How Does Resorption Differ Among Single-Level and Multilevel Lumbar Disc Herniations? A Prospective Multi-Imaging and Clinical Phenotype Study.

STUDY DESIGN: Prospective, case series. OBJECTIVE: To identify and characterize any differences in specific patient factors, MRI findings, features of spontaneous disc resorption, and outcomes between patients with single-level and multilevel LDH. BACKGROUND: Lumbar disc herniation (LDH) is one of the most common spinal pathologies worldwide. Though many cases of LDH resolve by spontaneous resorption, the mechanism underlying this "self-healing" phenomenon remains poorly understood, particularly in the context of multilevel herniations. METHODS: A one-year prospective study was conducted of patients presenting with acute symptomatic LDH between 2017 and 2019. Baseline demographics, herniation characteristics, and MRI phenotypes were recorded before treatment, which consisted of gabapentin, acupuncture, and the avoidance of inflammatory-modulating medications. MRIs were performed approximately every three months after the initial evaluation to determine any differences between patients with single-level and multilevel LDH. RESULTS: Ninety patients were included, 17 demonstrated multilevel LDH. Body mass index was higher among patients with multilevel LDH ( P <0.001). Patients with multilevel LDH were more likely to exhibit L3/L4 inferior endplate defects ( P =0.001), L4/L5 superior endplate defects ( P =0.012), and L4/L5 inferior endplate defects ( P =0.020) on MRI. No other differences in MRI phenotypes ( e.g. Modic changes, osteophytes, etc .) existed between groups. Resorption rate and time to resolution did not differ between those with single-level and multilevel LDH. CONCLUSIONS: Resorption rates were similar between single-level and multilevel LDH at various time points throughout one prospective assessment, providing insights that disc healing may have unique programmed signatures. Compared with those with single-level LDH, patients with multilevel herniations were more likely to have a higher BMI, lesser initial axial and sagittal disc measurements, and endplate defects at specific lumbar levels. In addition, our findings support the use of conservative management in patients with LDH, regardless of the number of levels affected. LEVEL OF EVIDENCE: Level 3.

The impact of novel inflammation-preserving treatment towards lumbar disc herniation resorption in symptomatic patients: a prospective, multi-imaging and clinical outcomes study.

PURPOSE: We performed a prospective one-year multi-imaging study to assess the clinical outcomes and rate of disc resorption in acute lumbar disc herniation (LDH) patients undergoing inflammation-preserving treatment (i.e. no NSAIDS, steroids). METHODS: All patients received gabapentin to relieve leg pain, 12 sessions of acupuncture. Repeat MRI was performed, every 3 months, after 12 sessions of treatment continued for those without 40% reduction in herniated disc sagittal area. Disc herniations sizes were measured on sagittal T2W MRI sequences, pre-treatment and at post-treatment intervals. Patients were stratified to fast, medium, slow, and prolonged recovery groups in relation to symptom resolution and disc resorption. RESULTS: Ninety patients (51% females; mean age: 48.6 years) were assessed. Mean size of disc herniation was 119.54 ± 54.34 mm2, and the mean VAS-Leg score was 6.12 ± 1.13 at initial presentation. A total of 19 patients (21.1%) improved at the time of the repeat MRI (i.e. within first 3 months post-treatment). 100% of all patient had LDH resorption within one year (mean: 4.4. months). There was no significant difference at baseline LDH between fast, medium, slow, and prolonged resorption groups. Initial LDH size was weakly associated with degree of leg pain at baseline and initial gabapentin levels. Surgery was avoided in all cases. CONCLUSION: This is the first study to note inflammation-preserving treatment, without conventional anti-inflammatory and steroid medications, as safe and effective for patients with an acute LDH. Rate of disc resorption (100%) was higher than comparative recent meta-analysis findings (66.7%) and no patient underwent surgery.

Resorption of Lumbar Disk Herniation: Mechanisms, Clinical Predictors, and Future Directions.

