Comparison of Patients Operated for Lumbar Spinal Stenosis with and without Spondylolisthesis - A Secondary Analysis of the NORDSTEN Trials.

STUDY DESIGN: Observational cohort study (secondary analysis of two randomized trials). OBJECTIVE: To investigate whether function, disability, pain and quality of life before surgery and patient-reported outcome as well as complication and reoperation rates up to two years after surgery differ between lumbar spinal stenosis patients with and without spondylolisthesis. SUMMARY OF BACKGROUND DATA: Lumbar spinal stenosis is a degenerative condition of the spine, which appears with or without degenerative spondylolisthesis often presenting similar signs and symptoms. METHOD: This study is a secondary analysis of two randomized trials on patients with lumbar spinal stenosis with and without spondylolisthesis conducted at 16 public Norwegian hospitals. Disability, function, back pain, leg pain, quality of life, complication and reoperation rates up to two years after surgery were compared between the two cohorts. RESULTS: A total of 704 patients were included in this study, 267 patients with spondylolisthesis (median age 67.0 years [IQR 61.0-72.0]; 68.7% female) and 437 patients without spondylolisthesis (median age 68.0 years IQR 62.0-73.0]; 52.9% female). In the linear mixed model analysis there were no significant differences in disability, function, back pain, leg pain and quality of life scores between the two cohorts of patient with and without spondylolisthesis before surgery or at two years follow-up. The complication rate was 22.9% in patients with spondylolisthesis and 12.1% in patients without spondylolisthesis (P<0.001). There were no significant differences in reoperation rates. CONCLUSION: In patients with lumbar spinal stenosis the symptom burden before surgery and the clinical outcome up to two years after surgery were similar independently of a concomitant spondylolisthesis.

Change in Lumbar Lordosis after Decompressive Surgery in Lumbar Spinal Stenosis Patients and Associations with Patient Related Outcomes 2 Years after Surgery. Radiological and Clinical Results from the NORDSTEN Spinal Stenosis Trial.

STUDY DESIGN: A prospective cohort study. OBJECTIVE: The aim was to investigate changes in lumbar lordosis (LL) and its association to changes in patient reported outcome measures (PROMs) after decompressive surgery for lumbar spinal stenosis (LSS). SUMMARY OF BACKGROUND: Few studies have addressed change in LL after decompression surgery for LSS in relation to outcomes. METHOD: Pre- and postoperative data from 310 patients having standing x-ray both before and 2 years after surgery were included. The patients were grouped based on the change in LL preoperatively to 2 years after surgery; group 1: <5 degrees (n=196), group 2: ≥5 <10 degrees (n=55) or group 3: ≥10 degrees (n=59) of change in LL. The changes in function, disability and pain were assessed by the Oswestry Disability Index (ODI), Numeric Rating Scale (NRS), and the Zurich claudication questionnaire (ZCQ). The three groups were compared regarding baseline variables using the ANOVA test for continuous variables and the chi-square test for categorical variables. The groups were further compared with a likelihood ratio test in relation to changes in PROMs 2 year after surgery and outcomes were adjusted for respective baseline PROMs, age, sex, smoking, BMI, Schizas and Pfirrmann scores. RESULTS: LL was significantly changed at group level 2 years after surgery with a mean difference of 2.2 (SD 9.4) degrees ( P =0.001). The three LL change groups did not show any significant differences in patient characteristics, function, disability, and pain at baseline. The two groups with a change of more than 5 degrees in LL 2 year after surgery (group 2 and 3) had significantly greater improvements in ODI ( P =0.022) and ZCQ function ( P =0.016) in the adjusted analyses, but was not significant for back and leg pain. CONCLUSION: Changed LL after decompressive surgery for LSS was associated with improved ODI and physical function.

Bacterial growth in patients with low back pain and Modic changes: protocol of a multicentre, case-control biopsy study.

INTRODUCTION: Bacterial infection and Modic changes (MCs) as causes of low back pain (LBP) are debated. Results diverged between two randomised controlled trials examining the effect of amoxicillin with and without clavulanic acid versus placebo on patients with chronic LBP (cLBP) and MCs. Previous biopsy studies have been criticised with regard to methods, few patients and controls, and insufficient measures to minimise perioperative contamination. In this study, we minimise contamination risk, include a control group and optimise statistical power. The main aim is to compare bacterial growth between patients with and without MCs. METHODS AND ANALYSIS: This multicentre, case-control study examines disc and vertebral body biopsies of patients with cLBP. Cases have MCs at the level of tissue sampling, controls do not. Previously operated patients are included as a subgroup. Tissue is sampled before antibiotic prophylaxis with separate instruments. We will apply microbiological methods and histology on biopsies, and predefine criteria for significant bacterial growth, possible contamination and no growth. Microbiologists, surgeons and pathologist are blinded to allocation of case or control. Primary analysis assesses significant growth in MC1 versus controls and MC2 versus controls separately. Bacterial disc growth in previously operated patients, patients with large MCs and growth from the vertebral body in the fusion group are all considered exploratory analyses. ETHICS AND DISSEMINATION: The Regional Committees for Medical and Health Research Ethics in Norway (REC South East, reference number 2015/697) has approved the study. Study participation requires written informed consent. The study is registered at ClinicalTrials.gov (NCT03406624). Results will be disseminated in peer-reviewed journals, scientific conferences and patient fora. TRIAL REGISTRATION NUMBER: NCT03406624.

