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.

Dixon T2 imaging of vertebral bone edema: reliability and comparison with short tau inversion recovery.

BACKGROUND: It is uncertain whether T2-weighted Dixon water images (DixonT2w) and short tau inversion recovery (STIR) are interchangeable when evaluating vertebral bone edema, or if one method is superior or visualizes the edema differently. PURPOSE: To compare image quality and Modic change (MC)-related edema between DixonT2w and STIR and estimate inter-observer reliability for MC edema on DixonT2w. MATERIAL AND METHODS: Consecutive patients (n = 120) considered for the Antibiotics in Modic changes (AIM) trial underwent lumbar 1.5-T magnetic resonance imaging with two-point DixonT2w and STIR. Two radiologists assessed MC-related high-signal lesions on DixonT2w and compared image quality and lesion extent with STIR. Cohen's kappa and mean of differences ± limits of agreement were calculated. RESULTS: Fat suppression and artefacts were similar on DixonT2w and STIR in 116 of 120 (97%) patients. Lesion conspicuity was similar in 88, better on STIR in 10, and better on DixonT2w in 9 of 107 patients with MC-related high-signal lesions. Contrast-to-noise ratio for STIR versus DixonT2w was 19.1 versus 17.1 (mean of differences 2.0 ± 8.2). Of 228 lesions L4-S1, 215 (94%) had similar extent on DixonT2w and STIR, 11 were smaller/undetected on STIR, and two were smaller/undetected on DixonT2w. Lesions missed on STIR (n = 9) or DixonT2w (n = 1) had a weak signal increase on the other sequence (≤17%; 0% = vertebral body, 100% = cerebrospinal fluid). Inter-observer reliability (mean kappa L4-S1) was very good for presence (0.87), moderate for height (0.44), and good for volume (0.63) of lesions on DixonT2w. CONCLUSION: DixonT2w provided similar visualization of MC-related vertebral edema as STIR.

Apparent diffusion coefficient values in Modic changes - interobserver reproducibility and relation to Modic type.

BACKGROUND: Modic Changes (MCs) in the vertebral bone marrow were related to back pain in some studies but have uncertain clinical relevance. Diffusion weighted MRI with apparent diffusion coefficient (ADC)-measurements can add information on bone marrow lesions. However, few have studied ADC measurements in MCs. Further studies require reproducible and valid measurements. We expect valid ADC values to be higher in MC type 1 (oedema type) vs type 3 (sclerotic type) vs type 2 (fatty type). Accordingly, the purpose of this study was to evaluate ADC values in MCs for interobserver reproducibility and relation to MC type. METHODS: We used ADC maps (b 50, 400, 800 s/mm2) from 1.5 T lumbar spine MRI of 90 chronic low back pain patients with MCs in the AIM (Antibiotics In Modic changes)-study. Two radiologists independently measured ADC in fixed-sized regions of interests. Variables were MC-ADC (ADC in MC), MC-ADC% (0% = vertebral body, 100% = cerebrospinal fluid) and MC-ADC-ratio (MC-ADC divided by vertebral body ADC). We calculated mean difference between observers ± limits of agreement (LoA) at separate endplates. The relation between ADC variables and MC type was assessed using linear mixed-effects models and by calculating the area under the receiver operating characteristic curve (AUC). RESULTS: The 90 patients (mean age 44 years; 54 women) had 224 MCs Th12-S1 comprising type 1 (n = 111), type 2 (n = 91) and type 3 MC groups (n = 22). All ADC variables had higher predicted mean for type 1 vs 3 vs 2 (p < 0.001 to 0.02): MC-ADC (10- 6 mm2/s) 1201/796/576, MC-ADC% 36/21/14, and MC-ADC-ratio 5.9/4.2/3.1. MC-ADC and MC-ADC% had moderate to high ability to discriminate between the MC type groups (AUC 0.73-0.91). MC-ADC-ratio had low to moderate ability (AUC 0.67-0.85). At L4-S1, widest/narrowest LoA were for MC-ADC 20 ± 407/12 ± 254, MC-ADC% 1.6 ± 18.8/1.4 ± 10.4, and MC-ADC-ratio 0.3 ± 4.3/0.2 ± 3.9. Difference between observers > 50% of their mean value was less frequent for MC-ADC (9% of MCs) vs MC-ADC% and MC-ADC-ratio (17-20%). CONCLUSIONS: The MC-ADC variable (highest mean ADC in the MC) had best interobserver reproducibility, discriminated between MC type groups, and may be used in further research. ADC values differed between MC types as expected from previously reported MC histology.