INTRODUCTION: Resorption after lumbar disk herniation is a common yet unpredictable finding. It is hypothesized that nearly 70% of lumbar herniated nucleus pulposus (HNP) undergo the resorption to a significant degree after acute herniation, which has led to nonoperative management before surgical planning. METHODS: This narrative review on the literature from 4 databases (MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Scopus, and Cochrane) examines historical and recent advancements related to disk resorption. Studies were appraised for their description of the predictive factor (e.g., imaging or morphologic factors), pathophysiology, and treatment recommendations. OBSERVATIONS: We reviewed 68 articles considering the possibility of resorption of lumbar HNP. Recent literature has proposed various mechanisms (inflammation and neovascularization, dehydration, and mechanical traction) of lumbar disk resorption; however, consensus has yet to be established. Current factors that increase the likelihood of resorption include the initial size of the herniation, sequestration, percentage of rim enhancement on initial gadolinium-based magnetic resonance imaging (MRI), composition of inflammatory mediators, and involvement of the posterior longitudinal ligament. CONCLUSION: Heterogeneity in imaging and morphologic factors has led to uncertainty in the identification of which lumbar herniations will resorb. Current factors that increase the likelihood of disk resorption include the initial size of the herniation, sequestration, percentage of rim enhancement on initial MRI, composition of cellular and inflammatory mediators present, and involvement of the posterior longitudinal ligament. This review article highlights the role of disk resorption after herniation without surgical intervention and questions the role of traditional noninflammatory medications after acute herniation. Further research is warranted to refine the ideal patient profile for disk resorption to ultimately avoid unnecessary treatment, thus individualizing patient care.

Prediction of lumbar disc herniation resorption in symptomatic patients: a prospective, multi-imaging and clinical phenotype study.

BACKGROUND CONTEXT: Symptomatic lumbar disc herniations (LDH) are very common. LDH resorption may occur by a "self-healing" process, however this phenomenon remains poorly understood. By most guidelines, if LDH remains symptomatic after 3 months and conservative management fails, surgical intervention may be an option. PURPOSE: The following prospective study aimed to identify determinants that may predict early versus late LDH resorption. STUDY DESIGN/SETTING: Prospective study with patients recruited at a single center. PATIENT SAMPLE: Ninety-three consecutive patients diagnosed with acute symptomatic LDH were included in this study (n=23 early resorption and n=67 late resorption groups) with a mean age of 48.7±11.9 years. OUTCOMES MEASURE: Baseline assessment of patient demographics (eg, smoking status, height, weight, etc.), herniation characteristics (eg, the initial level of herniation, the direction of herniation, prevalence of multiple herniations, etc.) and MRI phenotypes (eg, Modic changes, end plate abnormalities, disc degeneration, vertebral body dimensions, etc.) were collected for further analysis. Lumbar MRIs were performed approximately every 3 months for 1 year from time of enrollment to assess disc integrity. METHODS: All patients were managed similarly. LDH resorption was classified as early (<3 months) or late (>3 months). A prediction model of pretreatment factors was constructed. RESULTS: No significant differences were noted between groups at any time-point (p>.05). Patients in the early resorption group experienced greater percent reduction of disc herniation between MRI-0-MRI-1 (p=.043), reduction of herniation size for total study duration (p=.007), and percent resorption per day compared to the late resorption group (p<.001). Based on multivariate modeling, greater L4 posterior vertebral height (coeff:14.58), greater sacral slope (coeff:0.12), and greater herniated volume (coeff:0.013) at baseline were found to be most predictive of early resorption (p<.05). CONCLUSIONS: This is the first comprehensive imaging and clinical phenotypic prospective study, to our knowledge, that has identified distinct determinants for early LDH resorption. Early resorption can occur in 24.7% of LDH patients. We developed a prediction model for early resorption which demonstrated great overall performance according to pretreatment measures of herniation size, L4 posterior body height, and sacral slope. A risk profile is proposed which may aid clinical decision-making and managing patient expectations.

Where do patients with MRI-confirmed single-level radiculopathy experience pain, and what is the clinical interpretability of these pain patterns? A cross-sectional diagnostic accuracy study.

