Irreversibility of Nerve Root Sedimentation Sign in Lumbar Spinal Stenosis After Decompression Surgery: Incidence and Risk Factors


 Background. The nerve root sedimentation sign (Sed-sign) is a new diagnostic test for lumbar spinal stenosis. However, few studies have evaluated radiographical outcomes of positive Sed-sign after decompression surgery. The current study aims to evaluate the radiographicaland clinical outcomes of Sed-signafter decompression surgery among a relatively large sample sizeMethods. Patients with positive Sed-sign who underwent transforaminal lumbar interbody fusion (TLIF) surgery were reviewed. Based on postoperative MRI scans, patients with negative or irreversible Sed-sign were assigned to the reversible (R) or irreversible (Ir) groups, respectively. Demographics, radiographic parameters, and health-related quality of life (HRQOL) were evaluated.Results. The R and Ir groups were comprised of 67 and 15 patients, respectively. There were no significant differences between two groups in terms of mean age, sex, postoperative complications as well as mean follow-up time (all P>0.05). After surgery, disc height (DH), foramina height (FH), and segmental lordosis (SL) in both groups were restored. At the latest follow-up, the smallest cross-sectional area (CSA) was significantly increased when compared with preoperatively (P<0.05). The CSA value and correction rate in the R-group was considerably higher than in the Ir-group (P=0.002 and P=0.007). Both groups had improved HRQOL after TLIF surgery; however, the Oswestry disability index, Zürich Claudication Questionnaire, and visual analog scale for back and leg pain were higher in the Ir vs. R groups (P<0.05). Multiple logistic regression analysis revealed that a postoperative CSA less than 131.4 mm2 was a risk factor for the irreversibility of Sed-sign.Conclusion.TLIF surgery resulted in reversibility of positive Sed-sign for most patients. The irreversibility of Sed-sign was associated with poor clinical outcomes. Independent risk factor for the irreversibility of Sed-sign was CSA less than 131.4 mm2.


Background
Lumbar spinal stenosis (LSS) has become one of the most common reasons for spinal surgery in the aging population 1 . Success in surgery for these patients had mainly depended on an accurate diagnosis and decompression of central, lateral recess, and foraminal stenosis 2,3 . In past decades, the diagnosis of LSS has depended on radiological and clinical tests such as the cross-sectional area (CSA) of dural sac as well as walking distance 4,5 . Barz et al. 6 introduced a new morphological sign namely nerve root sedimentation sign (Sed-sign), which was de ned as presence of lumbar nerve roots oating in dural sac in at least 1 axial image. With the newly proposed Sed-sign, there has been an attempt to improve the identi cation of patients with clinically relevant central LSS 6 .
The incidence of positive Sed-sign was reported from 23-56% in a previous study [6][7][8] . By comparing surgical outcomes between patients showing positive and negative Sed-sign, Barz et al. 9 reported that the Sed-sign did not appear to predict better clinical outcomes. Whereas in non-surgically treated patients, a positive sign was found to be associated with more limited improvement 9 . Thus, surgery was proposed for patients with positive Sed-sign. Compared with the in uence of preoperative Sed-sign on postoperative surgical outcomes, only a limited number of studies have evaluated whether surgical decompression leads to reversal of the positive Sed-sign. Barz et al. 10 analyzed 30 patients with preoperative positive Sed-sign who underwent decompression surgery and found that 27 of them had negative Sed-sign at 3 months postoperative MRI evaluation. However, due to the limited sample size in their study, the in uence of the positive Sed-sign after surgery on patient-reported outcomes remains unknown. Further, it is essential to quantify the risk factors associated with the irreversible Sed-sign.
Hence, the current study aims to: (1) evaluate the radiographical outcomes of Sed-sign after decompression surgery among a relatively large sample size; (2) compare clinical outcomes between patients with postoperative negative and positive Sed-sign; and (3) further identify risk factors associated with the irreversible positive Sed-sign.

Subjects
This retrospective case series study was approved by our hospital's institutional review board. 223 patients who were identi ed with LSS at our hospital between January 2011 and December 2017 were identi ed. Inclusion criteria for this study included: (1) age 50-80 years; (2) central or combined LSS con rmed by radiologic examination on cross-sectional MRI; (3) diagnosis with preoperative Sed-sign; (4) undergoing single-level transforaminal lumbar interbody fusion (TLIF) surgery; and (5) MRI examination at 1-year post-operation. Any patient with one or more of the following criteria was excluded: (1) history of prior lumbar trauma, tumor, infection, and revision surgery; (2) patients with LSS at L5-S1 level; (3) concomitant lumbar scoliosis > 10º; and (4) incomplete demographic data and radiographs.
Each patient's demographic and clinical data, including age, sex, and diagnosis, were obtained using electronic medical records.