Reliability of preoperative MRI findings in patients with lumbar spinal stenosis.

BACKGROUND: Magnetic Resonance Imaging (MRI) is an important tool in preoperative evaluation of patients with lumbar spinal stenosis (LSS). Reported reliability of various MRI findings in LSS varies from fair to excellent. There are inconsistencies in the evaluated parameters and the methodology of the studies. The purpose of this study was to evaluate the reliability of the preoperative MRI findings in patients with LSS between musculoskeletal radiologists and orthopaedic spine surgeons, using established evaluation methods and imaging data from a prospective trial. METHODS: Consecutive lumbar MRI examinations of candidates for surgical treatment of LSS from the Norwegian Spinal Stenosis and Degenerative Spondylolisthesis (NORDSTEN) study were independently evaluated by two musculoskeletal radiologists and two orthopaedic spine surgeons. The observers had a range of experience between six and 13 years and rated five categorical parameters (foraminal and central canal stenosis, facet joint osteoarthritis, redundant nerve roots and intraspinal synovial cysts) and one continuous parameter (dural sac cross-sectional area). All parameters were re-rated after 6 weeks by all the observers. Inter- and intraobserver agreement was assessed by Gwet's agreement coefficient (AC1) for categorical parameters and Intraclass Correlation Coefficient (ICC) for the dural sac cross-sectional area. RESULTS: MRI examinations of 102 patients (mean age 66 ± 8 years, 53 men) were evaluated. The overall interobserver agreement was substantial or almost perfect for all categorical parameters (AC1 range 0.67 to 0.98), except for facet joint osteoarthritis, where the agreement was moderate (AC1 0.39). For the dural sac cross-sectional area, the overall interobserver agreement was good or excellent (ICC range 0.86 to 0.96). The intraobserver agreement was substantial or almost perfect/ excellent for all parameters (AC1 range 0.63 to 1.0 and ICC range 0.93 to 1.0). CONCLUSIONS: There is high inter- and intraobserver agreement between radiologists and spine surgeons for preoperative MRI findings of LSS. However, the interobserver agreement is not optimal for evaluation of facet joint osteoarthritis. TRIAL REGISTRATION: www.ClinicalTrials.gov identifier: NCT02007083 , registered December 2013.

Oedema on STIR modified the effect of amoxicillin as treatment for chronic low back pain with Modic changes-subgroup analysis of a randomized trial.

OBJECTIVE: To evaluate potential MRI-defined effect modifiers of amoxicillin treatment in patients with chronic low back pain and type 1 or 2 Modic changes (MCs) at the level of a previous lumbar disc herniation (index level). METHODS: In a prospective trial (AIM), 180 patients (25-64 years; mean age 45; 105 women) were randomised to receive amoxicillin or placebo for 3 months. Primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (0-24 scale) at 1 year. Mean RMDQ score difference between the groups at 1 year defined the treatment effect; 4 RMDQ points defined the minimal clinically important effect. Predefined baseline MRI features of MCs at the index level(s) were investigated as potential effect modifiers. The predefined primary hypothesis was a better effect of amoxicillin when short tau inversion recovery (STIR) shows more MC-related high signal. To evaluate this hypothesis, we pre-constructed a composite variable with three categories (STIR1/2/3). STIR3 implied MC-related STIR signal increases with volume ≥ 25% and height > 50% of vertebral body and maximum intensity increase ≥ 25% and presence on both sides of the disc. As pre-planned, interaction with treatment was analysed using ANCOVA in the per protocol population (n = 155). RESULTS: The STIR3 composite group (n = 41) and STIR signal volume ≥ 25% alone (n = 45) modified the treatment effect of amoxicillin. As hypothesised, STIR3 patients reported the largest effect (- 5.1 RMDQ points; 95% CI - 8.2 to - 1.9; p for interaction = 0.008). CONCLUSIONS: Predefined subgroups with abundant MC-related index-level oedema on STIR modified the effect of amoxicillin. This finding needs replication and further support. KEY POINTS: • In the primary analysis of the AIM trial, the effect of amoxicillin in patients with chronic low back pain and type 1 or 2 MCs did not reach the predefined cut-off for clinical importance. • In the present MRI subgroup analysis of AIM, predefined subgroups with abundant MC-related oedema on STIR reported an effect of amoxicillin. • This finding requires replication and further support.