Dural Sac Cross-sectional area change from preoperatively and up to 2 years after decompressive surgery for central lumbar spinal stenosis: investigation of operated levels, data from the NORDSTEN study.

PURPOSE: The aim of the present study was to investigate how canal area size changed from before surgery and up to 2 years after decompressive lumbar surgery lumbar spinal stenosis. Further, to investigate if an area change postoperatively (between 3 months to 2 years) was associated with any preoperative demographic, clinical or MRI variables or surgical method used. METHODS: The present study is analysis of data from the NORDSTEN- SST trial where 437 patients were randomized to one of three mini-invasive surgical methods for lumbar spinal stenosis. The patients underwent MRI examination of the lumbar spine before surgery, and 3 and 24 months after surgery. For all operated segments the dural sac cross-sectional area (DSCA) was measured in mm2. Baseline factors collected included age, gender, BMI and smoking habits. Furthermore, surgical method, index level, number of levels operated, all levels operated on and baseline Schizas grade were also included in the analysis. RESULTS: 437 patients were enrolled in the NORDSTEN-SST trial, whereof 310 (71%) had MRI at 3 months and 2 years. Mean DSCA at index level was 52.0 mm2 (SD 21.2) at baseline, at 3 months it increased to 117.2 mm2 (SD 43.0) and after 2 years the area was 127.7 mm2 (SD 52.5). Surgical method, level operated on or Schizas did not influence change in DSCA from 3 to 24 months follow-up. CONCLUSION: The spinal canal area after lumbar decompressive surgery for lumbar spinal stenosis increased from baseline to 3 months after surgery and remained thereafter unchanged 2 years postoperatively.

Preoperative fatty infiltration of paraspinal muscles assessed by MRI is associated with less improvement of leg pain 2 years after surgery for lumbar spinal stenosis.

PURPOSE: Fatty infiltration (FI) of the paraspinal muscles may associate with pain and surgical complications in patients with lumbar spinal stenosis (LSS). We evaluated the prognostic influence of MRI-assessed paraspinal muscles' FI on pain or disability 2 years after surgery for LSS. METHODS: A muscle fat index (MFI) was calculated (by dividing signal intensity of psoas to multifidus and erector spinae) on preoperative axial T2-weighted MRI of patients with LSS. Pain and disability 2 years after surgery were assessed using the Oswestry disability index, the Zurich claudication questionnaire and numeric rating scales for leg and back pain. Multivariate linear and logistic regression analyses (adjusted for preoperative outcome scores, age, body mass index, sex, smoking status, grade of spinal stenosis, disc degeneration and facet joint osteoarthritis) were used to assess the associations between MFI and patient-reported clinical outcomes. In the logistic regression models, odds ratios (OR) and 95% confidence intervals (CI) were calculated for associations between the MFI and ≥ 30% improvement of the outcomes (dichotomised into yes/no). RESULTS: A total of 243 patients were evaluated (mean age 66.6 ± 8.5 years), 49% females (119). Preoperative MFI and postoperative leg pain were significantly associated, both with leg pain as continuous (coefficient - 3.20, 95% CI - 5.61, - 0.80) and dichotomised (OR 1.51, 95% CI 1.17, 1.95) scores. Associations between the MFI and the other outcome measures were not statistically significant. CONCLUSION: Preoperative FI of the paraspinal muscles on MRI showed statistically significant association with postoperative NRS leg pain but not with ODI or ZCQ.

The association between lumbar lordosis preoperatively and changes in PROMs for lumbar spinal stenosis patients 2 years after spinal surgery: radiological and clinical results from the NORDSTEN-spinal stenosis trial.

