Measurement of vertebral endplate bone marrow lesion (Modic change) composition with water-fat MRI and relationship to patient-reported outcome measures.

PURPOSE: Vertebral endplate bone marrow lesions ("Modic changes", MC) are associated with chronic low back pain (CLBP). Bone marrow composition in MC is poorly understood. The goals of this study were to: (1) measure bone marrow fat fraction (BMF) in CLBP patients with MC using water-fat MRI and (2) assess the relationship between BMF measurements and patient-reported clinical characteristics. METHODS: In this cross-sectional study, 42 CLBP patients (men, n = 21; age, 48 ± 12.4 years) and 18 asymptomatic controls (men, n = 10; 42.7 ± 12.8 years) underwent 3 T MRI between January 2016 and July 2018. Imaging consisted of T1- and T2-weighted sequences to evaluate MC and spoiled gradient-recalled echo sequence with asymmetric echoes and least-squares fitting to measure BMF. BMF was compared between vertebrae with and without MC using mixed effects models. The relationship between the BMF measurements and patient-reported disability scores was examined using regression. RESULTS: Twenty-seven subjects (26 CLBP, 1 control) had MC, and MC presence coincided with significantly altered BMF. In MC 1, BMF was lower than endplates without MC (absolute difference -22.3%; p < 0.001); in MC 2, BMF was higher (absolute difference 21.0%; p < 0.001). Absolute BMF differences between affected and unaffected marrow were larger in patients with greater disability (p = 0.029-0.032) and were not associated with pain (p = 0.49-0.83). CONCLUSION: BMF is significantly altered in MC. Water-fat MRI enables BMF measurements that may eventually form the basis for quantitative assessments of MC severity and progression.

Serum Biomarkers for Connective Tissue and Basement Membrane Remodeling are Associated with Vertebral Endplate Bone Marrow Lesions as Seen on MRI (Modic Changes).

Vertebral endplate bone marrow lesions, visualized on magnetic resonance imaging (MRI) as Modic changes (MC), are associated with chronic low back pain (cLBP). Since guidelines recommend against routine spinal MRI for cLBP in primary care, MC may be underdiagnosed. Serum biomarkers for MC would allow early diagnosis, inform clinical care decisions, and supplement treatment monitoring. We aimed to discover biomarkers in the blood serum that correlate with MC pathophysiological processes. For this single-site cross-sectional study, we recruited 54 subjects with 38 cLBP patients and 16 volunteers without a history of LBP. All subjects completed an Oswestry Disability Index (ODI) questionnaire and 10-cm Visual Analog Score (VAS) for LBP (VASback) and leg pain. Lumbar T1-weighted and fat-saturated T2-weighted MRI were acquired at 3T and used for MC classification in each endplate. Blood serum was collected on the day of MRI. Biomarkers related to disc resorption and bone marrow fibrosis were analyzed with enzyme-linked immune-absorbent assays. The concentration of biomarkers between no MC and any type of MC (AnyMC), MC1, and MC2 were compared. The Area Under the Curve (AUC) of the Receiver Operating Characteristics were calculated for each biomarker and for bivariable biomarker models. We found that biomarkers related to type III and type IV collagen degradation and formation tended to correlate with the presence of MC (p = 0.060-0.088). The bivariable model with the highest AUC was PRO-C3 + C4M and had a moderate diagnostic value for AnyMC in cLBP patients (AUC = 0.73, specificity = 78.9%, sensitivity = 73.7%). In conclusion, serum biomarkers related to the formation and degradation of type III and type IV collagen, which are key molecules in bone marrow fibrosis, correlated with MC presence. Bone marrow fibrosis may be an important pathophysiological process in MC that should be targeted in larger biomarker and treatment studies.

Paraspinal muscle denervation and balance impairment in lumbar spinal stenosis.