Background: Clinicians nominate the distribution of leg pain as being important in diagnosing nerve root involvement. This study aimed to identify: (i) common unisegmental radicular pain patterns and whether they were dermatomal, and (ii) whether these radicular pain patterns assisted clinician discrimination of the nerve root level involved. Methods: A cross-sectional diagnostic accuracy study of adult patients with radicular leg pain at a hospital in Denmark. All patients had positive neurological signs (average 2.8 signs - hypoalgesia, diminished reflexes, muscle weakness, positive Straight Leg Raise test).Part 1 (pain patterns) was a secondary analysis of baseline pain pattern data collected during a clinical trial. The pain charts of 93 patients with an MRI and clinically confirmed single-level disc herniation with nerve root compression were digitised and layered to form a composite picture of the radicular patterns for the L5 and S1 nerve roots, which were then compared to published dermatomes.In Part 2 (clinical utility) we prospectively measured the discriminative ability of the identified pain patterns. The accuracy was calculated of three groups of six clinicians at classifying the nerve root affected in a randomized sequence of 53 patients, when not shown, briefly shown or continuously shown the composite pain patterns. In each group were two chiropractors, two medical doctors and two physiotherapists. Results: There was a wide overlap in pain patterns from compromised L5 and S1 nerve roots but some distinguishing features. These pain patterns had approximately 50 to 80% overlap with published dermatomes. Clinicians were unable to determine with any accuracy above chance whether an individual pain drawing was from a person with a compromised L5 or S1 nerve root, and use of the composite pain drawings did not improve that accuracy. Conclusions: While pain distribution may be an indication of radiculopathy, pain patterns from L5 or S1 nerve root compression only approximated those of sensory dermatomes, and level-specific knowledge about radicular pain patterns did not assist clinicians' diagnostic accuracy of the nerve root impinged. These results indicate that, on their own, pain patterns provide very limited additional diagnostic information about which individual nerve root is affected.

Four hundred or more participants needed for stable contingency table estimates of clinical prediction rule performance.

OBJECTIVES: To quantify variability in the results of statistical analyses based on contingency tables and discuss the implications for the choice of sample size for studies that derive clinical prediction rules. STUDY DESIGN AND SETTING: An analysis of three pre-existing sets of large cohort data (n = 4,062-8,674) was performed. In each data set, repeated random sampling of various sample sizes, from n = 100 up to n = 2,000, was performed 100 times at each sample size and the variability in estimates of sensitivity, specificity, positive and negative likelihood ratios, posttest probabilities, odds ratios, and risk/prevalence ratios for each sample size was calculated. RESULTS: There were very wide, and statistically significant, differences in estimates derived from contingency tables from the same data set when calculated in sample sizes below 400 people, and typically, this variability stabilized in samples of 400-600 people. Although estimates of prevalence also varied significantly in samples below 600 people, that relationship only explains a small component of the variability in these statistical parameters. CONCLUSION: To reduce sample-specific variability, contingency tables should consist of 400 participants or more when used to derive clinical prediction rules or test their performance.

SpineData - a Danish clinical registry of people with chronic back pain.

BACKGROUND: Large-scale clinical registries are increasingly recognized as important resources for quality assurance and research to inform clinical decision-making and health policy. We established a clinical registry (SpineData) in a conservative care setting where more than 10,000 new cases of spinal pain are assessed each year. This paper describes the SpineData registry, summarizes the characteristics of its clinical population and data, and signals the availability of these data as a resource for collaborative research projects. METHODS: The SpineData registry is an Internet-based system that captures patient data electronically at the point of clinical contact. The setting is the government-funded Medical Department of the Spine Centre of Southern Denmark, Hospital Lillebaelt, where patients receive a multidisciplinary assessment of their chronic spinal pain. RESULTS: Started in 2011, the database by early 2015 contained information on more than 36,300 baseline episodes of patient care, plus the available 6-month and 12-month follow-up data for these episodes. The baseline questionnaire completion rate has been 93%; 79% of people were presenting with low back pain as their main complaint, 6% with mid-back pain, and 15% with neck pain. Collectively, across the body regions and measurement time points, there are approximately 1,980 patient-related variables in the database across a broad range of biopsychosocial factors. To date, 36 research projects have used data from the SpineData registry, including collaborations with researchers from Denmark, Australia, the United Kingdom, and Brazil. CONCLUSION: We described the aims, development, structure, and content of the SpineData registry, and what is known about any attrition bias and cluster effects in the data. For epidemiology research, these data can be linked, at an individual patient level, to the Danish population-based registries and the national spinal surgery registry. SpineData also has potential for the conduct of cohort multiple randomized controlled trials. Collaborations with other researchers are welcome.

Rasch analysis of the 23-item version of the Roland Morris Disability Questionnaire.

OBJECTIVE: To determine the psychometric properties of the 23-item version of the Roland Morris Disability Questionnaire (RMDQ-23) and to quantify their stability across 2 cultures/languages and 2 types of care-settings. METHODS: Rasch analysis of data from 1,000 patients with low back pain from primary care (UK and Denmark) and secondary care (Denmark). RESULTS: The RMDQ-23 is unidimensional if local item dependency issues are accommodated, but contains several misfitting or overdiscriminating items, some poor targeting of items, and the scoring of 4-5 items is differentially affected by common clinical characteristics (such as age, gender, pain intensity, pain duration and care setting), depending on the country. CONCLUSION: As similar results have been found for the RMDQ-24, we believe it is timely to reconsider whether: (i) the RMDQ should be reconstructed using an item-response theory-based approach that includes consideration of new items and response options; or (ii) the use of alternative questionnaires should be recommended, such as the Oswestry Disability Index, that have shown evidence of fitting the Rasch model; or (iii) a completely new condition-specific questionnaire should be developed, perhaps utilizing a computerized adaptive testing platform.

