bluuebunny/crossref_metadata_2025 huggingface dataset:
Baseline MRI Characteristics in Asymptomatic Subjects as Predictors for Future First-Time LBP Episode
Authors: Samartzis D. , Karppinen J. , Luk K. , Cheung K.
Published: June 2012

Introduction

Previously, it has been noted that there is no predictive value of MRI findings of degenerative changes of the lumbar spine in asymptomatic individuals in the development of first time episodes of low back pain (LBP). In a population-based cohort, this study addressed if radiographic findings on MRI in asymptomatic individuals are predictive in the development of first-time episodes of LBP and pain severity.

Materials and Methods

A prospective, radiographic and clinical study was performed in 248 asymptomatic individuals of Southern Chinese origin with no previous history of LBP. All subjects underwent sagittal MRI assessment of the lumbar spine. Assessment of disk degeneration was based on the Schneiderman et al radiographic criteria to determine the presence, extent, and severity of disk degeneration. A summated degenerative disk disease (DDD) score of the lumbar spine was obtained, representing the global severity of disk degeneration. The presence of disk bulge/extrusion, Schmorl's nodes (SN), and Modic changes were also noted. At 2 years minimum follow-up, clinical assessment was performed and subject demographics were noted to identify the development of LBP and functional outcome status (e.g., Oswestry disability index).

Results

There were 93 males and 155 females with a mean age at MRI of 42.9 years ( ± SD = 7.6, range: 21.1 to 54.6 years). Overall presence of disk degeneration, disk space narrowing, and disk bulge/extrusion was noted in 60.5, 19.0, and 34.3% of individuals, respectively. The mean DDD score was 2.2 ( ± SD = 2.9; range: 0 to 12). SN and Modic changes were noted in 10.5 and 1.2%, respectively. Clinical follow-up was performed at a mean of 4.3 years ( ± SD = 1.9, range: 2.2 to 10.0 years). The incidence rate of first-time LBP episodes on clinical follow-up was 34.7%. The mean age of first-time LBP episode was 44.8 years ( ± SD = 8.5; range: 22 to 57 years). Regression modeling noted that the presence of disk bulge/extrusion (OR: 2.37; 95% CI, 1.30–4.32) and increasing DDD score (>7 score OR: 6.90; 95% CI, 1.86–25.52), in particular if segments involved the mid lumbar region, demonstrated significant predictive utility for developing first-time LBP episode. DDD score and disk bulge/extrusion were found predictive to the severity of LBP, greater functional disability, and increased frequency of future LBP episodes ( p < 0.05).

Conclusion

This large-scale prospective study substantiates that spinal changes are found in asymptomatic subjects on MRI; however, the “global severity” of disk degeneration on initial MRI may be predictive in the development of first-time LBP episodes. I confirm having declared any potential conflict of interest for all authors listed on this abstract No Disclosure of Interest None declared
Predictors of Sickness Absence in Patients with a New Episode of Low Back Pain in Primary Care
Authors: Melloh M. , Rolli Salathé C. , Käser A. , Elfering A.
Published: June 2012

Introduction

Although there is a call for early risk prediction of sickness absence, specific prognostic factors of low back pain (LBP) related sickness absence have not yet been established in either clinical or research settings. This study examines predictors of sickness absence in patients presenting to a health practitioner with acute/subacute LBP. The aims of our study were twofold: (1) To identify baseline variables that detect patients with a new LBP episode at risk of sickness absence; and (2) To identify prognostic models for sickness absence at different time points after initial presentation.

Materials and Methods

Prospective cohort study investigating 310 patients presenting to a health practitioner with a new episode of LBP at baseline, 3-, 6-, 12-week, 6-month follow-up, addressing work-related, psychological, and biomedical factors. Multivariate logistic regression analysis was performed to identify baseline predictors of sickness absence at different time points.

Results

The best prognostic model comprised “job control”, “depression,” and “functional limitation” as predictive baseline factors of sickness absence at 6-week follow-up (sensitivity 43.5; specificity 96.5; overall predictive value 89.0) with “job control” being the best single predictor (OR 0.49; 95% CI, 0.27–0.89). This model explained 46% of variance of sickness absence at 6-week follow-up ( p < 0.001). The second best model included “job control” (OR 0.64; 95% CI, 0.42–0.96) as the only significant predictive baseline factor for sickness absence at 3-week follow-up (sensitivity 45.2; specificity 94.7; overall predictive value 83.9). This model explained 39% of variance of sickness absence ( p < 0.001). Sickness absence at a time point beyond 6 weeks could not be predicted.

Conclusion

For patients with acute/subacute LBP, the model has the greatest predictive ability for sickness absence at 6 weeks after initial presentation to a health practitioner. The prediction of sickness absence beyond 6 weeks is limited, and health practitioners should re-assess patients at 6 weeks, especially if they have previously been identified as at risk of sickness absence. This would allow timely intervention with measures designed to reduce the likelihood of prolonged sickness absence. Further research is warranted investigating assessment at different time points, to identify the optimal time at which to reassess at risk acute/subacute LBP patients to accurately predict sickness absence. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared
Who is Likely to Develop Persistent Low Back Pain? a Longitudinal Analysis of Prognostic Occupational Factors
Authors: Melloh M. , Käser A. , Rolli Salathé C. , Elfering A.
Published: June 2012

Introduction

Socioeconomic costs of persistent low back pain (LBP) exceed the costs of acute and subacute LBP by far. This makes the early identification of patients at risk of developing persistent LBP essential. By differentiating risk from protective factors, these factors could be addressed proactively to limit the associated socioeconomic burden. Aim of our study was to identify factors influencing the progression of acute/subacute LBP to the persistent state.