Clinical effect modifiers of antibiotic treatment in patients with chronic low back pain and Modic changes - secondary analyses of a randomised, placebo-controlled trial (the AIM study).

BACKGROUND: Randomised trials on antibiotic treatment for patients with chronic low back pain and vertebral endplate changes visible on MRI (Modic changes) have shown mixed results. A possible explanation might be a real treatment effect in subgroups of the study populations. The purpose of the present study was to explore potential clinical effect modifiers of 3-months oral amoxicillin treatment in patients with chronic low back pain and type I or II Modic changes at the level of a previous lumbar disc herniation. METHODS: We performed analyses of effect modifiers on data from AIM, a double-blind parallel-group multicentre trial. One hundred eighty patients with chronic low back pain, previous disc herniation, Modic change type I (n = 118) or type II (n = 62) were randomised to 3-months oral treatment with 750 mg amoxicillin (n = 89) or placebo (n = 91) three times daily. The primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (possible values 0-24) at 1-year follow-up in the intention-to-treat population. The predefined minimal clinically important between-group mean difference was 4 RMDQ points (not reached in the primary analysis of AIM). Predefined baseline characteristics were analysed as potential effect modifiers, four primary (type I Modic changes, previous disc surgery, positive pain provocation test, high CRP) and five exploratory (disturbed sleep, constant low back pain, short duration of low back pain, younger age, and male) using ANCOVA with interaction terms. RESULTS: None of the four primary potential effect modifiers had strong evidence of modifying the treatment effect. In patients younger than 40 years the difference in mean RMDQ score between the treatment groups was - 4.0 (95%CI, - 6.9 to - 1.2), compared to - 0.5 (95%CI, - 2.3 to 1.3) in patients 40 years or older, both in favour of amoxicillin treatment (exploratory analysis). CONCLUSIONS: We did not find evidence for convincing clinical effect modifiers of antibiotic treatment in patients with chronic low back pain and Modic changes. Our results for younger age in these explorative analyses should not affect clinical treatment decisions without confirmation in future studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT02323412 , First registered 23 December 2014.

Association of Modic change types and their short tau inversion recovery signals with clinical characteristics- a cross sectional study of chronic low back pain patients in the AIM-study.