BACKGROUND: Patients with lumbar spinal stenosis (LSS) sometimes have lower lumbar lordosis (LL), and the incidence of LSS correlates closely with the loss of LL. The few studies that have evaluated the association between LL and clinical outcomes after non-instrumented surgery for LSS show conflicting results. This study investigates the association between preoperative LL and changes in PROMs 2 years after decompressive surgery. METHOD: This prospective cohort study obtained preoperative and postoperative data for 401 patients from the multicenter randomized controlled spinal stenosis trial as part of the NORwegian degenerative spondylolisthesis and spinal STENosis (NORDSTEN) study. Before surgery, the radiological sagittal alignment parameter LL was measured using standing X-rays. The association between LL and 2-year postoperative changes was analyzed using the oswestry disability index (ODI), a numeric rating scale (NRS) for low back and leg pain, the Zurich claudication questionnaire (ZCQ), and the global perceived effect (GPE) score. The changes in PROMs 2 years after surgery for quintiles of lumbar lordosis were adjusted for the respective baseline PROMs: age, sex, smoking, and BMI. The Schizas index and the Pfirrmann index were used to analyze multiple regressions for changes in PROMs. RESULTS: There were no associations in the adjusted and unadjusted analyses between preoperative LL and changes in ODI, ZCQ, GPE, and NRS for back and leg pain 2 years after surgery. CONCLUSION: LL before surgery was not associated with changes in PROMs 2 years after surgery. Lumbar lordosis should not be a factor when considering decompressive surgery for LSS.

Machine Learning Models for Predicting Disability and Pain Following Lumbar Disc Herniation Surgery.

Importance: Lumber disc herniation surgery can reduce pain and disability. However, a sizable minority of individuals experience minimal benefit, necessitating the development of accurate prediction models. Objective: To develop and validate prediction models for disability and pain 12 months after lumbar disc herniation surgery. Design, Setting, and Participants: A prospective, multicenter, registry-based prognostic study was conducted on a cohort of individuals undergoing lumbar disc herniation surgery from January 1, 2007, to May 31, 2021. Patients in the Norwegian Registry for Spine Surgery from all public and private hospitals in Norway performing spine surgery were included. Data analysis was performed from January to June 2023. Exposures: Microdiscectomy or open discectomy. Main Outcomes and Measures: Treatment success at 12 months, defined as improvement in Oswestry Disability Index (ODI) of 22 points or more; Numeric Rating Scale (NRS) back pain improvement of 2 or more points, and NRS leg pain improvement of 4 or more points. Machine learning models were trained for model development and internal-external cross-validation applied over geographic regions to validate the models. Model performance was assessed through discrimination (C statistic) and calibration (slope and intercept). Results: Analysis included 22 707 surgical cases (21 161 patients) (ODI model) (mean [SD] age, 47.0 [14.0] years; 12 952 [57.0%] males). Treatment nonsuccess was experienced by 33% (ODI), 27% (NRS back pain), and 31% (NRS leg pain) of the patients. In internal-external cross-validation, the selected machine learning models showed consistent discrimination and calibration across all 5 regions. The C statistic ranged from 0.81 to 0.84 (pooled random-effects meta-analysis estimate, 0.82; 95% CI, 0.81-0.84) for the ODI model. Calibration slopes (point estimates, 0.94-1.03; pooled estimate, 0.99; 95% CI, 0.93-1.06) and calibration intercepts (point estimates, -0.05 to 0.11; pooled estimate, 0.01; 95% CI, -0.07 to 0.10) were also consistent across regions. For NRS back pain, the C statistic ranged from 0.75 to 0.80 (pooled estimate, 0.77; 95% CI, 0.75-0.79); for NRS leg pain, the C statistic ranged from 0.74 to 0.77 (pooled estimate, 0.75; 95% CI, 0.74-0.76). Only minor heterogeneity was found in calibration slopes and intercepts. Conclusion: The findings of this study suggest that the models developed can inform patients and clinicians about individual prognosis and aid in surgical decision-making.

Do patients with lumbar spinal stenosis benefit from decompression of levels with adjacent moderate stenosis? A prospective cohort study from the NORDSTEN study.

BACKGROUND: Lumbar spinal stenosis (LSS) is characterized by pain that radiates to the buttocks and/or legs, aggravated by walking and relieved by forward flexion. There is poor correlation between clinical symptoms and severity of stenosis on MRI, and multilevel stenosis has not been described to present worse symptoms or treatment outcomes, compared with patients with single-level stenosis. In patients with one level with severe stenosis combined with an adjacent level with moderate stenosis, the surgeon must decide whether to decompress only the narrowest level or both, to achieve the best possible outcome. The potential benefits of performing surgery on an adjacent moderate stenosis is debated, and the scientific evidence in scarce. PURPOSE: The aim of the present study was to investigate whether patients with a level of adjacent moderate stenosis, along with an index stenosis, benefitted from a dual-level decompression (DLD) compared with a single-level decompression (SLD). Furthermore, to investigate whether DLD patients had longer duration of surgery and hospital stay, higher rates of complications and/or lower rate of reoperations compared with SLD patients. STUDY DESIGN: Prospective cohort study. PATIENT SAMPLE: We analyzed data from the Norwegian Degenerative Spondylisthesis and Spinal Stenosis study- Spinal Stenosis Trial (NORDSTEN-SST). In this randomized multicenter study, 437 patients were included, evaluating clinical outcomes of three different surgical treatment options for LSS. Patients with degenerative spondylolisthesis were excluded. METHOD: Based on preoperative MRI, the present analysis included all patients who had a moderate stenosis (defined as Schizas B or C) in addition to a predefined index stenosis (the level with the smallest cross-sectional area). We compared patients who, based on the surgeons` choice, received a dual-level decompression, with those receiving a single-level decompression. OUTCOME MEASURES: The primary outcome was mean change in the Oswestry Disability Index (ODI) score from baseline to 2-year follow up. Secondary outcomes were proportion of success (30% reduction in ODI score), the Numeric Rating Scales for back and leg pain (NRS), the EuroQol 5-dimensional questionnaire utility index (EQ-5D), the Zurich Claudication Questionnaire (ZCQ), the Global Perceived Effect (GPE)-scale, duration of surgery, duration of hospital stay, perioperative complications and reoperation rates. RESULTS: Among the 222 patients, included in the analysis, 108 underwent DLD and 114 underwent SLD. There was no difference in change scores for any of the investigated patient-reported outcomes between the groups after 2 years. However, the DLD group had longer duration of surgery and longer length of hospital stay. There was no difference in reoperation rates or perioperative complications. CONCLUSION: This study, alongside the NORDSTEN-LSS trial on patients with adjacent moderate stenosis as well as an index stenosis, showed no superior clinical effectiveness for dual-level surgery compared with single-level surgery.