The predictive ability of the STarT Back Screening Tool in a Danish secondary care setting.

INTRODUCTION: The predictive ability of the STarT Back Tool (SBT) in secondary care settings has not been investigated. The aim of this study was to determine the SBT's predictive ability in a Danish secondary care setting and compare this to a Danish primary care setting. METHODS: Poor clinical outcome at 6 months (>30 points on a 0-100 Roland Morris Disability Scale) was calculated in secondary care (n = 960) and primary care (n = 172) cohorts. The cohorts were stratified into SBT subgroups and estimates of additional risk for poor outcome were calculated [relative risk (RR), unadjusted and adjusted odds ratios]. The discriminative ability was determined using the area under the curve statistic. RESULTS: In secondary care 69.0 % and in primary care 40.2 % had poor outcome on activity limitation. Although significant, the predictive ability of the SBT in secondary care (medium-risk RR 1.5, high-risk RR 1.7) was not as strong as in primary care (medium-risk RR 2.3, high-risk RR 3.5). Adjusting for episode duration and pain intensity only changed the predictive ability marginally in secondary care. The discriminative ability of the SBT was similar in both cohorts despite differences in the predictive ability. CONCLUSION: The SBT had less predictive ability in a Danish secondary care setting compared to a Danish primary care setting for persistent activity limitation at 6 months follow-up. SBT-targeted treatment implications in secondary care were not investigated in this study.

Genotypic and antimicrobial characterisation of Propionibacterium acnes isolates from surgically excised lumbar disc herniations.

The anaerobic skin commensal Propionibacterium acnes is an underestimated cause of human infections and clinical conditions. Previous studies have suggested a role for the bacterium in lumbar disc herniation and infection. To further investigate this, five biopsy samples were surgically excised from each of 64 patients with lumbar disc herniation. P. acnes and other bacteria were detected by anaerobic culture, followed by biochemical and PCR-based identification. In total, 24/64 (38%) patients had evidence of P. acnes in their excised herniated disc tissue. Using recA and mAb typing methods, 52% of the isolates were type II (50% of culture-positive patients), while type IA strains accounted for 28% of isolates (42% patients). Type III (11% isolates; 21% patients) and type IB strains (9% isolates; 17% patients) were detected less frequently. The MIC values for all isolates were lowest for amoxicillin, ciprofloxacin, erythromycin, rifampicin, tetracycline, and vancomycin (≤1 mg/L). The MIC for fusidic acid was 1-2 mg/L. The MIC for trimethoprim and gentamicin was 2 to ≥4 mg/L. The demonstration that type II and III strains, which are not frequently recovered from skin, predominated within our isolate collection (63%) suggests that the role of P. acnes in lumbar disc herniation should not be readily dismissed.

Does nuclear tissue infected with bacteria following disc herniations lead to Modic changes in the adjacent vertebrae?

PURPOSE: To investigate the prevalence of infected herniated nucleus material in lumbar disc herniations and to determine if patients with an anaerobic infected disc are more likely to develop Modic change (MC) (bone oedema) in the adjacent vertebrae after the disc herniation. MCs (bone oedema) in vertebrae are observed in 6 % of the general population and in 35-40 % of people with low back pain. These changes are strongly associated with low back pain. There are probably a mechanical cause and an infective cause that causes MC. Several studies on nuclear tissue from herniated discs have demonstrated the presence of low virulent anaerobic microorganisms, predominantly Propionibacterium acnes, in 7-53 % of patients. At the time of a herniation these low virulent anaerobic bacteria may enter the disc and give rise to an insidious infection. Local inflammation in the adjacent bone may be a secondary effect due to cytokine and propionic acid production. METHODS: Patients undergoing primary surgery at a single spinal level for lumbar disc herniation with an MRI-confirmed lumbar disc herniation, where the annular fibres were penetrated by visible nuclear tissue, had the nucleus material removed. Stringent antiseptic sterile protocols were followed. RESULTS: Sixty-one patients were included, mean age 46.4 years (SD 9.7), 27 % female. All patients were immunocompetent. No patient had received a previous epidural steroid injection or undergone previous back surgery. In total, microbiological cultures were positive in 28 (46 %) patients. Anaerobic cultures were positive in 26 (43 %) patients, and of these 4 (7 %) had dual microbial infections, containing both one aerobic and one anaerobic culture. No tissue specimens had more than two types of bacteria identified. Two (3 %) cultures only had aerobic bacteria isolated. In the discs with a nucleus with anaerobic bacteria, 80 % developed new MC in the vertebrae adjacent to the previous disc herniation. In contrast, none of those with aerobic bacteria and only 44 % of patients with negative cultures developed new MC. The association between an anaerobic culture and new MCs is highly statistically significant (P = 0.0038), with an odds ratio of 5.60 (95 % CI 1.51-21.95). CONCLUSION: These findings support the theory that the occurrence of MCs Type 1 in the vertebrae adjacent to a previously herniated disc may be due to oedema surrounding an infected disc. The discs infected with anaerobic bacteria were more likely (P < 0.0038) to develop MCs in the adjacent vertebrae than those in which no bacteria were found or those in which aerobic bacteria were found.