BACKGROUND: Modic Changes (MCs, magnetic resonance imaging (MRI) signal changes in the vertebral bone marrow extending from the vertebral endplate) may represent a subgroup of nonspecific chronic low back pain that could benefit from a specific management. The primary aim was to compare clinical characteristics between patients with type 1 versus type 2 MCs. The secondary aim was to explore associations between clinical characteristics and MC related short tau inversion recovery (STIR) signals. METHODS: This cross-sectional study used baseline data prospectively collected between 2015 and 2017 on the 180 patients included in the AIM-study (Antibiotics In Modic changes), a randomized controlled trial in a Norwegian hospital out-patient setting of patients with chronic low back pain, a lumbar disc herniation within the last 2 years, low back pain intensity score ≥ 5 (on a 0-10 scale) and current type 1 or type 2 MCs at the previously herniated lumbar disc level. We used prespecified clinical characteristics including self-report measures, physiologic measures and functional measures from clinical history and examination. The diagnostic accuracy of various clinical characteristics to discriminate between patients with type 1 MCs (with or without additional type 2 MCs) and patents with type 2 MCs only (not type 1) were assessed by calculating the area under the receiver-operating curve. We assessed the correlations of clinical characteristics with details of MC related STIR signal increase. RESULTS: No clinical characteristic differed between patients with type 1 (n = 118) versus type 2 (but not type 1) (n = 62) MCs. The clinical characteristics showed no/minor differences or no/weak correlations with MC related STIR signal increase. Patients with a positive Springing test (at any lumbar level) had slightly less volume of STIR signal increase than those with a negative test (mean difference 1.3 on a 0-48 scale, 95% CI 0.3 to 2.3). CONCLUSION: Clinical characteristics were similar for patients with type 1 MCs and patients with type 2 MCs, and showed no clinically relevant correlations with MC related STIR signal increase. TRIAL REGISTRATION: ClinicalTrials.gov NCT02323412, First registered 23 December 2014.

The effect of infliximab in patients with chronic low back pain and Modic changes (the BackToBasic study): study protocol of a randomized, double blind, placebo-controlled, multicenter trial.

BACKGROUND: Low back pain is common and a significant number of patients experience chronic low back pain. Current treatment options offer small to moderate effects. Patients with vertebral bone marrow lesions visualized as Modic changes on magnetic resonance imaging may represent a subgroup within the low back pain population. There is evidence for inflammatory mediators being involved in development of Modic changes; hence, suppression of inflammation could be a treatment strategy for these patients. This study examines the effect of anti-inflammatory treatment with the TNF-α inhibitor infliximab in patients with chronic low back pain and Modic changes. METHODS/DESIGN: The BackToBasic trial is a multicenter, double blind, randomized controlled trial conducted at six hospitals in Norway, comparing intravenous infusions with infliximab with placebo. One hundred twenty-six patients aged 18-65 with chronic low back pain and type 1 Modic changes will be recruited from secondary care outpatients' clinics. The primary outcome is back pain-specific disability at day 154 (5 months). The study is designed to detect a difference in change of 10 (SD 18) in the Oswestry Disability Index at day 154/ 5 months. The study also aims to refine MRI-assessment, investigate safety and cost-effectiveness and explore the underlying biological mechanisms of Modic changes. DISCUSSION: Finding treatments that target underlying mechanisms could pose new treatment options for patients with low back pain. Suppression of inflammation could be a treatment strategy for patients with low back pain and Modic changes. This paper presents the design of the BackToBasic study, where we will assess the effect of an anti-inflammatory treatment versus placebo in patients with chronic low back pain and type 1 Modic changes. The study is registered at ClinicalTrials.gov under the identifier NCT03704363 . The EudraCT Number: 2017-004861-29.

Facet arthropathy evaluation: CT or MRI?

