative facet joint (DFJ)

Introduction

Lumbar spinal stenosis (LSS) is represented by the reduction of the lumbar spinal canal capacity, compression of the dural sac, and entrapment of nerve roots, which collectively induce a series of clinical dysfunctions in the patient (Atlas et al. 2000; Verbiest 2001). Although patient history, clinical examination, electrophysiological analyses, and confirmatory imaging findings such as cross-sectional area (CSA) of the dural sac (Schizas et al. 2010; Hiyama et al. 2019) and posteroanterior diameter (PAD) of the spinal canal (Haig et al. 2007) can be used to diagnose LSS, there are currently no universally accepted diagnostic criteria for LSS (Fritz et al. 1997; Atlas et al. 2005; Kapural et al. 2007). Because diagnosis of LSS is difficult when clinical symptoms such as pain and functional limitations often occur only during activity but disappear at rest, imaging findings do not always correlate with clinical symptoms (Alyas et al. 2008; Arabmotlagh et al. 2019).

To improve the ability to diagnose LSS, Barz et al. (2010) introduced a new radiological index, the nerve root sedimentation sign (SedSign). The SedSign is a phenomenon visible in axial MRI scans: when a patient is in the supine position, an MRI scan shows that the lumbar nerve roots sediment, as a result of gravity, to the dorsal part of the dural sac in patients with no suspicion of LSS. In contrast, in patients with severe LSS, such sedimentation is almost always absent, this phenomenon being referred to as a positive sedimentation sign. According to the report from Barz et al., the SedSign is 94% sensitive and 100% specific for LSS, when used in conjunction with the criteria of walking distance ≤ 200 m and CSA of the dural sac ≤ 80 mm² to define probable LSS cases (Barz et al. 2010). Another research also showed that the sensitivity of the SedSign was 60–96% in postoperative spines (Tomkins-Lane et al. 2013). All these studies suggest that a positive SedSign is a sensitive MRI parameter of patients with LSS, especially patients with severe morphological spinal stenosis.

A SedSign measurement is simple, intuitive, and easy to obtain, and is considered a good indicator for the use of diagnosing severe LSS in clinical practice (Macedo et al. 2013; Zhang et al. 2015). However, the mechanism responsible for a positive SedSign is still not clear. What risk factors are related specifically to the phenomenon of a positive SedSign? We hypothesized that a positive SedSign is associated with a change in the dural sac at the level of intervertebral stenosis of patients with LSS. To test our hypothesis, we investigated the incidence of a positive SedSign and correlations with MRI parameters in patients with severe LSS.

Materials and methods

Participants

This study was a retrospective review, which was approved by the ethics committee of Qiqihar Medical College (reference number 201822). The MR images of patients with severe LSS were obtained from our hospital for individuals admitted for inpatient or outpatient treatment between January 2017 and June 2019, all of whom were consistent with LSS diagnostic criteria and were assessed for eligibility based on the following criteria: (1) a CSA of the dural sac of ≤80 mm² for at least one level in an axial MRI scan; (2) typical intermittent claudication, with or without lower back pain or leg pain; and (3) walking distance ≤ 500 m. The exclusion criteria were as follows: (1) presence of lower extremity arterial occlusive syndrome, lumbar tumor, multiple nerve injury, spinal trauma, or limited mobility caused by osteoarthritis; (2) presence of coronary thrombosis or a previous stent surgery; (3) LSS at level L5/S1 was excluded because the S1 and S2 nerve roots leave the dural sac in a ventral position, inhibiting sedimentation to the dorsal part of the dural sac according to Barz et al. (2010).

MRI data acquisition

A total of 627 patients who had undergone MRI examination of the lumbar spine were included in this study. MRI scans were made with a magnetic resonance instrument (HITACHI echelon 1.5 T, Japan) and consisted of sagittal T1- and T2-weighted images and axial T2-weighted images (thickness, 4 mm; 20% gap size). All patients were imaged while in the standard supine position, with both legs straight. The scanning range covered L1/2 to L5/S1, and the three scans described above were acquired for each intervertebral level. We used a complete digital image storage area measurement system (Accurad V4.0 software) to process the obtained data. All MRI parameters for each image scan were separately assessed by three radiologists who are experienced independent investigators. The mean value of the three calculations was used as the measurement for further analysis.