INTRODUCTION: Denervation of the paraspinal muscles may impair posture and displace the center of gravity. Therefore, we assessed balance impairment in patients with lumbar spinal stenosis (LSS) with and without paraspinal denervation. METHODS: Thirty-two women with LSS (15 symptomatic, 17 asymptomatic), aged 42-78 years, were assessed for disability, pain, and mobility, and underwent masked mini-paraspinal mapping (mPSM). Berg Balance Scale (BBS) and device-assisted balance (DAB) tests were used for balance assessment. RESULTS: The symptomatic group had worse balance and higher mPSM scores than the asymptomatic group. Among DAB tests, limit of stability (LOS) had the highest correlations with BBS and mPSM in the symptomatic group. CONCLUSIONS: Paraspinal denervation correlated highly with static and dynamic balance in symptomatic patients. We recommend paraspinal mapping, balance assessment, rehabilitation, and follow-up with the LOS test for symptomatic patients.

Influence of patient-specific factors when comparing multifidus fat infiltration between chronic low back pain patients and asymptomatic controls.

Introduction: Many studies have attempted to link multifidus (MF) fat infiltration with muscle quality and chronic low back pain (cLBP), but there is no consensus on these relationships. Methods: In this cross-sectional cohort study, 39 cLBP patients and 18 asymptomatic controls were included. The MF muscle was manually segmented at each lumbar disc level and fat fraction (FF) measurements were taken from the corresponding advanced imaging water-fat images. We assessed the distribution patterns of MF fat from L1L2 to L5S1 and compared these patterns between groups. The sample was stratified by age, sex, body mass index (BMI), subject-reported pain intensity (VAS), and subject-reported low back pain disability (oswestry disability index, ODI). Results: Older patients had significantly different MF FF distribution patterns compared to older controls (p < 0.0001). Male patients had 34.8% higher mean lumbar spine MF FF compared to male controls (p = 0.0006), significantly different MF FF distribution patterns (p = 0.028), 53.7% higher mean MF FF measurements at L2L3 (p = 0.037), and 50.6% higher mean MF FF measurements at L3L4 (p = 0.041). Low BMI patients had 29.7% higher mean lumbar spine MF FF compared to low BMI controls (p = 0.0077). High BMI patients only had 4% higher mean lumbar spine MF FF compared to high BMI controls (p = 0.7933). However, high BMI patients had significantly different MF FF distribution patterns compared to high BMI controls (p = 0.0324). Low VAS patients did not significantly differ from the control cohort for any of our outcomes of interest; however, high VAS patients had 24.3% higher mean lumbar spine MF FF values (p = 0.0011), significantly different MF FF distribution patterns (p < 0.0001), 34.7% higher mean MF FF at L2L3 (p = 0.040), and 34.6% higher mean MF FF at L3L4 (p = 0.040) compared to the control cohort. Similar trends were observed for ODI. Conclusions: This study suggests that when the presence of paraspinal muscle fat infiltration is not characteristic of an individual's age, sex, and BMI, it may be associated with lower back pain.

Comprehensive non-surgical treatment decreased the need for spine surgery in patients with spondylolisthesis: Three-year results.

BACKGROUND: Non-surgical treatment is the primary approach to degenerative conditions of the lumbar spine and may involve multiple modalities. There is little literature to guide an evidence-based approach to care. OBJECTIVE: To determine the effectiveness of CNT (comprehensive non-surgical treatment) in patients with degenerative spondylolisthesis (DS) and spondylolytic spondylolisthesis (SS), and to identify predictor variables for success of CNT in avoiding surgery. METHODS: All patients who underwent CNT for spondylolisthesis (n: 203) were included. CNT consisted of patient education, pain control with transforaminal epidural steroid injections (TFEs) and/or medications, and exercise programs. RESULTS: Surgical and non-surgical patients were similar in age, smoking status, comorbidity scores, facet joint widening, and translation of spondylolisthesis. After CNT, only 21.6% of patients with DS and 31.3% of patients with SS chose to have surgery in 3-years follow-up. The non-surgical group reported significantly better pain relief (73.6% vs 55%) after TFEs for a longer period (152.8 vs 45.6 days) and lower opioid use than the surgical group (28.2% vs 55.3%). CONCLUSIONS: CNT is effective in spondylolisthesis and more successful in DS than SS. CNT may decrease the need for surgery, particularly in patients who report pain relief greater than 70% for average five months after TFEs.