OBJECTIVE: To assess the reliability of lumbar facet arthropathy evaluation with computed tomography (CT) or magnetic resonance imaging (MRI) in patients with and without lumbar disc prosthesis and to estimate the reliability for individual CT and MRI findings indicating facet arthropathy. METHODS: Metal-artifact reducing CT and MRI protocols were performed at follow-up of 114 chronic back pain patients treated with (n = 66) or without (n = 48) lumbar disc prosthesis. Three experienced radiologists independently rated facet joint space narrowing, osteophyte/hypertrophy, erosions, subchondral cysts, and total grade facet arthropathy at each of the three lower lumbar levels on both CT and MRI, using Weishaupt et al's rating system. CT and MRI examinations were randomly mixed and rated independently. Findings were dichotomized before analysis. Overall kappa and (due to low prevalence) prevalence- and bias-adjusted kappa were calculated to assess interobserver agreement. RESULTS: Interobserver agreement on total grade facet arthropathy was moderate at all levels with CT (kappa 0.47-0.48) and poor to fair with MRI (kappa 0.20-0.32). Mean prevalence- and bias-adjusted kappa was lower for osteophyte/hypertrophy versus other individual findings (CT 0.58 versus 0.79-0.86, MRI 0.35 versus 0.81-0.90), higher with CT versus MRI when rating osteophyte/hypertrophy (0.58 versus 0.35) and total grade facet arthropathy (0.54 versus 0.31), and generally similar at levels with versus levels without disc prosthesis. CONCLUSION: Interobserver agreement on facet arthropathy was moderate with CT and better with CT than with MRI. Disc prosthesis did not influence agreement. A more reliable grading of facet arthropathy requires a more consistent evaluation of osteophytes/hypertrophy. KEY POINTS: • In this study, interobserver agreement on facet arthropathy (FA) severity-based on facet joint space narrowing, osteophyte/hypertrophy, erosions, and subchondral cysts-was better with CT versus MRI. • Metal-artifact reducing CT and MRI protocols helped to improve visibility and maintain agreement when evaluating severity of FA at levels with metallic disc prosthesis. • Agreement was poorer for severity of osteophytes/hypertrophy than for the other evaluated FA findings; improved agreement on total grade FA evaluated with CT or MRI thus requires more consistent grading of osteophytes/hypertrophy between different radiologists.

Five-year development of lumbar disc degeneration-a prospective study.

OBJECTIVE: To examine the impact of demographic, clinical, and genetic factors as well as herniated discs on 5-year development of disc degeneration in the lumbar spine, and to investigate associations between changes in lumbar degenerative findings and pain. MATERIALS AND METHODS: In 144 patients with lumbar radicular pain or low back pain, we scored disc degeneration, herniated discs, and high-intensity zones in the posterior annulus fibrosus on lumbar magnetic resonance imaging (MRI) at baseline and 5-year follow-up. Genotyping (TaqMan assay) was performed for genes encoding vitamin D receptor (VDR), collagen XIα (COL11A), matrix metalloproteinase 1/9 (MMP1/MMP9), and interleukin 1α/1RN (IL-1α/IL-1RN). Associations were analyzed using multivariate linear regression adjusted for age, sex, smoking, body mass index, and baseline scores for degenerated discs and herniated discs (when analyzing impact of baseline factors) or for pain (when analyzing associations with pain). RESULTS: Progression of disc degeneration over 5 years was significantly (p < 0.001) related to higher age and less disc degeneration at baseline, but not to sex, smoking, body mass index, herniated discs, or variants in the studied genes. No associations were identified between changes in disc degeneration or high-intensity zones and pain at 5-year follow-up. However, increased number of herniated discs over 5 years was associated with pain at rest (p = 0.019). CONCLUSIONS: Age and disc degeneration at baseline, rather than genetic factors, influenced the 5-year development of disc degeneration in patients with lumbar radicular pain or low back pain. Development of herniated discs was related to pain at rest.

Lumbar total disc replacement: predictors for long-term outcome.

PURPOSE: We aimed to identify patient characteristics associated with favourable long-term outcomes after lumbar total disc replacement (TDR). METHODS: We analysed a cohort of 82 patients with degenerative disc and chronic low back pain (LBP) who were treated with TDR and originally participated in a randomised trial comparing TDR and multidisciplinary rehabilitation. Potential predictors were measured at baseline, and the outcomes assessed 8 years after they received allocated treatment. Outcome measures were dichotomised according to whether the participants achieved a clinically important functional improvement (15 points or more on the Oswestry Disability Index, ODI) (primary outcome) and whether they were employed at 8-year follow-up (secondary outcome). Associations between potential predictors and outcomes were modelled using logistic regression. For the secondary outcome, the results were also organised in a prediction matrix and expressed as probabilities. RESULTS: For 71 patients treated with TDR according to protocol, the follow-up time was 8 years. For a subgroup of 11 patients randomised to rehabilitation who crossed over and received TDR, the median postoperative follow-up time was 72 (range 41-88) months. Of all assessed baseline variables, only presence of Modic changes (type 1 and/or 2) was statistically significantly associated with an improvement of ≥ 15 ODI points. The probability of employment at 8-year follow-up was 1% for patients with ≥ 1 year of sick leave, comorbidity, ODI ≥ 50 and ≤ 9 years of education prior to treatment, and 87% for patients with < 1 year of sick leave, no comorbidity, ODI < 50 and higher education. CONCLUSIONS: Patients with Modic changes prior to the TDR surgery were more likely to report a clinically important functional improvement at long-term follow-up. Comorbidity, low level of education, long-term sick leave and high ODI score at baseline were associated with unemployment at long-term follow-up.