For each patient, the PAD of the spinal canal was measured in the three MRI scans of narrow levels as the distance between the midpoint of the posterior margin of the disc and the midpoint of the posterior wall of the spinal canal (Figure 1a). The minimum PAD was used for further investigation as it is indicative of the narrowing of the spinal canal in the sagittal plane. The thickness of the ligamentum flavum (TLF) was measured on axial T2-weighted MR images at the level of the facet joint as shown in Figure 1(b). The maximum TLF was determined as an indicator of dural sac posterior compression. In addition, the lumbar facet joints were graded on both the left and right side at levels L1/2, L2/3, L3/4, and L4/5, and then the average value was used to determine the degenerative facet joint (DFJ) grade. Four grades of DFJ were defined using criteria similar to those published by Kalichman et al. (2008) and Weishaupt et al. (1999); these criteria are shown in Table 1.

Figure 1. Measurement of the cross-sectional area (CSA) of the dural sac and the posteroanterior diameter (PAD) of the spinal canal. b: Measurement of the thickness of the ligamentum flavum (TLF) and the space of the facet joint (FJ) which can used to evaluate DFJ.

Table 1. Criteria for grading degeneration of the facet joint.

Grade	Criteria
0	Normal facet joint space (2 − 4 mm wide)
1	Narrowing of the joint space (<2 mm) and/or small osteophytes and/or mild hypertrophy of the articular process
2	Narrowing of the joint space (<1 mm) and/or moderate osteophytes and/or moderate hypertrophy of the articular process and/or mild subarticular bone erosions
3	Severe narrowing of the joint space and/or large osteophytes and/or severe hypertrophy of the articular process and/or severe subarticular bone erosions and/or subchondral cysts and/or vacuum phenomenon in the joints

Definition of the maximum cross-sectional area difference (CSAD)

The CSA of the dural sac was measured based on the area bounded by the edge of the epidural sac (Figure 1a) in each narrow intervertebral level of the three MRI scans to determine the minimum CSA, which represents the absolute compression of the dural sac. To describe the change in the dural sac, we introduced the maximum cross-sectional area difference (CSAD) of the dural sac, which was calculated by subtracting the minimum CSA measured across the three scans at each level where stenosis had occurred from the maximum CSA; the difference represents the CSAD value for that particular level. A higher CSAD value indicates a greater change in the dural sac at the level of narrowing. Conversely, a lower CSAD value indicates a more gradual narrowing of the dural sac under pressure.

Determining the nerve root SedSign

Patients were rated by the other three investigators as SedSign positive or negative based on their MR images. In brief, a vertical line was drawn along the midpoint of the posteroanterior diameter of the spinal canal, and a horizontal line was drawn that divided the dural sac into an upper and lower part in each axial T2-weighted image. A negative SedSign was defined as having all caudae equinae located in the lower part of the dural sac with the exception of the two ventral nerve roots that exit caudal to the level at which the observations were made (Figure 2a). A positive SedSign was defined as an absence of cauda equina sedimentation because of the tight canal, a result of the distortion of the dural sac, with the majority of nerve roots located in the upper part of the sac (Figure 2b). Where there was a disagreement between the raters, a consensus was reached between both investigators, who were assisted by another experienced independent investigator as a third opinion. All imaged levels for each individual were classified as having a positive or negative SedSign.

Figure 2. A negative SedSign was defined as having all caudae equinae located in the lower part of the horizontal red dashed line with the exception of the two ventral nerve roots that exit caudal to the level at which the image was taken. b: A positive SedSign was defined as an absence of cauda equina sedimentation, and a ‘squashing’ of the dural sac, with the majority of nerve roots located above the horizontal red dashed line. The horizontal dashed line passes through the midpoint of the posteroanterior diameter of the spinal canal (the red solid line).

Statistical analysis

Data are shown as the mean ± standard deviation. The t-test was applied for comparisons between the positive SedSign group and the negative group. The receiver operating characteristic (ROC) curve was used to assess correlations between morbidity of positive SedSign and parameters such as the minimum CSA, minimum PAD, maximum TLF, grade of DFJ, and maximum CSAD. SPSS18.0 software was used for all statistical analyses, and p < 0.05 was considered as statistically significant.