Surgical methods
Surgeries were performed by our single surgeon's team. All patients underwent continuous conservative treatment including medication and physical therapy for a minimum of 6 weeks before the surgery. After standard posterior exposure with subperiosteal dissection of the posterior elements, pedicle screws were placed. Then, adequate decompression was performed through the dominant side of the symptoms. After complete decompression and careful endplate preparation, temporary rod xations were placed bilaterally with a distraction of the disc space. After that, a polyetheretherketone cage, packed with a mixture of demineralized bone matrix and local bone, was positioned on the anterior rim of the vertebral body. Finally, permanent rods were bilaterally xed with proper bilateral compression to better restore lordosis.

Radiographic evaluation
MRI scans (T2-weighted transverse layers of 4 mm thickness; Siemens Symphony 1.5 T) were performed twice for each patient on 2 different days by 2 experienced independent operators. Using a picture archiving and communications system (PACS) with integrated digital area measurement (GE Healthcare), the smallest CSA of the dural sac was measured on 3 different MRI scans at surgical level by an experienced independent radiologist who was unaware of the Sed-sign as well as other additional clinical information. The mean value of the 3 measurements was calculated. The diagnosis of Sed-sign was based on the MRI scans at the pedicle level. A positive Sed-sign was de ned as the absence of nerve root sedimentation in at least 1 transverse MRI scan, at a level above or below, disregarding the location of the scan within the level and its proximity to the maximal stenosis 6 .
In addition to the previously mentioned parameters on MRI scans, the following parameters were measured on X-rays taken preoperatively and at 1-year postoperatively: (1) segmental lordosis (SL), the angle subtended by the superior endplate line of L4 and the inferior endplate line of L5; (2) disc height (DH), the mean value of the anterior and posterior margins of the intervertebral space; and (3) foramina height (FH), the distance between the inferior pedicle wall above the index disc space to the superior pedicle wall from the level below.
In this study, all radiographs were measured by two well-trained senior residents, and the mean of both measurements was adopted for analysis. The interobserver reproducibility of all measurements obtained was tested and quanti ed by the intraclass correlation coe cient (ICC). There were strong interobserver agreements for all parameters, as all ICCs exceeded 0.8.

Study group
Patients with preoperative positive Sed-sign and postoperative negative Sed-sign were assigned to the reversible group (R-group). The remaining patients with postoperative positive Sed-sign were assigned to the irreversible group (Ir-group).
Health-related quality of life (HRQOL) HRQOL was assessed using the Oswestry disability index scale (ODI), Zürich Claudication Questionnaire (ZCQ), and visual analog scale (VAS). All questionnaires were completed independently by the patients before surgery and at the latest follow-up.

Statistical analysis
All data were analyzed using SPSS software (version 20.0; USA). The statistical data are presented as mean ± standard deviation. The normally distributed data were compared between groups using an unpaired t test or Chi-square tests and within groups using a paired t test. Factors related to the irreversibility of Sed-sign were further investigated using multiple logistic regression analysis. P values < 0.05 were considered statistically signi cant.

Results
A total of 82 patients with mean age of 59.9 ± 10.2 years were enrolled. There were 12 patients who underwent TLIF at L2/3, 22 patients at L3/4, and 48 patients at L4/5, respectively. The average follow-up was 39.2 ± 12.7 months (range 26-49 months). Based on the MRI scans at the latest follow-up, 67 patients had negative Sed-sign, and were assigned to the R-group. The remaining 15 patients with positive Sed-sign were assigned to the Ir-group. The incidence of irreversibility of positive Sed-sign was 18.2%.
As summarized in Table 1, the characteristics of the R-group and the Ir-group did not differ statistically in terms of mean age, sex, postoperative complications, and follow-up time (all P > 0.05).

HRQOL Outcomes
The distribution of scores for HRQOL is shown in Table 3. There were no signi cant differences between the two groups in terms of preoperative ODI, ZCQ physical function and symptom severity domain, VASback, and leg pain. At the latest follow-up, both groups improved notably. However, the ODI, ZCQ physical function and symptom severity domain, VAS-back, and leg pain in the Ir-group were signi cantly higher than those in the R-group (P < 0.05).