Fat in the lumbar multifidus muscles - predictive value and change following disc prosthesis surgery and multidisciplinary rehabilitation in patients with chronic low back pain and degenerative disc: 2-year follow-up of a randomized trial.

BACKGROUND: Evidence is lacking on whether fat infiltration in the multifidus muscles affects outcomes after total disc replacement (TDR) surgery and if it develops after surgery. The aims of this study were 1) to investigate whether pre-treatment multifidus muscle fat infiltration predicts outcome 2 years after treatment with TDR surgery or multidisciplinary rehabilitation, and 2) to compare changes in multifidus muscle fat infiltration from pre-treatment to 2-year follow-up between the two treatment groups. METHODS: The study is secondary analysis of data from a trial with 2-year follow-up of patients with chronic low back pain (LBP) and degenerative disc randomized to TDR surgery or multidisciplinary rehabilitation. We analyzed (aim 1) patients with both magnetic resonance imaging (MRI) at pre-treatment and valid data on outcome measures at 2-year follow-up (predictor analysis), and (aim 2) patients with MRI at both pre-treatment and 2-year follow-up. Outcome measures were visual analogue scale (VAS) for LBP, Oswestry Disability Index (ODI), work status and muscle fat infiltration on MRI. Patients with pre-treatment MRI and 2-year outcome data on VAS for LBP (n = 144), ODI (n = 147), and work status (n = 137) were analyzed for prediction purposes. At 2-year follow-up, 126 patients had another MRI scan, and change in muscle fat infiltration was compared between the two treatment groups. Three radiologists visually quantified multifidus muscle fat in the three lower lumbar levels on MRI as <20% (grade 0), 20-50% (grade 1), or >50% (grade 2) of the muscle cross-section containing fat. Regression analysis and a mid-P exact test were carried out. RESULTS: Grade 0 pre-treatment multifidus muscle fat predicted better clinical results at 2-year follow-up after TDR surgery (all outcomes) but not after rehabilitation. At 2-year follow-up, increased fat infiltration was more common in the surgery group (intention-to-treat p = 0.03, per protocol p = 0.08) where it was related to worse pain and ODI. CONCLUSIONS: Patients with less fat infiltration of multifidus muscles before TDR surgery had better outcomes at 2-year follow-up, but findings also indicated a negative influence of TDR surgery on back muscle morphology in some patients. The rehabilitation group maintained their muscular morphology and were unaffected by pre-treatment multifidus muscle fat. TRIAL REGISTRATION: NCT 00394732 (retrospectively registered October 31, 2006).

The role of imaging specialists as authors of systematic reviews on diagnostic and interventional imaging and its impact on scientific quality: report from the EuroAIM Evidence-based Radiology Working Group.