The Relationship Between Endplate Pathology and Patient-reported Symptoms for Chronic Low Back Pain Depends on Lumbar Paraspinal Muscle Quality.

STUDY DESIGN: Cross-sectional cohort study of chronic low back pain (CLBP) patients and matched controls. OBJECTIVE: To explore the interplay between vertebral endplate damage and adjacent paraspinal muscle (PSM) quality, and to test their association in a cohort of patients with CLBP and matched controls. SUMMARY OF BACKGROUND DATA: Nonspecific CLBP is challenging to diagnose, in part, due to uncertainty regarding the source of pain. Delineating interactions among potential CLBP mechanisms may enhance diagnosis and treatment customization. METHODS: We collected advanced MRI imaging on 52 adult subjects, including 38 CLBP patients and 14 age- and sex-matched asymptomatic control subjects. Mean multifidus and erector spinae fat fraction (FF) was measured throughout the spine using an IDEAL MRI sequence. Presence of cartilage endplate (CEP) defects was determined at each disc level using UTE MRI. Logistic regression was used to test association of PSM FF, CEP defects, modic changes (MC), disc degeneration, and their interplay. RESULTS: We observed that CEP defects were the strongest predictor of nonspecific CLBP (OR: 14.1, P < 0.01) even after adjusting for MC and disc degeneration (OR: 26.1, P = 0.04). PSM quality did not independently distinguish patient and control groups, except for patients with high self-reported disability.At specifically L4L5, CEP damage was most prevalent and CEP damage was significantly associated with CLBP (OR: 3.7, 95% CI: 1.2-21.5, P = 0.03). CEP damage at L4L5 was predictive of CLBP when adjacent to PSMs with greater FF (MF, OR 14.7, P = 0.04; ES, OR: 17.3, P = 0.03), but not when PSM FF was lower and comparable to values in control, asymptomatic subjects. CONCLUSION: These results demonstrate the clinically important reciprocity between passive and dynamic spinal stabilizers, and support the notion that therapies targeting the PSMs may provide clinical benefit even in the presence of other spinal pathologies. LEVEL OF EVIDENCE: 4.

Is IL-1ß Further Evidence for the Role of Propionibacterium acnes in Degenerative Disc Disease? Lessons From the Study of the Inflammatory Skin Condition Acne Vulgaris.

The pathogenesis of degenerative disc disease is a complex and multifactorial process in which genetics, mechanical trauma, altered loading and nutrition present significant etiological factors. Infection of the intervertebral disc with the anaerobic bacterium Propionibacterium acnes is now also emerging as a potentially new etiological factor. This human commensal bacterium is well known for its long association with the inflammatory skin condition acne vulgaris. A key component of inflammatory responses to P. acnes in acne appears to be interleukin (IL)-1ß. Similarly, in degenerative disc disease (DDD) there is compelling evidence for the fundamental roles of IL-1ß in its pathology. We therefore propose that P. acnes involvement in DDD is biologically very plausible, and that IL-1ß is the key inflammatory mechanism driving the host response to P. acnes infection. Since there is a solid theoretical basis for this phenomenon, we further propose that the relationship between P. acnes infection and DDD is causal.

Superior Recess Access of the Lumbar Facet Joint.