Discussion
Since Sed-sign was rst introduced by Barz et al 6 , an important research focus has been on the evaluation of clinical and radiological characteristics to better distinguish LSS from lower back pain patients. Due to the relatively lower sensitivity in detecting clinically de ned LSS in orthopedic clinical cohorts, the Sed-sign does not allow for de nitive differential diagnosis of LSS 11,12 . Compared with nonsurgically treated positive Sed-sign patients, favorable outcomes have been reported for patients who underwent surgical treatment 9,13 . Therefore, Sed-sign seemed to be an indication to help determine the appropriate treatment. Previous studies investigating the Sed-sign have concentrated on the diagnosis of LSS as well as its in uence on the surgical outcomes. Evaluation of the reversibility of the Sed-sign after decompression surgery as well as the in uence of irreversibility on surgical outcomes is still mandatory.
The current study retrospectively reviewed 82 patients with LSS who underwent surgical decompression at our spine center. The incidence of positive Sed-sign in the current study was similar to that reported in the literature [6][7][8] . The de nitive disease mechanism for positive Sed-sign remains unknown. The increased epidural pressure at the level of spinal stenosis has been reported as the main cause for positive Sed-sign in patients with LSS 14 . Barz et al. 14 noted that increased epidural pressure at the level of the stenosis may result in tethering of nerve roots in the spinal canal at that level as if held by a mechanical clamp. In the current study, 80.4% of patients showed reversibility of the Sed-sign after decompression surgery performed at the level of stenosis. This tendency was similar to the study performed by Barz et al. 10 , who reported that 27 of 30 patients had negative Sed-sign after decompression surgery. Together, these results suggested that decompression surgery resulted in reversibility of Sed-sign in most patients. However, it should be noted that not all LSS patients with positive Sed-sign showed reversibility after decompression surgery (Fig. 1). The frequency of patients with positive Sed-sign after decompression surgery in the current study was slightly higher than the study of Barz et al. 10 This difference may be due to the fact that only patients who underwent single-level decompression surgery were enrolled in the current study.
Barz et al. 9 reported that a positive Sed-sign was associated with limited clinical improvement in nonsurgically treated patients. Among patients treated with decompression surgery, those with positive Sedsign achieved similar clinical improvements when compared with negative Sed-sign patients 9 . HRQOL in the current study, based on the ODI, VAS, and ZCQ scores, suggested that both R and Ir groups achieved improvements after surgery compared with the preoperative evaluations. This nding was consistent with those of Barz et al. 10 , who reported that patients with the irreversibility of Sed-sign made improvements in clinical outcomes for ODI, VAS, and ZCQ scores. In the current study, a further comparison between patients with positive and negative Sed-sign after decompression surgery showed that the ODI, VAS, and ZCQ scores in the Ir group were signi cantly lower than those in the R group. Our ndings suggested that the irreversibility of Sed-sign after decompression surgery was associated with poorer clinical outcomes when compared with those with negative Sed-sign at post-operation.
The main mechanisms underlying the irreversibility of positive Sed-sign remain unknown. Possible reasons for positive Sed-sign included insu cient decompression, postoperative hematoma, excessive postoperative scar tissue, and epidural lipomatosis 10 . Barz et al. 10 noted that the reasons for 3 patients with irreversibility of Sed-sign were potentially associated with postoperative complications, including two cases with epidural fat and one case with an epidural cyst. In fact, such complications may also be attributed to abnormal epidural pressure, like insu cient decompression of the LSS. In the current study, similar complication rates were found between those with reversibility and irreversibility of Sed-sign. Based on the multiple logistic regression, our results showed that the primary risk factor for the irreversibility of positive Sed-sign was a postoperative CSA of less than 131.4 mm 2 . The association between smaller CSA and the irreversibility of Sed-sign may also attribute to the increased epidural pressure, which may be induced by the relatively smaller CSA. Therefore, our results further demonstrated the relationship between increased epidural pressure and formation of positive Sed-sign.
The clinical relevance of this study relates to decreasing the incidence of the irreversibility of Sed-sign and improving HRQOL after decompression surgery. First, decompression at the stenosis level should be performed. Second, postoperative complications, such as epidural fat and hematoma, may also increase abnormal epidural pressure and further in uence the reversibility of preoperative Sed-sign. Therefore, complications should be identi ed and managed as soon as possible.
There were also some limitations in the current study. First, the sample size in the current study was relatively small. Patients enrolled in the current study only underwent single-level TLIF decompression for consistency. The relationship between multi-level decompression and reversibility of positive Sed-sign remains unclear. Second, HRQOL may be in uenced by several sagittal parameters. However, further evaluation of sagittal alignments, such as pelvic incidence-lumbar lordosis, was limited due to the retrospective character of the current study. Third, even all of these surgeries were performed by same surgical team and the goal of surgery is to achieve adequate decompression, the effect of insu cient decompression on HRQOL should not be neglected. Therefore, a larger sample size with a detailed evaluation of sagittal alignment should be performed in future studies.

Conclusions
Decompression surgery resulted in reversibility of positive Sed-sign for most patients. HRQOL in patients with negative Sed-sign was notably better than those with the irreversibility of Sed-sign. An independent risk factor for the irreversibility of Sed-sign was a CSA less than 131.4 mm 2 . This information should be taken into consideration during surgical decision making.