Longitudinal Relationship Between Reduced Modic Change Edema and Disability and Pain in Patients With Chronic Low Back Pain.

STUDY DESIGN: Secondary analyses of a randomized trial [Antibiotics In Modic changes (MCs) study]. OBJECTIVE: To assess whether or not reduced MC edema over time is related to reduced disability and pain in patients with chronic low back pain (LBP). SUMMARY OF BACKGROUND DATA: It is not clear whether or not reduced MC edema implies improved clinical outcomes. PATIENTS AND METHODS: Linear regression was conducted separately in 2 subgroups with MC edema at baseline on short tau inversion recovery (STIR) or T1/T2-weighted magnetic resonance imaging, respectively. Independent variable: reduced edema (yes/no) at 1 year on STIR or T1/T2-series, respectively. Dependent variable: 1-year score on the Roland-Morris Disability Questionnaire (RMDQ), Oswestry Disability Index (ODI), or 0 to 10 numeric rating scale for LBP intensity, adjusted for the baseline score, age, smoking, body mass index, physical workload, and baseline edema on STIR (STIR analysis only). Post hoc, we, in addition, adjusted all analyses for baseline edema on STIR, treatment group (amoxicillin/placebo), and prior disc surgery-or for disc degeneration. RESULTS: Among patients with MC edema on STIR at baseline (n = 162), reduced edema on STIR was not significantly related to the RMDQ ( B : -1.0, 95% CI: -2.8, 0.8; P = 0.27), ODI ( B :-1.4, 95% CI: -5.4, 2.6; P = 0.50), or LBP intensity scores ( B : -0.05, 95% CI: -0.8, 0.7; P = 0.90) after 1 year. Among patients with MC edema on T1/T2-series at baseline (n = 116), reduced edema on T1/T2 ( i.e ., reduced volume of the type 1 part of MCs) was not significantly related to RMDQ ( B: -1.7, 95% CI: -3.8, 0.3; P = 0.10) or ODI score ( B : -2.3, 95% CI: -7.1, 2.5; P = 0.34) but was significantly related to LBP intensity at 1 year ( B : -0.9, 95% CI: -1.8, -0.04; P = 0.04; correlation coefficient: 0.24). The post hoc analyses supported these results. CONCLUSION: Reduced MC edema over 1 year was not significantly associated with pain-related disability but was (on T1/T2-series) significantly but weakly related to reduced LBP intensity. LEVEL OF EVIDENCE: Level 3.

The Norwegian degenerative spondylolisthesis and spinal stenosis (NORDSTEN) study: study overview, organization structure and study population.

PURPOSE: To provide an overview of the The Norwegian Degenerative spondylolisthesis and spinal stenosis (NORDSTEN)-study and the organizational structure, and to evaluate the study population. METHODS: The NORDSTEN is a multicentre study with 10 year follow-up, conducted at 18 public hospitals. NORDSTEN includes three studies: (1) The randomized spinal stenosis trial comparing the impact of three different decompression techniques; (2) the randomized degenerative spondylolisthesis trial investigating whether decompression surgery alone is as good as decompression with instrumented fusion; (3) the observational cohort tracking the natural course of LSS in patients without planned surgical treatment. A range of clinical and radiological data are collected at defined time points. To administer, guide, monitor and assist the surgical units and the researchers involved, the NORDSTEN national project organization was established. Corresponding clinical data from the Norwegian Registry for Spine Surgery (NORspine) were used to assess if the randomized NORDSTEN-population at baseline was representative for LSS patients treated in routine surgical practice. RESULTS: A total of 988 LSS patients with or without spondylolistheses were included from 2014 to 2018. The clinical trials did not find any difference in the efficacy of the surgical methods evaluated. The NORDSTEN patients were similar to those being consecutively operated at the same hospitals and reported to the NORspine during the same time period. CONCLUSION: The NORDSTEN study provides opportunity to investigate clinical course of LSS with or without surgical interventions. The NORDSTEN-study population were similar to LSS patients treated in routine surgical practice, supporting the external validity of previously published results. TRIAL REGISTRATION: ClinicalTrials.gov; NCT02007083 10/12/2013, NCT02051374 31/01/2014 and NCT03562936 20/06/2018.