STUDY DESIGN: Descriptive approach to accessing the lumbar facet joint by superior recess. OBJECTIVE: This study is aimed to describe an approach to accessing the lumbar facet joint through targeting the superior recess during lumbar facet joint injections. SUMMARY OF BACKGROUND DATA: Lumbar facet joint injections are routinely performed for both the diagnosis and treatment of chronic low back pain. Previous studies either did not specify which part of the joint to target, or recommended targeting the inferior aspect of the joint to access the inferior recess. One study did mention the superior recess as an alternative to injecting the inferior recess, but none has focused on description of the technique. This is the first time this technique has been described. MATERIALS AND METHODS: The records and fluoroscopic images were reviewed for all patients over a period of 9 months (January-September 2012) using the proposed technique. This resulted in a total of 48 patients; 15 men, 29 women, and a total of 117 facet joint intra-articular injections. Among these 48 patients, injections were repeated in total of 4 cases. The average time of injections among 4 repeat cases was 121 days. The success of the procedure was confirmed with an arthrogram demonstrating contrast flowing from the superior recess inferiorly through the joint space. RESULTS: Successful access of the lumbar facet joint through puncture of the superior recess was seen in 114 cases, with 3 unsuccessful attempts to enter facet joints due to osteophytes at involved levels. There were no complications observed during the procedure. CONCLUSIONS: We find this approach to be highly successful, safe, and well tolerated by the patient and recommend it as a technique for access of the lumbar facet joint in those patients in whom direct puncture of the inferior recess is difficult.

The effect of transforaminal epidural steroid injections in patients with spondylolisthesis.

BACKGROUND: Transforaminal epidural steroid injection (TFE) is a widely accepted non-surgical treatment for pain in patients with spondylolisthesis. However, the effectiveness of TFE has not been compared in patients with degenerative (DS) and isthmic spondylolisthesis (IS). OBJECTIVE: To compare the effectiveness of bilateral TFEs in DS and IS. METHODS: Patients who underwent bilateral TFEs for spondylolisthesis at University of California San Francisco Orthopaedic Institute from 2009 to 2014 were evaluated retrospectively. RESULTS: DS patients (120 female, 51 male) were significantly older and had higher comorbidity than those with IS (18 female, 14 male). They had better pain relief after TFE than patients with IS (72.11 ± 27.46% vs 54.39 ± 34.31%; p = 0.009). The number of TFEs, the mean duration of pain relief after TFE, follow-up periods, translation and facet joint widening were similar in DS and IS groups (p > 0.05). DS group had higher successful treatment rate (66.1% vs 46.9%, p = 0.009) and longer duration of pain relief (181.29 ± 241.37 vs 140.07 ± 183.62 days, p = 0.065) compared to IS group. CONCLUSIONS: Bilateral TFEs at the level of spondylolisthesis effectively decreased pain in patients. TFEs provided better pain relief for longer duration in patients with DS than for those with IS.

Propionibacterium acnes biofilm is present in intervertebral discs of patients undergoing microdiscectomy.

BACKGROUND: In previous studies, Propionibacterium acnes was cultured from intervertebral disc tissue of ~25% of patients undergoing microdiscectomy, suggesting a possible link between chronic bacterial infection and disc degeneration. However, given the prominence of P. acnes as a skin commensal, such analyses often struggled to exclude the alternate possibility that these organisms represent perioperative microbiologic contamination. This investigation seeks to validate P. acnes prevalence in resected disc cultures, while providing microscopic evidence of P. acnes biofilm in the intervertebral discs. METHODS: Specimens from 368 patients undergoing microdiscectomy for disc herniation were divided into several fragments, one being homogenized, subjected to quantitative anaerobic culture, and assessed for bacterial growth, and a second fragment frozen for additional analyses. Colonies were identified by MALDI-TOF mass spectrometry and P. acnes phylotyping was conducted by multiplex PCR. For a sub-set of specimens, bacteria localization within the disc was assessed by microscopy using confocal laser scanning and FISH. RESULTS: Bacteria were cultured from 162 discs (44%), including 119 cases (32.3%) with P. acnes. In 89 cases, P. acnes was cultured exclusively; in 30 cases, it was isolated in combination with other bacteria (primarily coagulase-negative Staphylococcus spp.) Among positive specimens, the median P. acnes bacterial burden was 350 CFU/g (12 - ~20,000 CFU/g). Thirty-eight P. acnes isolates were subjected to molecular sub-typing, identifying 4 of 6 defined phylogroups: IA1, IB, IC, and II. Eight culture-positive specimens were evaluated by fluorescence microscopy and revealed P. acnes in situ. Notably, these bacteria demonstrated a biofilm distribution within the disc matrix. P. acnes bacteria were more prevalent in males than females (39% vs. 23%, p = 0.0013). CONCLUSIONS: This study confirms that P. acnes is prevalent in herniated disc tissue. Moreover, it provides the first visual evidence of P. acnes biofilms within such specimens, consistent with infection rather than microbiologic contamination.