Materials and Methods

This is a prospective cohort study of patients attending a health practitioner for their first episode of acute/subacute LBP. Patients were assessed at baseline addressing occupational, psychological, biomedical, and demographic/lifestyle factors and followed up over 6 months according to the recommendations from the Multinational Musculoskeletal Inception Cohort Study (MMICS) Statement. Multivariate logistic regression analysis was performed separately for the variables groups of the four different domains, controlling for age, gender, and body mass index. The overall predictive value was calculated for the full regression models of the different domains. Finally, all significant variables from the different domains were combined into a final predictor model.

Results

The final four-predictor model predicted 51% of variance of persistent LBP and included “resigned attitude towards the job” (OR 1.73; 95% CI, 1.16–2.59), “social support at work” (OR 0.54; 95% CI, 0.32–0.90), “functional limitation” (OR 1.05; 95% CI, 1.01–1.10), and “duration of LBP” (OR 1.04; 95% CI, 1.02–1.06). The accuracy of the model was 83%, with 92% of nonpersistent and 67% of persistent LBP patients correctly identified.

Conclusion

In this study of patients with acute/subacute LBP, “resigned attitude towards the job” increased the likelihood of persistent LBP at 6 months. Addressing this factor with workplace interventions has the potential to modify the outcome. “Social support at work” was a protective factor meaning that development of persistent LBP was less likely. It can therefore be considered as a resource for prevention of persistent LBP. Findings from this study confirm the requirement for measurement of occupational factors in screening tools for patients at risk of developing persistent LBP. Further research is required to investigate different types of social support at work regarding their prognostic influence on the development of persistent LBP. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared
Expression and Distribution of Interleukin-17 in Degenerated Human Cervical Intervertebral Disks
Authors: Zhang Y.
Published: June 2012

Introduction

To investigate the expression and distribution of interleukin-17 (IL-17) ingenerate human cervical intervertebral disks tissues and to explore the relationship between IL-l7 and cervical intervertebral disk degeneration.

Materials and Methods

IL-Iβ,IL-17,tumor necrosis factor (TNF-α), and retinoid-related orphan receptor (RORγt) mRNA levels were respectively measured by real-time quantitative reverse transcription-polymerase chain reaction (QT-PCR) in 30 surgical degenerate cervical intervertebral disk tissues (degeneration group) and 10 nondegenerate control tissues (control group). The level of IL-17 protein and CD4 cell surface antigen were measured by immunohistochemistry staining.

Results

The mean IL-1β, IL-17, TNF-α, RORγt mRNA levels in degeneration group were significantly higher than that in control group( p < 0.001),and the expression of these factors in nucleus pulposus were significantly higher than that in annulus fibrosus (AF) in degeneration group( p < 0.05). The expression level of IL-17 mRNA was positively correlated with RORγt mRNA level ( r = 0.61, p < 0.001). Immunoreactivity of IL-17 and CD4 cell surface antigen were significantly greater in degenerate disks than in controls ( p < 0.001),and the immunoreactivity in nucleus pulposus was higher than that in AF in degeneration group( p < 0.05).

Conclusion

The expression level of IL-17 mRNA and IL-17 protein were significantly increased in degenerate human cervical disk tissues than that in autopsy control tissues, and the expression in nucleus pulposus was greater than in AF. These findings suggest involvement of IL-17 in the pathomechanism of intervertebral disk degeneration. Immune inflammation mediated by Th17 lymphocytes may play an important role in the development and progression of human cervical intervertebral disk degeneration. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared
Is the Morphology and Size of Schmorl's Nodes of the Lumbar Spine Related to Severity of Disk Degeneration?
Authors: Samartzis D. , Mok F. , Karppinen J. , Luk K. , Cheung K.
Published: June 2012

Introduction

We have recently confirmed that the presence of Schmorl's nodes (SN) was highly associated with disk degeneration in a large population-based cohort study in Southern Chinese. Based on our previous proposed classification system of SN, we attempt to further address the association of SN characteristics and the severity of disk degeneration.

Materials and Methods

Two independent observers assessed sagittal T2-weighted MRIs of the lumbar spine ( n = 2449) for the presence and characteristics of SN, and additional radiologic features. The patterns of SN characteristics were assessed by hierarchical clustering methods. Generalized linear models were used to assess the associations of the shape and size of SN with disk degeneration severity.