Results

According to the inclusion/exclusion criteria, 209 patients were included in the current study, and their general information was shown in Table 2. There were 84 males and 125 females, aged 57.3 ± 14.9 and 62.68 ± 11.06 years, respectively. There was no significant difference in Oswestry Disability Index (ODI) and walking distance between male and female patients, but a significant difference in BMI was found. Among these patients, 290 intervertebral levels were identified as having severe LSS, which included 248 intervertebral levels with a positive SedSign and 42 levels with a negative SedSign. The occurrence of positive and negative SedSign measurements at different intervertebral levels for the 290 levels with severe LSS is shown in Table 3. The prevalence of a positive SedSign was 85.52% for all levels.

Table 2. The general information of 209 patients with severe LSS.

	Cases	Age	BMI	ODI	Claudication distance
Male	84	65.3 ± 12.32	27.83 ± 2.05*	65.36 ± 15.29	220 ± 164.2
Female	125	63.74 ± 13.66	24.68 ± 1.96	63.95 ± 13.26	239.7 ± 198.1

*p < 0.05.

Table 3. Distribution of a positive SedSign across 290 levels of LSS.

Distribution	Levels of LSS	SedSign (positive)	SedSign (negative)	Morbidity
L1/2 level	2	2	0	100%
L2/3 level	12	12	0	100%
L3/4 level	87	76	11	87.36%
L4/5 level	189	158	31	83.60%
Total	290	248	42	85.52%

We then compared several parameters, including minimum PAD and CSA, DFJ, maximum TLF and CSAD, between the levels with a positive SedSign (n = 248) and those with a negative SedSign (n = 42), and the results are shown in Figure 3. Between the positive and negative SedSign groups, there was no significant difference with respect to the minimum PAD and CSA (p > 0.05). However, there was a significant difference in the maximum TLF and the grade of DFJ, and the maximum CSAD (p < 0.05).

Figure 3. The MRI parameters were evaluated between the positive SedSign group and the negative SedSign group. a: The minimum CSA. b: The minimum PAD. c: The maximum TLF. d: The grade of DFJ. e: The maximum CSAD. *p < 0.05 and **p < 0.01.

To evaluate any correlations between a positive SedSign and the above parameters, we further studied the sensitivity between the prevalence of a positive SedSign and these parameters with the ROC curve method (Figure 4). Our results suggested that there is no obvious correlation between the prevalence of a positive SedSign and minimum CSA (p > 0.05). However, the prevalence was moderately correlated with minimum PAD and DFJ (p < 0.05). Finally, significant correlation was observed between the prevalence of a positive SedSign and the maximum TLF and CSAD (p < 0.01).

Figure 4. Correlation between the prevalence of a positive SedSign and grade of DF, maximum TLF and CSAD, minimum CSA and PAD. The area under the ROC curve (AUC) for the grade of DFJ was 0.634 (a line, 95% CI: 0.576 − 0.69, p < 0.05). The AUC for maximum CSAD was 0.913 (b line, 95% CI: 0.875 − 0.943, p < 0.01). The AUC for maximum TLF were 0.793 (c line, 95% CI: 0.742 − 0.839, p < 0.01). The AUC for minimum CSA was 0.543 (d line, 95% CI: 0.484 − 0.601, p > 0.05). The AUC for minimum PAD was 0.608 (e line, 95% CI: 0.55 − 0.665, p < 0.05).

Discussion

Here we conducted a retrospective study to evaluate the lumbar MR images of 209 patients with severe LSS, including 84 male and 125 female patients. We found no significant difference in average age and ODI, and in particular, no significant difference could be found in walking distance, between male and female with severe LSS. However, we found a significant difference in BMI between the two, which may be due to gender differences between male and female. In total, 290 lumbar sections were diagnosed as severe LSS based on our inclusion criteria, and 248 intervertebral discs were assigned to the positive SedSign group. There were only 2 sections at the L1/2 level and 12 at the L2/3 level diagnosed as severe LSS, all of which were assessed as having positive SedSign (100%). Meanwhile, the incidence of a positive SedSign was 76 in 87 L3/4 levels (87.36%) and 158 in 189 L4/5 levels (83.6%). Therefore, the overall incidence of a positive SedSign was 85.52% in this study. Our results suggested a positive SedSign was most common in the lower lumbar spine, which is consistent with the segments that show a high incidence of LSS (Binder et al. 2002; Wu and Cruz 2020). Thus, our results suggested that a positive SedSign should be used as an image parameter for the diagnosis of and screening for LSS in clinical practice.