Propionibacterium acnes infected intervertebral discs cause vertebral bone marrow lesions consistent with Modic changes.

Modic type I change (MC1) are vertebral bone marrow lesions adjacent to degenerated discs that are specific for discogenic low back pain. The etiopathogenesis is unknown, but occult discitis, in particular with Propionibacteria acnes (P. acnes), has been suggested as a possible etiology. If true, antibiotic therapy should be considered for patients with MC1. However, this hypothesis is controversial. While some studies report up to 40% infection rate in herniated discs, others fail to detect infected discs and attribute reports of positive cultures to contamination during sampling procedure. Irrespective of the clinical controversy, whether it is biologically plausible for P. acnes to cause MC1 has never been investigated. Therefore, the objective of this study was to test if P. acnes can proliferate within discs and cause reactive changes in the adjacent bone marrow. P. acnes was aseptically isolated from a symptomatic human L4/5 disc with MC1 and injected into rat tail discs. We demonstrate proliferation of P. acnes and up-regulation of IL-1 and IL-6 within three days of inoculation. At day-7, disc degeneration was apparent along with fibrotic endplate erosion. TNF-α immunoreactivity was enhanced within the effected endplates along with cellular infiltrates. The bone marrow appeared normal. At day-14, endplates and trabecular bone close to the disc were almost completely resorbed and fibrotic tissue extended into the bone marrow. T-cells and TNF-α immunoreactivity were identified at the disc/marrow junction. On MRI, bone marrow showed MC1-like changes. In conclusion, P. acnes proliferate within the disc, induce degeneration, and cause MC1-like changes in the adjacent bone marrow. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1447-1455, 2016.

Impact of brief or extended exercise training on the benefit of a dyspnea self-management program in COPD.

PURPOSE: To evaluate the differences in the long-term outcomes of dyspnea, exercise performance, health-related quality of life, and health resource utilization following a dyspnea self-management program with 3 different "doses" of supervised exercise. PATIENTS AND METHODS: In a prospective, randomized, single-blind, 1-year trial, patients with stable chronic obstructive pulmonary disease (N = 103; age 66 +/- 8, females 57; FEV1 44.8% +/- 14% predicted) were randomly assigned to either: (1) Dyspnea self-management program (DM); (2) DM plus 4 supervised exercise sessions (DM-exposure); or (3) DM plus 24 supervised exercise sessions (DM-training). The dyspnea self-management program included individualized education and demonstration of dyspnea self-management strategies, an individualized home walking prescription, and biweekly nurse telephone calls. Outcomes were measured at baseline and every 2 months for 1 year. RESULTS: The DM-training group had significantly greater improvements in dyspnea during incremental treadmill test and in exercise performance on the incremental and endurance treadmill tests at 6 and 12 months compared with the other 2 groups. Dyspnea with activities of daily living and self-reported physical functioning significantly improved for all groups over time. The dose-response relationship between supervised exercise and improvement in dyspnea present at 2 months was not sustained over the year. CONCLUSION: Consistent with previous findings from evaluation studies of pulmonary rehabilitation programs, the greater number of supervised exercise training sessions improved laboratory dyspnea and performance more than the other two doses of exercise. In the long term, the improvement in dyspnea with activities of daily living and physical functioning was similar for all 3 groups.

Studies in the modified Scoliosis Research Society Outcomes Instrument in adults: validation, reliability, and discriminatory capacity.