Results

Total 401 subjects with SN (16.4%) were included in the analysis. Hierarchical clustering showed that typical SN were usually smaller in size with shape type I to III (i.e., indented endplate, sharp or rounded shape) whereas atypical SN were larger with shape type IV to V (i.e., rectangular or irregular shape). Total 8.3% of all identified SN ( n = 960) were atypical SN. Multivariate ordinal logistic regression adjusted for gender, age, body mass index, smoking status, presence of disk bulge/extrusion, and high intensity zone showed that atypical SN and typical SN, depending on the lumbar levels, were associated with 5- to 13-fold and 2- to 4-fold higher risk of increased severity of disk degeneration, respectively ( p < 0.05).

Conclusion

This was the first study to address the relationships of SN morphology to the severity of disk degeneration. The associations of SN morphology with disk degeneration severity might be clinically relevant. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared
Inhibiting Brain-Derived Neurotrophic Factor (Bdnf) at the Punctured Intervertebral Disk Downregulates Pain-Related Neuropeptide Production in Dorsal Root Ganglia in Rats
Authors: Orita S. , Eguchi Y. , Inoue G. , Yamauchi K. , Ishikawa T. , Miyagi M. , Kamoda H. , Arai G. , Suzuki M. , Sakuma Y. , Oikawa Y. , Kubota G. , Inage K. , Takahashi K. , Ohtori S.
Published: June 2012

Introduction

BDNF-a neurotrophin in dorsal root ganglion (DRG) neurons-is known to be anterogradely transported to the spinal cord and transmits pain signals existing in the central nervous system. A previous study has recently reported its presence in the peripheral sites of degenerative IVDs, although its association with discogenic pain remains unclear. The present study aimed to investigate the association between BDNF and pain-related sensory innervation of multiple-punctured lumbar IVD in rats.

Materials and Methods

Forty female Sprague-Dawley rats were equally divided into four groups: naïve, sham, and two agent-treated groups (vehicle (saline-treated) and anti-BDNF (anti-BDNF antibody) group). L5-6 IVDs of the agent-treated rats were exposed and injured by repeated punctures. The retrograde neurotracer Fluoro-Gold (FG) and treatment agents were intradiscally applied. In the sham group, FG alone was applied onto uninjured IVD. One week later, L1-3 DRGs were harvested and immunolabeled for the inflammatory pain-related calcitonin gene-related peptide (CGRP), that is, the pain marker. The proportions of FG-labeled CGRP-immunoreactive (-ir) DRG neurons were assessed. BDNF concentration of each L5-6 IVD was measured using enzyme-linked immunosorbent assay (ELISA).

Results

FG-labeled DRG neurons were almost equally prevalent at each DRG level. The proportions of FG-labeled CGRP-ir DRG neurons in the two agent-treated groups were significantly elevated ( p < 0.05) compared with the naïve and sham groups and were significantly decreased in the anti-BDNF group as compared to the vehicle group ( p < 0.05). BDNF concentrations were elevated maximally in the vehicle group but suppressed in the anti-BDNF group.

Conclusion

Direct intradiscal application of the anti-BDNF antibody significantly suppressed both CGRP production and the local concentration of BDNF. Our results indicate a possible association between the local production of BDNF and the pathophysiology of discogenic pain. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared
Chronic Unpredictable Stress Induces Intervertebral Disk Cell Apoptosis and Degeneration
Authors: Reihani Kermani H. , Hobubati H. , Esmaeili Mahani S. , Assadi Shekari M.
Published: June 2012

Introduction

Animal model was used to study the effects of chronic unpredictable stress (CUS) on the intervertebral disk (IVD). Stress is a predictor for low back disability in persons with earlier low back pain (LBP) and LBP is most common in the early stages of IVD degeneration. Stress can increase proinflammatory cytokines. Elevated levels of molecular mediators of inflammation have been described in the pathology of IVD degeneration; however, the effect of chronic stress on the induction of disk degeneration has not yet been clarified.

Materials and Methods

Cellular events involved in injury-and stress-induced disk degeneration in male Wistar rats were investigated. Disk degeneration and apoptosis was evaluated by microscopic (light and electron) and molecular (immunoblotting and immunohistochemistry) methods. Corticosterone levels were measured by radioimmunoassay as a marker of stress condition.

Results

The data showed that chronic stress could significantly increase corticosterone levels. Furthermore, biochemical markers of apoptosis (increased Bax to Bcl2 ratio ( p < 0.05) and TUNEL reactivity) were observed in animals that had chronic stress. Electron and light microscopy also showed disk degeneration and apoptotic cells in over experimental group.

Conclusion

Taken together, the data demonstrated that chronic stress is probably a risk factor for creating IVD degeneration and that programmed cell death is one of the mechanisms of stress-induced disk degeneration, however, the effects of stress and its impact on the escalation of disk degeneration and LBP need to be clarified by further investigations. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared
Optimizing Oxygenation and Serum Concentration in Ex Vivo Culture of Mouse Nucleus Pulposus Cells Derived from the Notochord
Authors: Nakajima D. , Sakai D. , Tanaka M. , Yokoyama K. , Hiyama A. , Mochida J.
Published: June 2012

Introduction

It has been a long-time argument regarding the origin of NP cells in adult humans. Recent review on lineage studies suggests that all nucleus pulposus cells including chondrocyte-like cells are derived from notochordal precursors and those variations in morphology and size are representative of different stages of maturation, and or, function. To define fate of cells in the IVDs that originate from the notochord, we investigated the IVDs of double-transgenic (TG) mouse encoding Protein-0(P0)-Cre/Floxed-EGFP. Cells originating from the neural crest or notochord express positivity for GFP in this TG mouse. We analyzed the effect of hypoxia and serum concentration in notochordal NP cells.