Is the presence of foraminal stenosis associated with outcome in lumbar spinal stenosis patients treated with posterior microsurgical decompression.

BACKGROUND: We aim to investigate associations between preoperative radiological findings of lumbar foraminal stenosis with clinical outcomes after posterior microsurgical decompression in patients with predominantly central lumbar spinal stenosis (LSS). METHODS: The study was an additional analysis in the NORDSTEN Spinal Stenosis Trial. In total, 230 men and 207 women (mean age 66.8 (SD 8.3)) were included. All patients underwent an MRI including T1- and T2-weighted sequences. Grade of foraminal stenosis was dichotomized into none to moderate (0-1) and severe (2-3) category using Lee's classification system. The Oswestry Disability Index (ODI), Zurich Claudication Questionnaire (ZCQ), and numeric rating scale (NRS) for back and leg pain were collected at baseline and at 2-year follow-up. Primary outcome was a reduction of 30% or more on the ODI score. Secondary outcomes included the mean improvement on the ODI, ZCQ, and NRS scores. We performed multivariable regression analyses with the radiological variates foraminal stenosis, Pfirrmann grade, Schizas score, dural sac cross-sectional area, and the possible plausible confounders: patients' gender, age, smoking status, and BMI. RESULTS: The cohort of 437 patients presented a high degree of degenerative changes at baseline. Of 414 patients with adequate imaging of potential foraminal stenosis, 402 were labeled in the none to moderate category and 12 in the severe category. Of the patients with none to moderate foraminal stenosis, 71% achieved at least 30% improvement in ODI. Among the patients with severe foraminal stenosis, 36% achieved at least 30% improvement in ODI. A significant association between severe foraminal stenosis and less chance of reaching the target of 30% improvement in the ODI score after surgery was detected: OR 0.22 (95% CI 0.06, 0.83), p=0.03. When investigating outcome as continuous variables, a similar association between severe foraminal stenosis and less improved ODI with a mean difference of 9.28 points (95%CI 0.47, 18.09; p=0.04) was found. Significant association between severe foraminal stenosis and less improved NRS pain in the lumbar region was also detected with a mean difference of 1.89 (95% CI 0.30, 3.49; p=0.02). No significant association was suggested between severe foraminal stenosis and ZCQ or NRS leg pain. CONCLUSION: In patients operated with posterior microsurgical decompression for LSS, a preoperative severe lumbar foraminal stenosis was associated with higher proportion of patients with less than 30% improvement in ODI. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov (22.11.2013) under the identifier NCT02007083.

Surgery in degenerative spondylolisthesis: does fusion improve outcome in subgroups? A secondary analysis from a randomized trial (NORDSTEN trial).

BACKGROUND CONTEXT: Patients with spinal stenosis and degenerative spondylolisthesis are treated surgically with decompression alone or decompression with fusion. However, there is debate regarding which subgroups of patients may benefit from additional fusion. PURPOSE: To investigate possible treatment effect modifiers and prognostic variables among patients operated for spinal stenosis and degenerative spondylolisthesis. DESIGN: A secondary exploratory study using data from the Norwegian Degenerative Spondylolisthesis and Spinal Stenosis (NORDSTEN-DS) trial. Patients were randomized to decompression alone or decompression with instrumented fusion. PATIENT SAMPLE: The sample in this study consists of 267 patients from a randomized multicenter trial involving 16 hospitals in Norway. Patients were enrolled from February 12, 2014, to December 18, 2017. The study did not include patients with degenerative scoliosis, severe foraminal stenosis, multilevel spondylolisthesis, or previous surgery. OUTCOME MEASURES: The primary outcome was an improvement of ≥ 30% on the Oswestry Disability Index score (ODI) from baseline to 2-year follow-up. METHODS: When investigating possible variables that could modify the treatment effect, we analyzed the treatment arms separately. When testing for prognostic factors we analyzed the whole cohort (both treatment groups). We used univariate and multiple regression analyses. The selection of variables was done a priori, according to the published trial protocol. RESULTS: Of the 267 patients included in the trial (183 female [67%]; mean [SD] age, 66 [7.6] years), complete baseline data for the variables required for the present analysis were available for 205 of the 267 individuals. We did not find any clinical or radiological variables at baseline that modified the treatment effect. Thus, none of the commonly used criteria for selecting patients for fusion surgery influenced the chosen primary outcome in the two treatment arms. For the whole cohort, less comorbidity (American Society of Anesthesiologists Classification [ASA], OR = 4.35; 95% confidence interval (CI [1.16-16.67]) and more preoperative leg pain (OR = 1.23; CI [1.02-1.50]) were significantly associated with an improved primary outcome. CONCLUSIONS: In this study on patients with degenerative spondylolisthesis, neither previously defined instability criteria nor other pre-specified baseline variables were associated with better clinical outcome if fusion surgery was performed. None of the analyzed variables can be applied to guide the decision for fusion surgery in patients with degenerative spondylolisthesis. For both treatment groups, less comorbidity and more leg pain were associated with improved outcome 2 years after surgery. TRIAL REGISTRATION: NORDSTEN-DS ClinicalTrials.gov, NCT02051374.