PURPOSE: To evaluate the inclusion of radiologists or nuclear medicine physicians (imaging specialists) as authors of systematic reviews (SRs) on imaging and imaging-guided diagnostic procedures and to determine the impact of imaging specialists' presence as authors on the overall quality of the reviews. MATERIALS AND METHODS: A MEDLINE and EMBASE search was performed for SRs of diagnostic and interventional image-guided procedures that were published from January 2001 to December 2010. SRs about procedures primarily performed by nonimaging specialists were excluded. The inclusion of imaging specialists among the SR authors and the frequency of publication in imaging journals were evaluated. The quality of a subset of 200 SRs (100 most recent SRs with imaging specialists as authors and 100 most recent SRs without imaging specialists as authors) was rated by using a 12-item modified assessment of multiple SRs (AMSTAR) evaluation tool. Spearman, χ(2), and Mann-Whitney statistics were used. RESULTS: From among 3258 retrieved citations, 867 SRs were included in the study. Neuroimaging had the largest number of SRs (28% [241 of 867]), 41% (354 of 867) of SRs concerned diagnostic performance, and 26% (228 of 867) of SRs were published in imaging journals. Imaging specialists were authors (in any position) in 330 (38%) of 867 SRs; they were first authors of 176 SRs and last authors of 161 SRs. SRs with imaging specialists as authors were more often published in imaging journals than in nonimaging journals (54% [179 of 330] vs 9% [49 of 537]; P < .001). The median number of modified AMSTAR quality indicators was nine in SRs with imaging specialists as authors, while that in SRs without imaging specialists as authors was seven (P = .003). CONCLUSION: Only 38% (330 of 867) of SRs on radiology or nuclear medicine-related imaging published from January 2001 to December 2010 included imaging specialists as authors. However, the inclusion of imaging specialists as authors was associated with a significant increase in the scientific quality (as judged by using a modified AMSTAR scale) of the SR.

The association between Modic changes and pain during 1-year follow-up in patients with lumbar radicular pain.

OBJECTIVE: To examine whether Modic changes influence pain during a 1-year follow-up in patients with lumbar radicular pain. MATERIALS AND METHODS: A total of 243 patients with lumbar radicular pain due to disc herniation were recruited from two hospitals in Norway and followed up at 6 weeks, 6 months, and 12 months. On baseline lumbar magnetic resonance images, two observers independently evaluated Modic changes (types I-III; craniocaudal size 0-3). Outcomes were sensory pain (McGill Pain Questionnaire), back and leg pain (visual analogue scale, VAS). Association between Modic type and outcomes was explored with a mixed model and then by two-way analysis of variance (ANOVA) at each time point with Modic and treatment groups (surgical, n = 126; nonsurgical, n = 117) as fixed factors, adjusted for disc degeneration, age, sex, smoking, and duration of radicular pain. Modic size was also analyzed using ANOVA. RESULTS: Pain scores had decreased significantly at 1-year follow-up. Modic type was significantly related to McGill sensory scores (mixed model: p = 0.014-0.026; ANOVA: p = 0.007 at 6 weeks), but not to VAS back pain or VAS leg pain scores. At 6 weeks, the mean McGill sensory score was higher in Modic I than in Modic II-III patients (p = 0.003) and in patients without Modic changes (p = 0.018). Modic size L1-S1 was not associated with pain outcomes. CONCLUSION: Patients with lumbar radicular pain have a substantial pain reduction during 1-year follow-up, but Modic type I changes may imply a slower initial decrease in sensory pain.

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.

Are two readers more reliable than one? A study of upper neck ligament scoring on magnetic resonance images.

BACKGROUND: Magnetic resonance imaging (MRI) studies typically employ either a single expert or multiple readers in collaboration to evaluate (read) the image results. However, no study has examined whether evaluations from multiple readers provide more reliable results than a single reader. We examined whether consistency in image interpretation by a single expert might be equal to the consistency of combined readings, defined as independent interpretations by two readers, where cases of disagreement were reconciled by consensus. METHODS: One expert neuroradiologist and one trained radiology resident independently evaluated 102 MRIs of the upper neck. The signal intensities of the alar and transverse ligaments were scored 0, 1, 2, or 3. Disagreements were resolved by consensus. They repeated the grading process after 3-8 months (second evaluation). We used kappa statistics and intraclass correlation coefficients (ICCs) to assess agreement between the initial and second evaluations for each radiologist and for combined determinations. Disagreements on score prevalence were evaluated with McNemar's test. RESULTS: Higher consistency between the initial and second evaluations was obtained with the combined readings than with individual readings for signal intensity scores of ligaments on both the right and left sides of the spine. The weighted kappa ranges were 0.65-0.71 vs. 0.48-0.62 for combined vs. individual scoring, respectively. The combined scores also showed better agreement between evaluations than individual scores for the presence of grade 2-3 signal intensities on any side in a given subject (unweighted kappa 0.69-0.74 vs. 0.52-0.63, respectively). Disagreement between the initial and second evaluations on the prevalence of grades 2-3 was less marked for combined scores than for individual scores (P ≥ 0.039 vs. P ≤ 0.004, respectively). ICCs indicated a more reliable sum score per patient for combined scores (0.74) and both readers' average scores (0.78) than for individual scores (0.55-0.69). CONCLUSIONS: This study was the first to provide empirical support for the principle that an additional reader can improve the reproducibility of MRI interpretations compared to one expert alone. Furthermore, even a moderately experienced second reader improved the reliability compared to a single expert reader. The implications of this for clinical work require further study.