Materials and Methods

The double transgenic P0-Cre/Floxed-EGFP mice ( n = 10, 5–7 Wks old) were used. The NP cells were isolated from the coccygeal IVDs of P0-Cre/Floxed-EGFP mouse under microscopy and cultured for 10 days without enzymatic processing. After passage these cells were divided into four groups according to the culture condition, Group A; Hypoxia (2% O2) and 20% FBS, Group B; Hypoxia and 10% FBS, Group C; Normoxia (21% O2) and 20% FBS, Group D; Normoxia and 10% FBS. These cells are cultured for over 7 days. We evaluated cell counts with trypan blue staining, cell cycle, and apoptosis by the flow cytometry on the third, fifth, and the seventh day of culture.

Results

The cell number in group A after the seventh day of culture showed the obviously largest increase. On the seventh day the cell number in group A showed a 17-fold increase, group B showed a 9-fold increase, group C showed a 2-fold increase, group D showed a 1.8-fold increase. The hypoxia (2% O2) groups showed increased cell proliferation rate than the normoxia (21% O2) groups, and the higher FBS concentration (20%) groups showed increased cell proliferation than the lower FBS (10%) groups. Though it seems that in GFP positive and negative ratio there is a difference between the hypoxia groups and the normoxia groups, it has not said clearly yet. We need to obtain some more number of culture. There were no significant changes in the cell cycle and apoptosis between these groups.

Conclusion

The condition of a low oxygen density and higher FBS concentration was the optimized condition for the mouse notochordal NP cells. Since notochordal NP cells may be important for NP tissue maintenance and phenotype, our result will be useful in ex vivo investigations and based therapy for disk disease. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared
Human Intervertebral Disk Degeneration is Associated with Increased Chemokine Expression
Authors: Phillips K. L. E. , Chiverton N. , Haddock G. , Bunning R. , Cross A. , Le Maitre C.
Published: June 2012

Introduction

Within the avascular intervertebral disk (IVD) local cells are considered autologous regulators of cellular function. Previously cytokine expression, particularly IL-1 and TNF1,2, has been identified and associated with both homeostatic mechanisms and the pathogenesis of IVD degeneration. To date little is known of chemokine expression within the human IVD and here we investigated the hypothesis that an altered chemokine expression profile is associated with IVD degeneration.

Materials and Methods

Expression of 11 chemokine and 6 associated receptor genes was investigated using qRT-PCR in human IVD samples from nondegenerate and degenerate study groups. Immunohistochemistry was used to localize protein production of certain chemokines and to relate this to the observable grade of degeneration in human IVD tissue.

Results

Altered gene expression patterns of chemokines and their receptors were observed between nondegenerate and degenerate groups including; upregulation of CCL3 (Fig. 1A) and downregulation of CX3CL1 in degeneration, and upregulation of receptors CCR1, CXCR1, and CXCR2 in degeneration. Protein expression of IL-16, CCL2, CCL3 (Fig. 1B), CCL4, CCL7, and CXCL8 was localized to nucleus pulposus cells and CCL2, CCL3 (Fig. 1C), and CXCL8 expression was seen to correlate with the observable grade of tissue degeneration.

Conclusion

This study demonstrates the altered gene expression patterns of certain chemokines and their receptors in human IVD degeneration and the positive correlation between expression of certain chemokines and characteristic signs of IVD degeneration. This suggests chemokines may be involved in the pathogenesis of IVD degeneration. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared Le Maitre et al., (2005) Arthritis Research & Therapy. 7, R732-R745 Le Maitre et al., (2007) Arthritis Research & Therapy. 9, R77
Intervertebral Disk Degeneration in the Growing Spine in Patients with Tuberculosis Kyphosis Exceeding 50 Treated by Reconstruction with a Long-Length Posterior Instrumentation
Authors: Pershin A. A. , Mushkin A. Y.
Published: June 2012

Introduction

The rigid angular kyphoses in the young patients with spinal TB are not only a cosmetic problem, they also lead to cardiovascular, respiratory, and neurological disorders. The correction of the deformity could be reached by combination of the debridement, anterior column reconstruction, the shortening of posterior spine, and extended posterior instrumentation. The zone of instrumentation needs to be longer than the anterior fusion for significant correction and spinal stability.