Postoperative Dural Sac Cross-Sectional Area as an Association for Outcome After Surgery for Lumbar Spinal Stenosis: Clinical and Radiological Results From the NORDSTEN-Spinal Stenosis Trial.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: The aim was to investigate the association between postoperative dural sac cross-sectional area (DSCA) after decompressive surgery for lumbar spinal stenosis and clinical outcome. Furthermore, to investigate if there is a minimum threshold for how extensive a posterior decompression needs to be to achieve a satisfactory clinical result. SUMMARY OF BACKGROUND DATA: There is limited scientific evidence for how extensive lumbar decompression needs to be to obtain a good clinical outcome in patients with symptomatic lumbar spinal stenosis. MATERIALS AND METHODS: All patients were included in the Spinal Stenosis Trial of the NORwegian Degenerative spondylolisthesis and spinal STENosis (NORDSTEN)-study. The patients underwent decompression according to three different methods. DSCA measured on lumbar magnetic resonance imaging at baseline and at three months follow-up, and patient-reported outcome at baseline and at two-year follow-up were registered in a total of 393 patients. Mean age was 68 (SD: 8.3), proportion of males were 204/393 (52%), proportion of smokers were 80/393 (20%), and mean body mass index was 27.8 (SD: 4.2).The cohort was divided into quintiles based on the achieved DSCA postoperatively, the numeric, and relative increase of DSCA, and the association between the increase in DSCA and clinical outcome were evaluated. RESULTS: At baseline, the mean DSCA in the whole cohort was 51.1 mm 2 (SD: 21.1). Postoperatively the area increased to a mean area of 120.6 mm 2 (SD: 46.9). The change in Oswestry disability index in the quintile with the largest DSCA was -22.0 (95% CI: -25.6 to -18), and in the quintile with the lowest DSCA the Oswestry disability index change was -18.9 (95% CI: -22.4 to -15.3). There were only minor differences in clinical improvement for patients in the different DSCA quintiles. CONCLUSION: Less aggressive decompression performed similarly to wider decompression across multiple different patient-reported outcome measures at two years following surgery.

Menopausal hormone therapy, oral contraceptives and risk of chronic low back pain: the HUNT Study.

BACKGROUND: There are indications that use of menopausal hormone therapy (MHT) and oral contraceptives (OC) increases the risk of low back pain (LBP), with higher oestrogen levels involved in the underlying mechanisms. The purpose of the present study was to investigate associations between use of systemic MHT or OC and risk of chronic LBP in a large population-based data set. METHODS: Data were obtained from two surveys in the Trøndelag Health Study in Norway, HUNT2 (1995-1997) and HUNT3 (2006-2008). A cross-sectional study of association between use of systemic MHT and prevalence of chronic LBP comprised 12,974 women aged 40-69 years in HUNT2, with 4007 women reporting chronic LBP. A cohort study involving MHT comprised 6007 women without chronic LBP at baseline in HUNT2, and after 11 years 1245 women reported chronic LBP at follow-up in HUNT3. The cross-sectional study of association with use of OC included 23,593 women aged 20-69 years in HUNT2, with 6085 women reporting chronic LBP. The corresponding cohort study included 10,586 women without chronic LBP at baseline in HUNT2, of whom 2084 women reported chronic LBP in HUNT3. Risk of chronic LBP was examined in both study designs in generalised linear models with adjustment for potential confounders. RESULTS: In the cohort study, current users of systemic MHT at baseline showed a greater risk of chronic LBP (relative risk (RR) 1.30; 95% CI: 1.14-1.49; compared with never users). The risk increased according to duration of MHT use (P for linear trend = 0.003). Known users of systemic MHT based exclusively on oestrogen experienced the highest risk (RR 1.49; 95% CI: 1.16-1.91), but an increased risk was also seen among known users of oestrogen-progestin combination MHT (RR 1.35; 95% CI: 1.16-1.57). A slight increase in risk of chronic LBP was found in the cohort study among former users of OC (RR 1.17; 95% CI: 1.06-1.30; compared with never users). CONCLUSIONS: Long-lasting use of systemic MHT, in particular therapy based on oestrogen only, is associated with greater risk of chronic LBP. Having been a user of OC most likely entails a minor increase in risk.