STUDY DESIGN: Observational study of patients with scoliosis and matched controls. OBJECTIVES: To determine the validity and reliability of the modified Scoliosis Research Society Outcomes Instrument (SRS-22) for use in the assessment of deformity in adults. To demonstrate the discriminate validity of the SRS-22 in differentiating between affected and unaffected adults. SUMMARY OF BACKGROUND DATA: Spinal deformity has an important impact on the general health status of adults. The magnitude of this impact has been difficult to measure and reported variably in the literature. The development of disease-specific outcomes tools permits improved sensitivity and specificity in measuring the patient's self-assessment of health status. An instrument for measuring disease-specific health status in adults with scoliosis has not been validated. MATERIALS AND METHODS: Observational study comparing the health status of adults affected by scoliosis and unaffected controls, matched for age, gender, and socioeconomic status. Pearson correlation analysis was used to determine the relationship of each domain within the SRS-22 and SF-36 with radiographic parameters including sagittal balance, coronal balance, and major curve correction. Discriminate validity of the modified SRS instrument was determined by a comparison of means between affected and unaffected cohorts. The validation of the SRS-22 was determined by criterion validity, using correlation analysis with comparable domains of the SF-36. The reliability of the SRS-22 was demonstrated using test-retest parity and Cronbach's alpha test for internal consistency. RESULTS: One hundred eighty adults were included in the study, 146 with scoliosis and 34 without. Adults with scoliosis scored significantly lower than unaffected controls on every domain of the SRS-22 and the SF-36. The floor and ceiling effect of the SRS-22 were less than observed in the SF-36 instrument. Pearson correlation analysis demonstrated no significant correlation between any radiographic process measure and any specific domain within the SRS-22 or the SF-36 (r < 0.25). Comparison of similar domains in the SRS-22 and the SF-36 demonstrates high correlation between the instruments. Test-retest analysis similarly demonstrates a high degree of reproducibility in each domain (r = 0.83-0.94). Cronbach's alpha test of internal consistency within each domain demonstrates intercorrelation values greater than 0.75 within each domain of the SRS-22. CONCLUSIONS: Adult scoliosis has a significant and measurable impact on affected patients compared with controls. There is a poor correlation between radiographic parameters of outcome and patient self-assessment of health status. The SRS-22 is a reliable instrument in adults as demonstrated by a high degree of internal consistency and reproducibility. The SRS-22 is a valid instrument for use in adult deformity as demonstrated by the criterion validity assessment with the SF-36. The study supports the use of the SRS-22 in the adult spinal deformity population.

Exercise training improves outcomes of a dyspnea self-management program.

PURPOSE: The purpose of this study was twofold: (1) to determine whether exercise training adds to the benefit of a dyspnea self-management (DM) program; and (2) to determine if there is a "dose response" to supervised exercise training (0, 4, or 24 sessions) in dyspnea, exercise performance, and health-related quality of life. METHODS: Subjects with chronic obstructive pulmonary disease (n = 103, 46 men, 57 women; age 66 +/- 8 years; forced expiratory volume in 1 second 44.8 +/- 14% predicted) were randomized to DM, DM-exposure, or DM-training. Dyspnea self-management included individualized education about dyspnea management strategies, a home-walking prescription, and daily logs. Outcomes were measured at baseline and 2 months as part of a 1-year longitudinal randomized clinical trial. Outcomes included dyspnea during laboratory exercise and with activities of daily living (Chronic Respiratory Questionnaire [CRQ]), Shortness of Breath Questionnaire, Baseline/Transitional Dyspnea Index), exercise performance (incremental treadmill tests (ITTs) and endurance treadmill tests (ETTs), 6-minute walk (6MW), and health-related quality of life (SF-36). RESULTS: The DM-training group had significantly greater improvements than the DM-exposure and the DM groups in dyspnea at isotime during ITT (P =.006); exercise performance during ITT (P =.005), ETT (P =.003), and 6MW (P =.01); SF-36 Vitality (P =.031); and CRQ mastery (P =.007). There was a dose-dependent improvement in CRQ dyspnea scores (P <.05) with significant improvements only in the DM-training and DM-exposure groups. CONCLUSION: Exercise training substantially improved the impact of a dyspnea self-management program with a home walking prescription (DM). This impact tended to be dependent on the "dose" of exercise.