Materials and Methods

Total 13 children from 2.5 to 12 years with TB spondylitis of the thoracic and lumbar spine complicated by severe angular kyphosis underwent 1-day combined surgery included anterior debridement followed by cortical bone allografting and posterior osteotomy with correction and instrumentation by laminar or hybrid devises. The anterior reconstruction exceeded three segments in all cases (maximum-replacement of 10 vertebral bodies). For real deformity correction the posterior instrumented zone exceeded the length of anterior reconstruction up to 1 or 3 segments cephalad and caudad. The operations were performed under the SSEP monitoring and additionally with wake-up test-in older cases. Neither neurological nor inflammatory complications were in these patients. The normal or closed to the normal sagittal profile was reached in all cases. Follow-up period ranged from 2 till 13 years. Complete follow-up: 13 cases. All patients have annual X-ray control. There wasn't any signs of anterior pseudo-arthrosis revealed. The condition of subchondral vertebral plates and the height of intact intervertebral disks within the zone of instrumentation and disks adjacent to the instrumented spine were compared.

Results

Total 11 of 13 operated patients (85%) demonstrated degeneration of initially intact disks within the instrumented spine 2 years after the surgery. The signs included loss of disk height, sclerosis, and deformation of subchondral vertebral plates. Despite nobody had back pain, the main parents' complaint was the limitation of spine range of motion. We've decided to count the early symptoms of disk degeneration, the indication to remove spinal hardware having solid anterior fusion documented. There was no increase of kyphosis, excluding one case of conjunctive deformity above the instrumented spine.

Conclusion

The intervertebral disks degeneration within the instrumented zone is a typical side effect of prolonged posterior rigid instrumentation in growing spine. After 2 years of surgery, it occurred in a majority of pediatric patients who had been operated due to the thoracic and lumbar spinal TB complicated by kyphosis exceeded 50ø. This degeneration was not accompanied by the pain during the childhood, but it may become symptomatic in adulthood. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared
Body Mass Index and Smoking Predict Lumbar Disk Degeneration among Young Finnish Males
Authors: Takatalo J. , Karppinen J. , Taimela S. , Niinimäki J. , Laitinen J. , Blanco Sequeiros R. , Paananen M. , Remes J. , Näyhä S. , Tammelin T. , Korpelainen R. , Tervonen O.
Published: June 2012

Introduction

The role of environmental factors in lumbar intervertebral disk degeneration (DD) in young adults is largely unknown. Therefore, we investigated whether body mass index (BMI), smoking, and physical activity are associated with lumbar DD among young adults.

Materials and Methods

The study population, Oulu Back Study (OBS), belongs to the 1986 Northern Finland Birth Cohort (NFBC 1986), consisting originally of 9479 children. Of 2969 eligible cohort members, 1987 subjects answered to a survey at the mean age of 18. Of these, 874 participated in physical examination at the mean age of 19 and were invited to lumbar MRI study. A total of 558 young adults (325 females and 233 males) underwent MRI that used a 1.5-T scanner at the mean age of 21. Each lumbar intervertebral disk was graded as normal (0), mildly (1), moderately (2), or severely (3) degenerated. We calculated a sum score of the lumbar DD, and analyzed the associations between environmental risk factors and DD using ordinal logistic regression. In the univariate models, the determinants included pack-years of smoking at 19 years, mean level of physical activity in metabolic equivalent hours per week at 16 and 19 years, body mass index (BMI), weight, height and waist circumference (WC) at 16 and 19 years. Because of collinearity, only one weight-related factor was included in the multivariate model. All analyses were stratified by gender.

Results

Of the 558 subjects, 257 (46%) had no DD, 117 (21%) had sum score of one, 93 (17%) sum score of two, 43 (8%) sum score of three, and 49 (8%) sum score of four or higher. In the univariate analyses, BMI, height, weight, and WC at 16 and 19 years were associated with DD among males. Among females, height at 16 and 19 years was associated with DD. Smoking of at least four pack-years was associated with DD among males. In the multivariate model, BMI at 16 years was associated with DD sum score among males (OR 2.35; 95% CI, 1.19–4.65) but not among females (OR 1.29; 95% CI, 0.72–2.32). Smoking of at least four pack-years tended to be associated with DD among males, but not among females (OR 2.41; 95% CI, 0.99–5.86 and 1.59; 95% CI, 0.67–3.76, respectively). Level of physical activity was not associated with DD.

Conclusion

BMI at 16 years and 19 years predicted lumbar DD at 21 years among young males whereas no associations were found among females. Smoking of at least four pack-years tended to be associated with DD among males. These results suggest that environmental factors are associated with DD among young males. I confirm having declared any potential conflict of interest for all authors listed on this abstract No Disclosure of Interest None declared
Surgical Soft Tissue Trauma Can Cause Disk Degeneration—An in Vivo Animal Study on Goettingen Minipigs
Authors: Omlor G. , Huettner F. , Lorenz S. , Holschbach J. , Richter W. , Gühring T.
Published: June 2012

Introduction

Biological treatment options, such as disk-cell-therapy, have been proposed for only moderately degenerated disks. Therefore, surgical exposition of the disk is needed. However, the effect of surgery related soft-tissue damage on the maintenance of disk degeneration is poorly understood. Therefore, this study analyzes, if disk degeneration can be induced only by the surgical approach.

Materials and Methods

We used an established model with adult minipigs offering biomechanical properties similar to humans. Total 12 animals underwent surgery using an anterolateral retroperitoneal approach to the lumbar spine. At each animal, two disks were only exposed whereas two other disks were exposed and partially nucleotomized with a 16G-biopsy-needle. Animals received a second revision surgery after 12 weeks, using the same approach and all disks were exposed again. Total 13 or 24 weeks after first surgery, animals were sacrificed. Disk height was measured in the central part of the disk by micro-CT. Disk degeneration was evaluated by a semiquantitative histo-degeneration-score. Three untreated control animals served as controls.