Amoxicillin Did Not Reduce Modic Change Edema in Patients With Chronic Low Back Pain: Subgroup Analyses of a Randomised Trial (the AIM Study).

STUDY DESIGN: Exploratory subgroup analyses of a randomised trial [Antibiotics in Modic changes (AIM) study]. OBJECTIVE: The aim was to assess the effect of amoxicillin versus placebo in reducing Modic change (MC) edema in patients with chronic low back pain. SUMMARY OF BACKGROUND DATA: The AIM study showed a small, clinically insignificant effect of amoxicillin on pain-related disability in patients with chronic low back pain and MC type 1 (edema type) on magnetic resonance imaging (MRI). MATERIALS AND METHODS: A total of 180 patients were randomised to receive 100 days of amoxicillin or placebo. MC edema was assessed on MRI at baseline and one-year follow-up. Per-protocol analyses were conducted in subgroups with MC edema on short tau inversion recovery (STIR) or T1/T2-weighted MRI at baseline. MC edema reductions (yes/no) in STIR and T1/T2 series were analyzed separately. The effect of amoxicillin in reducing MC edema was analyzed using logistic regression adjusted for prior disk surgery. To assess the effect of amoxicillin versus placebo within the group with the most abundant MC edema on STIR at baseline ("STIR3" group), we added age, STIR3 (yes/no), and STIR3×treatment group (interaction term) as independent variables and compared the marginal means (probabilities of edema reduction). RESULTS: Compared to placebo, amoxicillin did not reduce MC edema on STIR (volume/intensity) in the total sample with edema on STIR at baseline (odds ratio 1.0, 95% CI: 0.5, 2.0; n=141) or within the STIR3 group (probability of edema reduction 0.69, 95% CI: 0.47, 0.92 with amoxicillin and 0.61, 95% CI: 0.43, 0.80 with placebo; n=41). Compared with placebo, amoxicillin did not reduce MC edema in T1/T2 series (volume of the type 1 part of MCs) (odds ratio: 1.0, 95% CI: 0.5, 2.3, n=104). Edema declined in >50% of patients in both treatment groups. CONCLUSIONS: From baseline to one-year follow-up, amoxicillin did not reduce MC edema compared with placebo. LEVEL OF EVIDENCE: 2.

The association between preoperative MRI findings and clinical improvement in patients included in the NORDSTEN spinal stenosis trial.

PURPOSE: To investigate potential associations between preoperative MRI findings and patient reported outcome measures (PROMs) after surgery for lumbar spinal stenosis (LSS). METHODS: The NORDSTEN trial included 437 patients. We investigated the association between preoperative MRI findings such as morphological grade of stenosis (Schizas grade), quantitative grade of stenosis (dural sac cross-sectional area), disc degeneration (Pfirrmann score), facet joint tropism and fatty infiltration of the multifidus muscle, and improvement in patient reported outcome measures (PROMs) 2 years after surgery. We dichotomized each radiological parameter into a moderate or severe category. PROMs i.e., Oswestry Disability Index (ODI), Zurich Claudication Questionnaire (ZCQ) and Numeric rating scale (NRS) for back and leg pain were collected before surgery and at 2 year follow-up. In the primary analysis, we investigated the association between MRI findings and ODI score (dichotomized to ≥ 30% improvement or not). In the secondary analysis, we investigated the association between MRI findings and the mean improvement on the ODI-, ZCQ- and NRS scores. We used multivariable regression models adjusted for patients' gender, age, smoking status and BMI. RESULTS: The primary analysis showed that severe disc degeneration (Pfirrmann score 4-5) was significantly associated with less chance of achieving a 30% improvement on the ODI score (OR 0.54, 95% CI 0.34, 0.88). In the secondary analysis, we detected no clinical relevant associations. CONCLUSION: Severe disc degeneration preoperatively suggest lesser chance of achieving 30% improvement in ODI score after surgery for LSS. Other preoperative MRI findings were not associated with patient reported outcome.

Correlation between gene expression and MRI STIR signals in patients with chronic low back pain and Modic changes indicates immune involvement.

Disability and distress caused by chronic low back pain (LBP) lacking clear pathoanatomical explanations cause huge problems both for patients and society. A subgroup of patients has Modic changes (MC), identifiable by MRI as vertebral bone marrow lesions. The cause of such changes and their relationship to pain are not yet understood. We explored the pathobiology of these lesions using profiling of gene expression in blood, coupled with an edema-sensitive MRI technique known as short tau inversion recovery (STIR) imaging. STIR images and total RNA from blood were collected from 96 patients with chronic LBP and MC type I, the most inflammatory MC state. We found the expression of 37 genes significantly associated with STIR signal volume, ten genes with edema abundancy (a constructed combination of STIR signal volume, height, and intensity), and one gene with expression levels significantly associated with maximum STIR signal intensity. Gene sets related to interferon signaling, mitochondrial metabolism and defense response to virus were identified as significantly enriched among the upregulated genes in all three analyses. Our results point to inflammation and immunological defense as important players in MC biology in patients with chronic LBP.