Although the SedSign has been reported to have high diagnostic sensitivity, specificity, and efficacy, and good clinical application value for the diagnosis of LSS (Barz et al. 2010; Macedo et al. 2013; Tomkins-Lane et al. 2013; Zhang et al. 2015), the pathogenesis and correlated risk factors of positive SedSign were still unclear. As well known, the PAD of spinal canal, as a linear indicator of the spinal canal, is measured as the distance from the midpoint of the anterior wall to the midpoint of the posterior wall, and was used to assess the degree of spinal stenosis in the sagittal plane (Sheldom et al. 1976). In the present study, we found that there was no significant difference in the PAD between the positive and negative SedSign groups, although the ROC curve for the PAD showed a mid-correlation between a positive SedSign and the PAD. We considered that the main reason may be the physiologically invalid cavity filled with adipose tissue existing between the posterior of the dural sac and the posterior wall of the spinal canal, which may affect the PAD of the spinal canal to reflect the degree of spinal canal stenosis effectively. In addition, the CSA of the dural sac, as the spinal canal area parameter, was superior to vertebral canal diameter line parameters in diagnosing LSS (Hamanishi et al. 1994). Due to the characteristics of the spinal canal morphology, some degenerative changes occur in the non-midline part of the spinal canal, often inducing lateral recess stenosis and finally lead to reduction in spinal canal volume (Hamanishi et al. 1994). However, some researchers considered that the CSA could be insufficient as a diagnostic tool (Staub et al. 2011; Piechota et al. 2019). Lohman et al. (2006) confirmed that the degree of LSS and the CSA of the dural sac had no significant correlation with the severity of clinical symptoms. Our results also showed that the minimum CSA was not significantly different between the positive SedSign group and the negative SedSign group; at the same time, the ROC curve also showed that there was no significant correlation between the prevalence of a positive SedSign and the minimum CSA. Thus, it is also believed that the CSA of the dural sac and PAD of the spinal canal cannot fully explain the involvement of nerves in LSS due to the great individual differences.

To further investigate the possible pathogenesis that leads to a positive SedSign, we conducted a novel radiological parameter, the maximum CSAD of the dural sac, to describe the narrowing change of the dural sac. In the present study, we observed the sagittal and axial MR images of the patients with severe LSS who were determined as having a positive SedSign at the L4/5 level (Figure 5). The dural sac was pushed ventrally or toward the center of the spinal canal by posterior compression in the region where the most severe narrowing occurred (Figure 5c), and the CSA was at its minimum in this scan image. However, the dural sac at the adjacent sites was less compressed, as shown in Figure 5(b), and the corresponding CSA was more normal. The maximum CSAD of the dural sac was large, which indicated an acute change in the dural sac between the narrowest section and the normal section. As a result, the nerve roots were pulled toward the center of the spinal canal and a positive SedSign was observed on the MR image. In contrast, when the maximum CSAD was small, there was only minor variation in the dural sac between the level at which narrowing occurred and normal levels, resulting in minimal displacement of the nerve roots and the absence of a positive SedSign in the MR image at the levels adjacent to the stenosis. Meanwhile, significant differences also were observed in the maximum CSAD between the positive group and the negative group, and the ROC curve result also showed that there was the highest correlation between the maximum CSAD and incidence rate of positive SedSign. All these results suggested that the positive SedSign is more closely related to a change in the dural sac caused by posterior compression at the level of stenosis, which may be the main reason for the appearance of sedimentation syndrome.