Results

After the second surgery, increased scar tissue and less vascularization was found around the lumbar vertebral bodies on the side of the approach. Most degenerative changes were found after partial nucleotomy ( p < 0.05) and additional annular damage was detectable, with a trend to higher degeneration scores after 24 weeks; disk height was significantly reduced compared to all other groups ( p < 0.05; 3.2 and 3.3 mm). Disks that were only surgically exposed also revealed significant degenerative changes including increased osteophytes; disk height was also significantly reduced compared to healthy control disks from animals without surgery ( p < 0.05; 3.7 and 3.8 mm vs. 4.6 mm).

Conclusion

Surgical exposure of lumbar disks caused significant disk degeneration without further disk manipulations. Reduced nutrient supply to the disk caused by less vascularized scar tissue seems to be a reason, which will be analyzed by additional immunohistological stainings against CD31. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared
Retrograde Vertebral Bone Drilling-How does it Influence Vertebral Endplates and the Course of Disk Degeneration?
Authors: Omlor G. , Huettner F. , Lorenz S. , Holschbach J. , Richter W. , Gühring T.
Published: June 2012

Introduction

Retrograde extra-articular bone drilling is a common procedure in orthopaedic surgery and offers good results in the therapy of osteochondral defects. It induces an inflammatory reaction in the bone underneath cartilage defects leading to decompression, revascularization, and consequent cartilage healing. For the treatment of disk degeneration or injury such an approach has not been tested so far. Therefore, the goal of this study was to evaluate if retrograde extra-articular drilling can be transferred to the lumbar motion segment consisting of subchondral bone, vertebral endplate, and the disk.

Materials and Methods

We used an established porcine disk degeneration model. To induce disk degeneration, 12 animals received surgery over an anterolateral approach to pierce the annulus and perform a partial nucleotomy in a total of 48 lumbar disks. Total 24 disks served as internal controls. After 12 weeks, all nucleotomized disks were degenerated and a second surgery was done to perform retrograde drilling of the vertebral bone in 24 of the nucleotomized disks using a customized drilling device. Drilling was stopped at the vertebral endplate, to avoid additional endplate and disk damage. Animals were sacrificed 13 or 24 weeks after the first surgery.

Results

Drilling was accurate and reproducible, but five disks had to be excluded because vertebral endplates were reached with possible endplate damage. Compared to segments only nucleotomized, additional drilling did not cause statistically significant morphometric changes to the adjacent subchondral vertebral bone of the endplates in micro-CT-analysis ( p > 0.05 for BV/TV and trabecular thickness). Disks from both groups showed equal disk height reduction, compared to internal controls and disk degeneration was not significantly different in segments with additional drilling (semi-quantitative histo-degeneration-score). Osteophytes were increased.

Conclusion

Retrograde bone drilling underneath the vertebral endplate did not result in disk regeneration or a limitation of the degeneration process induced by annular damage and partial nucleotomy. Contrary to articular cartilage, the degenerated disk may not be treatable by retrograde bone drilling. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared
Micromorphological Investigations of Intervertebral Disk Degeneration using Electron Microscopy
Authors: Friedmann A. , Schwan S. , Goehre F. , Heilmann A. , Meisel H. J.
Published: June 2012

Introduction

Intervertebral disk (ID) degeneration can be distinguished by various changes in the tissue structure like delamination and crack formation of the collagenous matrix as well as cellular changes like cell aging and variances in the amount and allocation of the cells. These indications of ID degeneration are shifting while increasing grade of degeneration. It has been confirmed that the ultrafine structure of disk tissue significantly influence the disk stability. Conventional clinical imaging techniques like CT and MRI are not able to visualize tissue morphology and tissue damages on this structure level.

Materials and Methods

To get detailed information about the degeneration and to achieve deeper insights into the morphology and microstructure of disk tissue, samples are investigated by scanning electron microscopic (SEM) techniques with corresponding sample preparations. The method allows the determination of the tissue morphology at high resolution. During this study, sequester material, achieved by standard sequestrectomy of 48 patients of different grades of degeneration, has been investigated.

Results

In the extracted tissue, we visualize different regions with characteristic microstructural damage behaviors, such as regions of prevalent micro cracks, or regions of fiber matrix delamination or fiber bridging. Furthermore, variations in cell density and cell morphology conditioned by the grade of degradation have been analyzed. Identified microstructural characteristics are correlated with MRI-based clinical rating scale for degeneration.