Clinical and MRI findings in lumbar spinal stenosis: baseline data from the NORDSTEN study.

PURPOSE: The aim was to describe magnetic resonance imaging findings in patients planned for lumbar spinal stenosis surgery. Further, to describe possible associations between MRI findings and patient characteristics with patient reported disability or pain. METHODS: The NORDSTEN spinal stenosis trial included 437 patients planned for surgical decompression of LSS. The following MRI findings were evaluated before surgery: morphological (Schizas) and quantitative (cross-sectional area) grade of stenosis, disk degeneration (Pfirrmann), facet joint tropism and fatty infiltration of the multifidus muscle. Patients were dichotomized into a moderate or severe category for each radiological parameter classification. A multivariable linear regression analysis was performed to investigate the association between MRI findings and preoperative scores for Oswestry Disability Index, Zurich Claudication Questionnaire and Numeric rating scale for back and leg pain. The following patient characteristics were included in the analysis: gender, age, smoking and weight. RESULTS: The percentage of patients with severe scores was as follows: Schizas (C + D) 71.3%, cross-sectional area (< 75 mm2) 86.8%, Pfirrmann (4 + 5) 58.1%, tropism (≥ 15°) 11.9%, degeneration of multifidus muscle (2-4) 83.7%. Regression coefficients indicated minimal changes in severity of symptoms when comparing the groups with moderate and severe MRI findings. Only gender had a significant and clinically relevant association with ODI score. CONCLUSION: In this cross-sectional study, the majority of the patients had MRI findings classified as severe LSS changes, but the findings had no clinically relevant association with patient reported disability and pain at baseline. Patient characteristics have a larger impact on disability and pain than radiological findings. TRIAL REGISTRATION: www. CLINICALTRIALS: gov identifier: NCT02007083, registered December 2013.

Decompression with or without Fusion in Degenerative Lumbar Spondylolisthesis.

BACKGROUND: In patients with lumbar spinal stenosis and degenerative spondylolisthesis, it is uncertain whether decompression surgery alone is noninferior to decompression with instrumented fusion. METHODS: We conducted an open-label, multicenter, noninferiority trial involving patients with symptomatic lumbar stenosis that had not responded to conservative management and who had single-level spondylolisthesis of 3 mm or more. Patients were randomly assigned in a 1:1 ratio to undergo decompression surgery (decompression-alone group) or decompression surgery with instrumented fusion (fusion group). The primary outcome was a reduction of at least 30% in the score on the Oswestry Disability Index (ODI; range, 0 to 100, with higher scores indicating more impairment) during the 2 years after surgery, with a noninferiority margin of -15 percentage points. Secondary outcomes included the mean change in the ODI score as well as scores on the Zurich Claudication Questionnaire, leg and back pain, the duration of surgery and length of hospital stay, and reoperation within 2 years. RESULTS: The mean age of patients was approximately 66 years. Approximately 75% of the patients had leg pain for more than a year, and more than 80% had back pain for more than a year. The mean change from baseline to 2 years in the ODI score was -20.6 in the decompression-alone group and -21.3 in the fusion group (mean difference, 0.7; 95% confidence interval [CI], -2.8 to 4.3). In the modified intention-to-treat analysis, 95 of 133 patients (71.4%) in the decompression-alone group and 94 of 129 patients (72.9%) in the fusion group had a reduction of at least 30% in the ODI score (difference, -1.4 percentage points; 95% CI, -12.2 to 9.4), showing the noninferiority of decompression alone. In the per-protocol analysis, 80 of 106 patients (75.5%) and 83 of 110 patients (75.5%), respectively, had a reduction of at least 30% in the ODI score (difference, 0.0 percentage points; 95% CI, -11.4 to 11.4), showing noninferiority. The results for the secondary outcomes were generally in the same direction as those for the primary outcome. Successful fusion was achieved with certainty in 86 of 100 patients (86.0%) who had imaging available at 2 years. Reoperation was performed in 15 of 120 patients (12.5%) in the decompression-alone group and in 11 of 121 patients (9.1%) in the fusion group. CONCLUSIONS: In this trial involving patients who underwent surgery for degenerative lumbar spondylolisthesis, most of whom had symptoms for more than a year, decompression alone was noninferior to decompression with instrumented fusion over a period of 2 years. Reoperation occurred somewhat more often in the decompression-alone group than in the fusion group. (NORDSTEN-DS ClinicalTrials.gov number, NCT02051374.).