Figure 5. The relationship between a positive SedSign and a change in the CSA of the dural sac at the level of stenosis. a: A sagittal T2-weighted image of L4/5 shows compression of the dural sac because of substantial narrowing in the third MRI scan. b: The first transverse layer of level L4/5, at which point the dural sac was lightly compressed, and there was minimal tendency of the neve roots or cauda equina to move ventrally or toward the center of the spinal canal. A suggestion of a positive SedSign was observed, although not definitively. c: The second transverse layer of level L4/5 OR MR image, at which point the narrowing of the dural sac was increased, the nerve roots were shifted substantially, and a positive SedSign was present. d: The third transverse layer of level L4/5 showed the greatest stenosis. Because of the narrowing of the canal, the nerves were ‘‘squashed’’ and therefore present on both sides of the equator, such that a positive SedSign was apparent.

To verify the hypothesis, two posterolateral parameters, thickness of ligamentum flavum (TLF) and degeneration of facet joint (DFJ), were further assessed as to their correlation with the positive SedSign. The ligamentum flavum and facet joint are the main structures that make up the posterior and lateral spinal canal walls, and have a protective effect on the spinal cord (Karavelioglu et al. 2016). They have been confirmed to have important roles in the development of LSS (Fukuyama et al. 1995; Sakamaki et al. 2009; Zhang et al. 2010). TLF and DFJ can induce a decrease in the central tube volume by compression from the behind the dural sac, which is the cause of LSS (Wessberg and Frennered 2017; An et al. 2018; Nakashima et al. 2019). Therefore, we analyzed the TLF and DFJ between the two groups and found a significant difference for each of these parameters between the positive and negative groups. In addition, The ROC curve result also showed that a positive SedSign was significantly correlated with the grade of DFJ and the TLF. All these demonstrated that a positive SedSign was highly related to risk factors from the posterior spinal canal. This would also explain why there is a different prevalence of a positive SedSign between cases of severe LSS and moderate/mild LSS. The change of compressed dural sac was less in patients with mild-to-moderate LSS, and for whom the MR images rarely show a positive SedSign. However, when the dural sac (nerve roots or the cauda equina) was obviously squeezed from the posterior side and moved sharply toward the center of the spinal canal or ventrally at the level where stenosis occurred, the adjacent unaffected O nerve roots (or the cauda equina) were also pulled to shift to the center of the spinal canal or ventrally, and a positive SedSign was observed in MR images. Barz et al. (2014) reported that a positive SedSign was more common when the epidural pressure was increased in LSS patients, which also indirectly supports our results.

Of course, as LSS develops from complex pathophysiological changes, there are many factors that can decrease the volume of the spinal canal, such as lumbar kyphosis (Jung et al. 2018; Park et al. 2018), loss of physiological lordosis (Celestre 2018), giant central lumbar disc herniation (Ammar et al. 2018; Tulloch and Papadopoulos 2018), and lateral recess stenosis (Raja et al. 2020), and can result in typical clinical symptoms of LSS. Not all LSS cases will show a positive SedSign, which suggests that there are limitations of SedSign determination in clinical practice. In addition, in the current study, we focused only on the distribution of SedSign in patients with severe LSS. The validity of this theory on a wider scale is not currently known. Further study is needed to determine the distribution of a positive SedSign among patients with mild-to-moderate LSS.

Conclusion

In summary, the incidence of a positive SedSign was 85.52% among 290 levels with spinal canal narrowing in 209 patients with severe LSS in this study. The results show that a positive SedSign can be used as a parameter to assist with the diagnosis of severe LSS, along with other criteria. The prevalence of a positive SedSign showed a higher correlation with changes in the compression of the dural sac relative to other imaging parameters. Compression from the posterior spinal canal, such as thickening of the ligamentum flavum and facet joint degeneration, may be the main cause of a positive SedSign.

Author contributions statement

Conception and design of the research: Nan ZHANG and Yunfeng HAN; acquisition of data: Haiming YU, Rui ZHANG, Chu SUN, and Bo YUE; analysis and interpretation of data: Haiming YU, Rui ZHANG, Chu SUN, Bo YUE, Mingda WANG, Kaiping CHOU, and Bin LI; statistical analysis: Yunfeng HAN; drafting the manuscript: Haiming YU; revision of manuscript for important intellectual content: Nan ZHANG. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available in https://data.mendeley.com/datasets/w5p4n7rhwy/1.

Additional information

Funding

This work was financially supported by the Doctoral Research Funding of Qiqihar Medical College (QMSI201901) and Clinical Research Project of Heilongjiang Health Commission (2019-026).