Conclusion

Investigations of degeneration characteristics of ID tissues by SEM propose high resolved analysis of both the tissue structure and the cell morphology. Correlation of the gleaned data regarding studies and classifications like Thompson scale shows a diffuse incidence of degeneration characteristic. The estimation of the grade of ID tissue degeneration, only by date achieved from MRI, is insufficient to appoint tissue-specific grade of degeneration. It is necessary to develop a new rating system considering variances within the tissue macro- and micromorphology as well as MRI data. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared
Genetic Association Studies in Lumbar Disk Degeneration: A Systematic Review
Authors: Eskola P. J. , Lemmelä S. , Kjaer P. K. , Solovieva S. , Männikkö M. , Tommerup N. , Lind-Thomsen A. , Husgafvel-Pursiainen K. , Cheung K. M. , Chan D. , Samartzis D. , Karppinen J.
Published: June 2012

Introduction

Low back pain (LBP) is one of the most disabling conditions associated with substantial socioeconomic and health care consequences. LBP is associated with lumbar disk degeneration, which is mainly accounted for genetic predisposition. The objective was to perform a systematic review to assess the level of evidence of polymorphisms associated with lumbar disk degeneration as defined on magnetic resonance imaging (MRI) in humans, evaluate study methods and findings to facilitate further efforts, and assess the clinical relevance of current information.

Materials and Methods

We performed a systematic literature search on MEDLINE, MEDLINE In-Process, SCOPUS, ISI Web of Science, The Genetic Association Database, and The Human Genome Epidemiology Network for information published between 1990 and 2011 addressing genes and lumbar disk degeneration. Two investigators independently identified studies to determine inclusion and study selection, and to perform data extraction, which consisted of study characteristics, population structure, phenotypes, genotyping details, possible biases, and significance of the association results.

Results

Total 52 studies were included for review. Total 48 studies reported at least one positive association between a genetic marker and lumbar disk degeneration. Level of evidence for the genetic associations was analyzed according to The HuGENet Working Group guidelines. Phenotype definition of lumbar disk degeneration was highly variable between the studies and replications were inconsistent. Most of the associations presented with weak level of evidence. Due to the heterogeneity between studies, meta-analyses could not be justified. The level of evidence was moderate for ASPN (D-repeat), COL11A1 (rs1676486), GDF5 (rs143383), SKT (rs16924573), THBS2 (rs9406328), and MMP9(rs17576).

Conclusion

Based on this first extensive systematic review on the topic, the credibility of reported genetic associations is mostly weak. Phenotype definitions of disk degeneration were inconsistent in studies, which impeded meta-analysis. Clear definition of lumbar disk degeneration and large population-based cohorts are needed. An international consortium is needed to establish standardization of genetic association studies in relation to disk degeneration. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared
Does Erythropoietin and Its Receptor may Play a Role in Human Intervertebral Disk Degeneration?
Authors: Grasso G. , Certo F. , Pirrone A. G. , Iacopino D.
Published: June 2012

Introduction

Degeneration of lumbar intervertebral discs is considered to be a cause of low back pain and radiculopathy. Many studies have shown that intervertebral disk inflammation and axonal growth of afferent fibers innervating the disk degeneration have a principal role in this pathological process. Both mechanical compression and chemical factors within nucleus pulposus (NP) are associated with the occurrence of radiculopathy. NP contains various proinflammatory cytokines that play important roles in the chemical pathogenesis of NP-induced peripheral nerve injury. The proinflammatory cytokine tumor necrosis factor alpha (TNF-α) is a key trigger in the pathogenesis of NP-induced inflammation and apoptosis and its inhibition can reduce NP degeneration. A class of MAPKs and p38 MAPK is phosphorylated by stress signals such as inflammatory cytokineso, smotic shock, and ischemia. Spinal cord and peripheral nerve injury cause the activation of p38 in dorsal root ganglion (DRG) neurons and spinal cord microglia. Furthermore, TNF-α phosphorylates p38 and activated p38 MAPK upregulates the biosynthesis of TNF- α. TNF and p38 are involved in neuronal cell apoptosis in peripheral nerve injuries. Erythropoietin (EPO) is a pleiotropic cytokine originally identified for its role in erythropoiesis. Recent studies have demonstrated that EPO and its receptor (EPO-R) are expressed in the central nervous system, where EPO exerts neuroprotective functions.

Materials and Methods

The aim of the present study was to investigate whether the resident EPO and EPO-R network is present and functional in the NP of intervertebral disk in different grade of degeneration. In this study, we analyzed 20 human NP obtained following microdiscectomy. The expressions of p-p38, TNF- α, EPO, and EPOR were assessed by immunohistochemical and immunoblotting analysis. Data were analyzed by unpaired Student t-test and Dunnett t-test (significance level, p < 0.05).

Results

In barely degenerated disk, significantly weak expression of EPO and EPO-R was observed ( p < 0.05). Accordingly, the expression of both p-p38 and TNF in the NP was significantly lower than in well-degenerated disk ( p < 0.05). In clearly degenerated disc, a marked increase of expression of EPO and EPO-R was observed ( p < 0.05) and a consensual increase of both p-p38 and TNF in the NP was observed ( p < 0.05).