Do more MRI findings imply worse disability or more intense low back pain? A cross-sectional study of candidates for lumbar disc prosthesis.

OBJECTIVE: To examine whether combined magnetic resonance imaging (MRI) findings are related to the degree of disability and low back pain (LBP) in candidates for lumbar disc prosthesis surgery. MATERIALS AND METHODS: This cross-sectional study included 170 disc prosthesis candidates (mean age 41 years; 88 women) with chronic non-radicular LBP and localized disc degeneration. Experienced radiologists rated Modic changes and disc findings at L4-S1 on pre-treatment MRIs. An MRI total score (0-10) for findings at L4/L5 plus L5/S1 was calculated for Modic type I and/or II changes, a posterior high intensity zone (HIZ) in the disc, dark/black nucleus pulposus signal, and ≥40 % disc height decrease. We analyzed the relationship of the MRI total score to the Oswestry Disability Index (ODI) (n = 170) and LBP intensity scores (0-100 visual analogue scale, n = 165) using multiple linear regression and adjusting for age, gender, body mass index, smoking, and anxiety/depression. RESULTS: The MRI total score was not related to ODI (regression coefficient 0.12, p = 0.79) or LBP intensity (regression coefficient 0.64, p = 0.37). When individual MRI findings were analyzed, patients with HIZ at L5/S1 had slightly lower ODI scores (4.7 points, p = 0.02). In post hoc analyses, results remained unchanged after adding facet arthropathy to the MRI total score and adjusting also for physical workload and physical leisure-time activity. CONCLUSIONS: The combined MRI findings were not related to the degree of disability or the intensity of LBP. These degenerative MRI findings cannot explain variation in pre-treatment disability and pain in patients with chronic LBP accepted for disc prosthesis surgery.

Long-Term Use of Amoxicillin Is Associated with Changes in Gene Expression and DNA Methylation in Patients with Low Back Pain and Modic Changes.

Long-term antibiotics are prescribed for a variety of medical conditions, recently including low back pain with Modic changes. The molecular impact of such treatment is unknown. We conducted longitudinal transcriptome and epigenome analyses in patients (n = 100) receiving amoxicillin treatment or placebo for 100 days in the Antibiotics in Modic Changes (AIM) study. Gene expression and DNA methylation were investigated at a genome-wide level at screening, after 100 days of treatment, and at one-year follow-up. We identified intra-individual longitudinal changes in gene expression and DNA methylation in patients receiving amoxicillin, while few changes were observed in patients receiving placebo. After 100 days of amoxicillin treatment, 28 genes were significantly differentially expressed, including the downregulation of 19 immunoglobulin genes. At one-year follow-up, the expression levels were still not completely restored. The significant changes in DNA methylation (n = 4548 CpGs) were mainly increased methylation levels between 100 days and one-year follow-up. Hence, the effects on gene expression occurred predominantly during treatment, while the effects on DNA methylation occurred after treatment. In conclusion, unrecognized side effects of long-term amoxicillin treatment were revealed, as alterations were observed in both gene expression and DNA methylation that lasted long after the end of treatment.

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.

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.