The predictive and external validity of the STarT Back Tool in Danish primary care.

PURPOSE: The STarT Back Tool (SBT) was recently translated into Danish and its concurrent validity described. This study tested the predictive validity of the Danish SBT. METHODS: Danish primary care patients (n = 344) were compared to a UK cohort. SBT subgroup validity for predicting high activity limitation at 3 months' follow-up was assessed using descriptive proportions, relative risks, AUC and odds ratios. RESULTS: The SBT had a statistically similar predictive ability in Danish primary care as in UK primary care. Unadjusted relative risks for poor clinical outcome on activity limitation in the Danish cohort were 2.4 (1.7-3.4) for the medium-risk subgroup and 2.8 (1.8-3.8) for the high-risk subgroup versus 3.1 (2.5-3.9) and 4.5 (3.6-5.6) for the UK cohort. Adjusting for confounders appeared to explain the lower predictive ability of the Danish high-risk group. CONCLUSIONS: The Danish SBT distinguished between low- and medium-risk subgroups with a similar predictive ability of the UK SBT. That distinction is useful information for informing patients about their expected prognosis and may help guiding clinicians' choice of treatment. However, cross-cultural differences in the SBT psychosocial subscale may reduce the predictive ability of the high-risk subgroup in Danish primary care.

Antibiotic treatment in patients with chronic low back pain and vertebral bone edema (Modic type 1 changes): a double-blind randomized clinical controlled trial of efficacy.

PURPOSE: Modic type 1 changes/bone edema in the vertebrae are present in 6 % of the general population and 35-40 % of the low back pain population. It is strongly associated with low back pain. The aim was to test the efficacy of antibiotic treatment in patients with chronic low back pain (>6 months) and Modic type 1 changes (bone edema). METHODS: The study was a double-blind RCT with 162 patients whose only known illness was chronic LBP of greater than 6 months duration occurring after a previous disc herniation and who also had bone edema demonstrated as Modic type 1 changes in the vertebrae adjacent to the previous herniation. Patients were randomized to either 100 days of antibiotic treatment (Bioclavid) or placebo and were blindly evaluated at baseline, end of treatment and at 1-year follow-up. OUTCOME MEASURES: Primary outcome, disease-specific disability, lumbar pain. Secondary outcome leg pain, number of hours with pain last 4 weeks, global perceived health, EQ-5D thermometer, days with sick leave, bothersomeness, constant pain, magnetic resonance image (MRI). RESULTS: 144 of the 162 original patients were evaluated at 1-year follow-up. The two groups were similar at baseline. The antibiotic group improved highly statistically significantly on all outcome measures and improvement continued from 100 days follow-up until 1-year follow-up. At baseline, 100 days follow-up, 1-year follow-up the disease-specific disability-RMDQ changed: antibiotic 15, 11, 5.7; placebo 15, 14, 14. Leg pain: antibiotics 5.3, 3.0, 1.4; placebo 4.0, 4.3, 4.3. Lumbar pain: antibiotics 6.7, 5.0, 3.7; placebo 6.3, 6.3, 6.3. For the outcome measures, where a clinically important effect size was defined, improvements exceeded the thresholds, and a trend towards a dose-response relationship with double dose antibiotics being more efficacious. CONCLUSIONS: The antibiotic protocol in this study was significantly more effective for this group of patients (CLBP associated with Modic I) than placebo in all the primary and secondary outcomes.