Conclusion

These observations suggest that the local EPO and EPO-R system is markedly engaged in the degeneration of intervertebral disk by a feasible cross-talk with network of proinflammatory cytokine such as TNF- α. These data may increase our knowledge on mechanisms underlying intervertebral disk degeneration and strongly support the possible usefulness of a therapeutic approach based on exogenous EPO administration. I confirm having declared any potential conflict of interest for all authors listed on this abstract No Disclosure of Interest None declared
Intraoperative Epidural Pressure in Patients with Positive Vs. Negative Sedimentation Sign Undergoing Spinal Surgery
Authors: Melloh M. , Barz T. , Staub L. , Lange J. , Merk H. R. , Follak N.
Published: June 2012

Introduction

The nerve root Sedimentation Sign (SedSign) in transverse magnetic resonance imaging (MRI) has been shown to discriminate well between selected patients with and without lumbar spinal stenosis (LSS). Previously it was demonstrated that a positive SedSign appears to identify patients who are less likely to benefit from nonsurgical treatment. It is still unknown which potential mechanisms may be responsible for the absence of nerve root sedimentation in transverse MRI scans in cases of severe LSS. Aim of our study was to identify the pressure values causing a positive SedSign in patients undergoing spinal surgery for LSS.

Materials and Methods

We measured the intraoperative epidural pressure in five patients with LSS and a positive SedSign and in five patients without LSS and a negative SedSign. Epidural pressure was measured using a Codman catheter in prone position under radioscopy at different locations in the lumbar spinal canal. Results: Patients with a negative SedSign had a mean epidural pressure of 9 mm Hg (minimum 8, maximum 11 mm Hg) independent of the location of the measurement. Breath and pulse-synchronous waves accounted for 1 to 3 mm Hg. In patients with mono-segmental LSS and a positive SedSign, the epidural pressure above and below the stenosis was similar (8 and 9 mm Hg respectively; minimum 7, maximum 12 mm Hg). At the level of the stenosis, the mean epidural pressure was 23 mm Hg (minimum 21, maximum 26 mm Hg). Whereas cranial of the stenosis breath and pulse-synchronous wave could be demonstrated, this wave was absent below the stenosis. There was no significant correlation between the diameter of the spinal canal and the level of the stenosis.

Conclusion

We conclude that in patients with LSS as a consequence of the increased epidural pressure (1) lumbar nerve roots are tethered at the level of the stenosis inhibiting the sedimentation of these nerve roots to the dorsal part of the dural sac in supine position, and (2) no breath and pulse-synchronous wave below the stenosis can be detected. However, these findings need confirmation in larger patient samples. Future research is warranted investigating the correlation between an increased epidural pressure and the level of lumbar stenosis. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared Barz T, Melloh M, Staub LP, et al. Nerve root sedimentation sign-evaluation of a new radiological sign in lumbar spinal stenosis. Spine 2010;;35(8):892–897.
Chemical Exchange Saturation Transfer and T2 Mapping in Subjects with Intervertebral Disk Degeneration
Authors: Kim M. , Chan Q. , Anthony M. P. , Samartzis D. , Cheung K. , Khong P.
Published: June 2012

Introduction

Intervertebral disk degeneration (IVD) on magnetic resonance imaging (MRI) is an etiological factor associated with low back pain. The (IVD) has been well acknowledged to degenerate as characterized by biochemical and morphological changes. T2 relaxation time has been suggested to be sensitive to changes in collagen and water content in cartilage and in the IVD. In the disk, the investigators have quantified chemical exchange saturation transfer (CEST) and its specificity as well as its correlation capacity for glycosaminoglycan (GAG) content (gagCEST). However, the correlation between conventional qualitative MRI assessment (T2-weighted) and quantitative MRI measurement, such as T2 and CEST, remains unknown. In this study, we aimed to investigate the association between CEST, T2 and degenerative grades in IVD using T2-weighted MRI in human subjects.

Materials and Methods

Total 21 subjects (8 females, 13 males; median age 34; age range: 24 to 58 years) with no prior spine surgery were recruited. Sagittal T2-weighted, CEST, and T2 MRI of the lumbar spine were obtained. All images of the lumbar spine were acquired using a 3T Achieva scanner. High-resolution T2-weighted disks were qualitatively graded according to Schneiderman's classification (score range: 0 to 3). CEST and T2 maps were quantitatively assessed based on a voxel-by-voxel basis.

Results

A decreasing trend of CEST and T2 values with increasing grade of degeneration was noted. The mean CEST values in L3/4, L4/5 and L5/S1 discs with Schneiderman grades 0 ( n = 41), 1 ( n = 10), 2 ( n = 7) and 3 ( n = 5) were 7.17 ± 1.10%, 6.00 ± 0.83%, 2.85 ± 0.39%, and 1.84 ± 0.27%, respectively. The mean T2 values in discs with Schneiderman grades 0 ( n = 41), 1 ( n = 10), 2 ( n = 7) and 3 ( n = 5) were 109.74 ± 12.40 ms, 83.84 ± 6.19 ms, 71.70 ± 3.44 ms, and 65.16 ± 2.97 ms, respectively. Schneiderman grade was correlated with both CEST (r = -0.67, p < 0.001) and T2 (r = -0.71, p)

Conclusion

Our results showed that CEST and T2 decreases with increasing grade of disk degeneration and that CEST values significantly correlated with T2. Our findings propose useful quantitative imaging tools with discriminatory capacity to assess early and end-stage IVD degeneration. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared