Intervertebral Discs Of Patients Research Articles

Different Load-Induced Alterations in Intervertebral Discs Between Low Back Pain Patients and Controls: A T2-map Study.

Prospective cohort study. Investigate load-induced effects in lumbar intervertebral discs (IVDs) and differences between low back pain (LBP) patients and controls. T2-map values, obtained from quantitative MRI sequences, reflect IVD tissue composition and integrity. Feasibility studies with T2-mapping indicate different load-induced effects in entire IVDs and posterior IVD parts between LBP patients and controls. Larger studies are required to confirm these findings and increase the understanding of specific characteristics distinguishing IVD changes in LBP patients compared with controls. Lumbar IVDs of 178 patients (mean age: 43.8yr; range: 20-60yr) with >3 months of LBP and 74 controls (mean age: 40.3yr; range: 20-60yr) were imaged with T2-map sequence in a 3T scanner in supine position without axial load, immediately followed by a repeated examination, using the same sequence, with axial load. On both examinations, mean T2-map values were obtained from entire IVDs and from central/posterior IVD parts on the three midsagittal slices in 855 patient IVDs and 366 control IVDs. Load-induced effect was compared with Fold-change ratio and adjusted for IVD-degeneration grade. Loading induced an increase in T2-map values in both patients and controls. Excluding most extreme values, the ranges varied between -15% and +35% in patients and -11% and +36% in controls (first to 99th percentile). Compared with controls, the T2-map value increase in patients was 2% smaller in entire IVDs (Fold-change: 0.98, P=0.031), and for central and posterior IVD parts 3% (Fold-change: 0.98, P=0.005), respectively, 2% (Fold-change: 0.9, P=0.015) smaller. This quantitative study confirmed diverse load-induced behaviors between LBP patients and controls, suggesting deviant biomechanical characteristics between IVDs in patients and controls not only attributed to the global grade of degeneration. These findings are an important step in the continuous work of identifying specific IVD phenotypes for LBP patients. Level II.

Intradiscal administration of autologous platelet-rich plasma in patients with Modic type 1 associated low back pain: A prospective pilot study.

Various treatments for chronic low back pain (LBP) have been reported; among them, platelet-rich plasma (PRP) as a regenerative medicine has attracted much attention. Although Modic type 1 change (MC1) is associated with LBP, no treatment has been established so far. In addition, no studies have administered PRP to intervertebral discs (IVDs) in patients with LBP, targeting MC1 only. Thus, the purpose of this study was to determine the safety and efficacy of PRP administration to the IVDs in patients with MC1 experiencing LBP. PRP was injected intradiscally to 10 patients with MC1 experiencing LBP. Patients were followed prospectively for up to 24 weeks after primary administration. Physical condition, laboratory data, and lumbar x-ray images were evaluated for safety assessment. Furthermore, to evaluate the effectiveness of PRP, patient-reported outcomes were considered. In addition, changes in MC1 were assessed using magnetic resonance imaging (MRI). There were no adverse events in the laboratory data or lumbar X-ray images after administration. The mean visual analog scale, which was 70.0 ± 13.3 before the treatment, significantly decreased 1 week after PRP administration and was 39.0 ± 28.8 at the last observation. Oswestry disability index and Roland Morris disability questionnaire scores promptly improved after treatment, and both improved significantly 24 weeks after PRP administration. Follow-up MRI 24 weeks after treatment showed a significant decrease in the mean high-signal intensity of fat-suppressed T2-weighted imaging from 10.1 to 7.90 mm2 compared with that before PRP administration. The safety and efficacy of PRP administration to the IVDs of patients with MC1 experiencing LBP were identified. Post-treatment MRI suggested improvement in inflammation, speculating that PRP suppressed inflammation and consequently relieved the patient's symptoms. Despite the small number of patients, this treatment is promising for patients with MC1 experiencing LBP. The study protocol has been reviewed and approved by the Certified Committee for Regenerative Medicine and the Japanese Ministry of Health, Labor and Welfare (Japan Registry of Clinical Trials [jRCT] No. jRCTb042210159).

Digoxin protects against intervertebral disc degeneration via TNF/NF-κB and LRP4 signaling.

Intervertebral disc degeneration (IVDD) is a leading cause of low back pain (LBP). The pathological process of IVDD is associated with inflammatory reactions and extracellular matrix (ECM) disorders. Digoxin is widely used for treating heart failure, and it has been reported to have anti-inflammatory effects. This study is to investigate the role of digoxin in the pathogenesis of intervertebral disc degeneration as well as the involved molecular mechanism, particularly the potential target protein. We exploited a rat needle model to investigate digoxin's role in intervertebral disc degeneration in vivo. Safranin O staining was used to measure cartilaginous tissue in the intervertebral disc. The morphological changes of intervertebral discs in animal models were determined by Hematoxylin-Eosin (H&E) staining and the pathological score. Primary nucleus pulposus cells (NP cells) from intervertebral discs of patients and murine were used in the present study. Western-Blotting assay, Real-time PCR assay, immunofluorescence staining, and immunochemistry were used to detect the role of digoxin in anti-TNF-α-induced inflammatory effects in vitro. Transfection of siRNA was used to regulate low-density lipoprotein receptor-related protein 4 (LRP4) expression in NP cells to investigate the potential protein target of digoxin. Digoxin protected against intervertebral disc degeneration in rat needle models. Digoxin was found to exert its disc-protective effects through at least three different pathways by a) suppressing TNF-α-induced inflammation, b) attenuating ECM destruction, c) significantly promoting ECM anabolism. Additionally, LRP4 was found to be the downstream molecule of digoxin in NP cells for anti-inflammation and regulation of ECM metabolism. The knockdown of LRP4 downregulated the protective effect of digoxin in NP cells. These findings suggest that digoxin may be a potential therapeutic agent for intervertebral disc degeneration through anti-catabolism and pro-anabolism. Digoxin might also work as an alternative for other inflammation-related diseases.

Morphological alterations of lumbar intervertebral discs in patients with adolescent idiopathic scoliosis

BACKGROUND CONTEXTEtiology of adolescent idiopathic scoliosis (AIS) is still unknown. Prior in vitro research suggests intervertebral disc pathomorphology as a cause for the initiation and progression of the spinal deformity, however, this has not been well characterized in vivo. PURPOSETo quantify and compare lumbar disc health and morphology in AIS to controls. STUDY DESIGN/SETTINGCross-sectional study. METHODSAll lumbar discs were imaged using a 3T MRI scanner. T2-weighted and quantitative T2* maps were acquired. Axial slices of each disc were reconstructed, and customized scripts were used to extract outcome measurements: Nucleus pulposus (NP) signal intensity and location, disc signal volume, transition zone slope, and asymmetry index. Pearson's correlation analysis was performed between the NP location and disc wedge angle for AIS patients. ANOVAs were utilized to elucidate differences in disc health and morphology metrics between AIS patients and healthy controls. α=0.05. RESULTSThere were no significant differences in disc health metrics between controls and scoliotic discs. There was a significant shift in the NP location towards the convex side of the disc in AIS patients compared to healthy controls, with an associated increase of the transition zone slope on the convex side. Additionally, with increasing disc wedge angle, the NP center migrated towards the convex side of the disc. CONCLUSIONSThe present study elucidates morphological distinctions of intervertebral discs between healthy adolescents and those diagnosed with AIS. Discs in patients diagnosed with AIS are asymmetric, with the NP shifted towards the convex side, which was exacerbated by an increased disc wedge angle. CLINICAL SIGNIFICANCEInvestigation of the MRI signal distribution (T2w and T2* maps) within the disc suggests an asymmetric pressure gradient shifting the NP laterally towards the convexity. Quantifying the progression of these morphological alterations during maturation and in response to treatment will provide further insight into the mechanisms of curve progression and correction, respectively.

A common variant rs2054564 in ADAMTS17 is associated with susceptibility to lumbar spondylosis

The molecular pathophysiology underlying lumbar spondylosis development remains unclear. To identify genetic factors associated with lumbar spondylosis, we conducted a genome-wide association study using 83 severe lumbar spondylosis cases and 182 healthy controls and identified 65 candidate disease-associated single nucleotide polymorphisms (SNPs). Replication analysis in 510 case and 911 control subjects from five independent Japanese cohorts identified rs2054564, located in intron 7 of ADAMTS17, as a disease-associated SNP with a genome-wide significance threshold (P = 1.17 × 10–11, odds ratio = 1.92). This association was significant even after adjustment of age, sex, and body mass index (P = 7.52 × 10–11). A replication study in a Korean cohort, including 123 case and 319 control subjects, also verified the significant association of this SNP with severe lumbar spondylosis. Immunohistochemistry revealed that fibrillin-1 (FBN1) and ADAMTS17 were co-expressed in the annulus fibrosus of intervertebral discs (IVDs). ADAMTS17 overexpression in MG63 cells promoted extracellular microfibrils biogenesis, suggesting the potential role of ADAMTS17 in IVD function through interaction with fibrillin fibers. Finally, we provided evidence of FBN1 involvement in IVD function by showing that lumbar IVDs in patients with Marfan syndrome, caused by heterozygous FBN1 gene mutation, were significantly more degenerated. We identified a common SNP variant, located in ADAMTS17, associated with susceptibility to lumbar spondylosis and demonstrated the potential role of the ADAMTS17-fibrillin network in IVDs in lumbar spondylosis development.

CILP-2 Expression in the Intervertebral Discs of Patients with Radiculopathy

CILP-2 Expression in the Intervertebral Discs of Patients with Radiculopathy

Analysis of the Biomechanical Behavior of the Intervertebral Discs by Modeling Three-Phase Finite Elements

Intervertebral discs act as a shock absorber to counteract the blows to the spine. These elements have the ability to deform when applied pressure, thus reducing the intensity of impacts. The main shape of discs is spherical when not under pressure; but when they are placed between the vertebrae, they expand under the pressure. One of the important functions of intervertebral discs is to facilitate movements in the spine In order to study biological mechanics as one of the engineering infrastructures, in this paper, the combined modeling of finite element intervertebral discs as a saturated porous soft tissue is discussed. First, according to the continuum mechanics, the mathematical model is extracted and then the finite element model is prepared by ANSYS program package. Based on the different loads according to the available medical information, the biomechanical behavior of the disk was investigated. This model can be used to investigate the behavior of intervertebral discs in patients before or after surgery. In this paper, in addition to the mathematical model, the mechanical behavior of the disk and the stress distribution under different loads were investigated.

The Appropriateness Criteria of Abdominal Fat Measurement at the Level of the L1-L2 Intervertebral Disc in Patients With Obesity.

BackgroundIn this study, we proposed to use MR images at L1-L2 (lumbar) intervertebral disc level to measure abdominal fat area in patients with obesity. The quantitative results would provide evidence for the individualized assessment of the severity of obesity.MethodsAll patients in the IRB-approved database of Beijing Friendship Hospital who underwent bariatric surgery between November 2017 and November 2019 were recruited. We retrospectively reviewed upper abdominal magnetic resonance (MR) data before surgery. We analyzed the correlation and consistency of the area of abdominal subcutaneous adipose tissue (ASAT) and visceral adipose tissue (VAT) measured at the L1-L2 and L2-L3 levels on MR images. We randomly distributed the cases into prediction model training data and testing data at a ratio of 7:3.ResultsTwo hundred and forty-five subjects were included. The ASAT and VAT results within the L1-L2 and L2-L3 levels were very similar and highly correlated (maleASAT: r=0.98, femaleASAT: r=0.93; maleVAT: r=0.91, femaleVAT: r=0.88). There was no substantial systematic deviation among the results at the two levels, except for the ASAT results in males. The intraclass correlation coefficients (ICCs) were 0.91 and 0.93 for maleASAT and femaleASAT, and 0.88 and 0.87 for maleVAT and femaleVAT, respectively. The ASAT/VAT area at the L2-L3 level was well predicted. The coefficient β of linear regression that predicted L2-L3 ASAT from L1-L2 ASAT was 1.11 for males and 0.99 for females. The R-squares were 0.97 and 0.91, respectively. For VAT prediction, the coefficient β was 1.02 for males and 0.96 for females. The R-squares were 0.82 and 0.77, respectively.ConclusionFor patients with obesity, the L1-L2 intervertebral disc level can be used as the substitution of L2-L3 level in abdominal fat measurement.

Viable Disc Tissue Allograft Supplementation; One- and Two-level Treatment of Degenerated Intervertebral Discs in Patients with Chronic Discogenic Low Back Pain: One Year Results of the VAST Randomized Controlled Trial

Background: A viable disc tissue allograft has been developed to supplement tissue loss associated with degenerative lumbar disc disease and the development of chronic discogenic lower back pain. Objectives: Viable disc allograft was injected into painful degenerated discs to evaluate safety and determine whether it can improve pain and function. Study Design: Patients received an active treatment of allograft or saline, or continued with nonsurgical management (NSM). Prior to entering the study, patients had back pain for a minimum of 6 months before treatment that was recalcitrant to nonoperative treatment modalities. Standardized outcome measures were used to evaluate the patient’s condition before and after treatment. Primary endpoints included improvement in Oswestry Disability Index (ODI) and Visual Analog Scale of Pain Intensity (VASPI). Conventional radiographs and magnetic resonance imaging scans were used to assess disc space height and spinal alignment, and to determine the degree of disc degeneration. Patients were followed for one year after enrollment. The NSM group could cross over to the allograft group after 3 months. Setting: This multicenter trial was completed in outpatient surgical centers and office injection suites. A total of 218 patients with chronic low back pain secondary to single-level or 2-level degenerative disc disease were enrolled. Inclusion criteria included pretreatment VASPI >= 40 mm, ODI score >= 40 and symptoms present longer than 6 months. Patients were blinded and randomized to receive intradiscal injections of either viable disc allograft or saline. Patients randomized to the NSM group continued existing treatment. Patients were assessed at 6 and 12 months. Adverse events (AEs) were continually assessed. Methods: The VAST trial is a prospective, multicenter, blind, randomized clinical trial (RCT) for patients with single-level or 2-level degenerative lumbar disc disease. Results: At 12 months, clinically meaningful improvements in mean VASPI and ODI scores were achieved in the investigational allograft and saline groups. A responder analysis demonstrated a clinically meaningful reduction in ODI of >= 15 points at 12 months that was statistically significant; 76.5% of patients randomized to allograft were responders (P = 0.03) compared to 56.7% in the saline group. A responder group characterized by a ? 20 point reduction in pain at 12 months achieved a statistically significant reduction in pain compared to the saline group (P = 0.022). In the allograft group, 11 safety adverse events occurred in 141 patients (3.5%) and there were no persistently symptomatic AEs. Limitations: Limitations of this study include a comparison to saline that has been shown to be more representative of an active comparator as opposed to a placebo. In addition, 36 patients were lost to follow-up; this loss resulted in the saline and NSM/crossover groups being smaller than the predetermined group size to have an appropriately powered analysis. Conclusions: This large, prospective blinded RCT demonstrated safety and efficacy results indicating that viable disc tissue allograft may be a beneficial nonsurgical treatment for patients who have chronically painful lumbar degenerative discs. Further studies would be optimal to confirm efficacy Key words: Viable disc tissue allograft, discogenic back pain, allograft supplementation, degenerative disc disease, low back pain, intervertebral disc, intradiscal injection

Toll-like receptor 2 induced senescence in intervertebral disc cells of patients with back pain can be attenuated by o-vanillin

BackgroundThere is an increased level of senescent cells and toll-like teceptor-1, -2, -4, and -6 (TLR) expression in degenerating intervertebral discs (IVDs) from back pain patients. However, it is currently not known if the increase in expression of TLRs is related to the senescent cells or if it is a more general increase on all cells. It is also not known if TLR activation in IVD cells will induce cell senescence.MethodsCells from non-degenerate human IVD were obtained from spine donors and cells from degenerate IVDs came from patients undergoing surgery for low back pain. Gene expression of TLR-1,2,4,6, senescence and senescence-associated secretory phenotype (SASP) markers was evaluated by RT-qPCR in isolated cells. Matrix synthesis was verified with safranin-O staining and Dimethyl-Methylene Blue Assay (DMMB) confirmed proteoglycan content. Protein expression of p16INK4a, SASP factors, and TLR-2 was evaluated by immunocytochemistry (ICC) and/or by enzyme-linked immunosorbent assay (ELISA).ResultsAn increase in senescent cells was found following 48-h induction with a TLR-2/6 agonist in cells from both non-degenerate and degenerating human IVDs. Higher levels of SASP factors, TLR-2 gene expression, and protein expression were found following 48-h induction with TLR-2/6 agonist. Treatment with o-vanillin reduced the number of senescent cells, and increased matrix synthesis in IVD cells from back pain patients. Treatment with o-vanillin after induction with TLR-2/6 agonist reduced gene and protein expression of SASP factors and TLR-2. Co-localized staining of p16INK4a and TLR-2 demonstrated that senescent cells have a high TLR-2 expression.ConclusionsTaken together our data demonstrate that activation of TLR-2/6 induce senescence and increase TLR-2 and SASP expression in cells from non-degenerate IVDs of organ donors without degeneration and back pain and in cells from degenerating human IVD of patients with disc degeneration and back pain. The senescent cells showed high TLR-2 expression suggesting a link between TLR activation and cell senescence in human IVD cells. The reduction in senescence, SASP, and TLR-2 expression suggest o-vanillin as a potential disease-modifying drug for patients with disc degeneration and back pain.

Short-Term Effect of Lumbar Traction on Intervertebral Discs in Patients with Low Back Pain: Correlation between the T2 Value and ODI/VAS Score.

The effect of lumbar traction on low back pain (LBP) patients is controversial. Our study aims to assess changes in the intervertebral disc water content after lumbar traction using T2 mapping and explore the correlation between changes in the T2 value and Oswestry Disability Index (ODI)/visual analogue scale (VAS) score. Lumbar spine magnetic resonance imaging was performed, and the ODI/VAS scores were recorded in all 48 patients. Midsagittal T2-weighted imaging and T2 mapping were performed to determine the Pfirrmann grade and T2 value. Then, the T2 values were compared between pre- and posttraction, and the correlation between changes in the T2 value and ODI/VAS scores were examined. In the traction group, the changes in the nucleus pulposus (NP) T2 values for Pfirrmann grades II-IV and the annulus fibrosus (AF) T2 values for Pfirrmann grade II were statistically significant after traction (P < 0.05). Changes in the mean NP T2 value of 5 discs in each patient and in the ODI/VAS score showed a strong correlation (r = 0.822, r = 0.793). T2 mapping can be used to evaluate changes in the intervertebral disc water content. Ten sessions of traction resulted in a significant increase in quantitative T2 measurements of the NP in discs for Pfirrmann grade II-IV degeneration and remission of the patients' clinical symptoms in the following 6 months. Changes in the mean NP T2 value of 5 discs in each patient were strongly correlated with changes in the ODI/VAS score.

Characterization of microenvironmental changes in the intervertebral discs of patients with chronic low back pain using multiparametric MRI contrasts extracted from Z-spectrum

Z-spectral MRI data were analyzed to produce multiparametric metabolic and microenvironmental contrasts for identifying intervertebral discs with/without pain symptom and sore pain. Z-spectra data were collected from the lumbar discs of 26 patients with non-specific chronic low bck pain (CLBP) and 21 asymptomatic controls (AC) with a chemical exchange saturation transfer (CEST). Data were fitted to quantify the CEST effects from glycosaminoglycan, amide proton transfer (APT), nuclear Overhauser enhancement (NOE), semi-solid magnetization transfer contrast effects, and the direct saturation of water. Multiparametric maps were computed from the fitted peak amplitudes, and the average values were calculated from all five lumber discs. Those parameters were compared between the CLBP and AC groups and between the subgroups with and without (Nsore) sore pain. The discs in symptomatic patients have lower water content, collagen-bound water and collagen than the discs in AC (P < 0.05). Additionally, Z-sepctral MRI indicated that the discs in the sore subgroup had less water, collagen-bound water and collagen, and likely lower pH compared to the Nsore subgroup (P < 0.05). Lower pH as measured with reduced APT and NOE effects may be an important pathological factor causing sore pain of the back. Z-spectral MRI with its multiparametric metabolic and microenvironmental contrasts has been demonstrated to identify discs with and without pain symptom or sore pain, providing more important information of CLBP.

The adipokine profile and elevation of the RANKL/OPG ratio in vertebral bodies and intervertebral discs of patients with vertebral osteomyelitis: Implications for the disease pathogenesis

The adipokine profile and elevation of the RANKL/OPG ratio in vertebral bodies and intervertebral discs of patients with vertebral osteomyelitis: Implications for the disease pathogenesis

Evaluation of patients with cervical spine injury and predicting the risk and severity of acute spinal cord injury after a minor trauma

Introduction: The relevance of MR image parameters for predicting the risk and severity of acute SCI in patients after a minor trauma to the cervical spine has not yet been established. The aim of the present study was to investigate the spinal canal diameter and the space available for the cord at the level of the intervertebral disc in patients suffering from acute cervical SCI after a minor trauma to the cervical spine.Materials & Methods: On the magnetic resonance images the following parameters were recorded: sagittal diameter of the vertebral body, the sagittal outer diameter of the subarachnoid space at the midpoint of the vertebra, the sagittal outer diameter of the subarachnoid space at the level of the intervertebral disc, and the sagittal diameter of the spinal cord at the levels C2 and T1. Results: it was found that there were significant and positive correlations between investigated parameters (i.e., mid vertebral and disc-level canal diameters, TPR-MRI). No significant correlations between any of the parameters and height or weight were detected. Furthermore, there was no significant correlation between any of the parameters and the ASIA motor or sensory score.Conclusions: Assessment of the number of segments of the spinal cord involved, by MR Imaging is helpful in predicting the prognosis of the patient. Present study states that patient at risk of acute SCI after minor trauma can be identified by applying a disc level canal.

Comparative analysis of treatment results in patients with disс herniation of different age groups

Objective. To perform comparative analysis of the results of surgical treatment of patients with intervertebral disc herniation of different age groups. Material and Methods. The results of treatment of 2,448 patients (1,307 men and 1,141 women) with lumbar intervertebral disc herniation were analyzed. Out of them, 393 (16 %) people were elderly and senile patients with a mean age of 66 years. Evaluation of the treatment results in patients with herniated intervertebral discs was carried out in two groups: Group I – young and middle-aged patients; and Group II – elderly and senile patients. Mandatory preoperative evaluation included clinical and neurological examination, radiation diagnostic methods (X-ray, CT, CT-myelography, MRI), and survey using scales and questionnaires (VAS, ODI, CCI). Results. Body mass index (BMI), blood loss, duration of surgery, and length of hospital stay were statistically significantly greater in patients of Group II. In terms of pain, quality of life before and within 5 years after surgical treatment, patients of groups I and II have no statistically significant differences. The total complication rate was 4.9 %, while in patients of Group II complications developed statistically significantly more often (1.7 times) than in patients of Group I (p = 0.02). The most common complication was unintentional durotomy, which occurred in 3.6 % of cases, without statistically significant differences between groups. Epidural hematomas requiring revision intervention were observed in 13 patients, statistically significantly more often in patients of Group II (p = 0.04). The volume of blood loss in patients of Group II is significantly greater (p < 0.001). The cumulative index of reoperations over the 5-year follow-up period in Group I was 11.5 %, in Group II – 13.6 %. During the first year, reoperations in Group I amounted to 6.0 %, in Group II – 8.7 % (p = 0.05), which indicates the possible effect of age on the frequency of repeated operations. Convincing data on the effect of BMI and the comorbidity index on this indicator have not been obtained. The most common cause of reoperation in patients with herniated discs in both groups was hernia recurrence at the operated level, while the relapse rate in Group II was slightly higher – 46 % (n = 37) compared with 36 % (n = 168) in Group I. Conclusion. No difference was found between the clinical outcomes of surgical treatment of herniated intervertebral discs in patients of different age groups during a 5-year follow-up period. Elderly and senile age is a predictor of a higher frequency of early and intraoperative complications, an increase in the surgery duration and in the volume of intraoperative blood loss. Obesity and concomitant somatic pathology do not affect the clinical outcomes of surgical treatment and the cumulative index of repeated operations in patients with herniated discs of the lumbar spine.

Magnetic Resonance Imaging of Trunk Musculature and Intervertebral Discs in Patients with Spinal Cord Injury with Thoracolumbar Vertebral Fractures: A Prospective Study.

Study DesignThis study is a prospective clinical study.PurposeThis study aims to evaluate the characteristics of trunk musculature and intervertebral discs by using magnetic resonance imaging in patients with spinal cord injuries (SCIs) with thoracic and lumbar fractures. Overview of LiteratureMuscle atrophy is an immediate consequence of SCI and is associated with secondary complications. At present, there are limited clinical data on muscle and disc responses to fractures of the thoracic and lumbar spine.MethodsA total of 51 patients with a mean age of 31.75±10.42 years who suffered traumatic SCI were included in this study. Complete neurological examinations (American Spinal Injury Association grading) and magnetic resonance imaging (MRI) were performed at the time of admission and at 3–6 months after injury to study the neurological status and disc and trunk parameters. The type of management (operative or conservative) was decided on the basis of clinical, radiological, and MRI evaluations, and a robust rehabilitation program was initiated.ResultsDisc parameters including disc angle, skin angle, cross-sectional area (CSA), and disc height and trunk parameters (mean trunk width, mean trunk depth, and CSA of the lumbar muscles) decreased significantly (p <0.001) during the first 3 months after SCI. However, improvements were observed in disc and muscle parameters at the 6-month follow-up, but these parameters did not return to normal levels. Neither initial neurological status (complete vs. incomplete) nor type of management (operative vs. conservative) had a significant effect on these parameters.ConclusionsSpinal trauma leads to alterations in the morphology of the vertebral column, spinal cord, intervertebral discs, and paraspinal muscles in the initial phase of injury. The extent of these changes may determine the initial neurological deficit and subsequent recovery. Although this study did not identify any statistically significant effect of neurological status or management strategy on these parameters, rehabilitation was found to result in the improvement of these parameters in the later phase of recovery. Future studies are required to evaluate the exact causes of these alterations and the potential benefits of rehabilitation strategies and to minimize these changes.

Characterization of the microstructure of the intervertebral disc in patients with chronic low back pain by diffusion kurtosis imaging.

Multivariate analysis of T2-weighted signal, diffusion ADC, and DKI parameters and tractography were used to differentiate chronic non-specific low back pain (CLBP) patients and asymptomatic controls (AC). A total of 30 patients with CLBP and 23 AC underwent diffusion kurtosis imaging (DKI) of lumbar spine with a 3T MRI scanner to get the ADC values and seven parameters of DKI in the nucleus pulposus (NP) of the intervertebral disc. The tractography and the tract-related parameters as other parameters were also generated to indicate the intactness of annulus fibrosus (AF). T2-grades of the discs were also quantified based on an eight-grade degeneration grading system. ADC and T2-grades were compared with DKI parameters for the differentiation of CLBP and AC groups. There was no difference in the T2 grades, ADC value, and multiple parameters in DKI of NP between CLBP and AC groups (P > 0.05). The average FA values in NP in AC group were found significantly higher than in the CLBP group (P < 0.05). The scores for the intactness of AF of the intervertebral discs were significantly different in CLBP and AC groups, with 90% of sensitivity and 70% specificity (P < 0.05). Additionally, there were significantly differences in the length and volume values of the AF in CLBP and AC groups (P < 0.05). DKI is a good noninvasive method, and it might help to differentiate CLBP from AC. Particularly, the continuation of DKI tractography reflects the presence of annulus fibrosus fissures, an important character in the generation of the low back pain. These slides can be retrieved under Electronic Supplementary Material.

The Traceability of Mesenchymal Stromal Cells After Injection Into Degenerated Discs in Patients with Low Back Pain.

Low back pain is a major health issue and one main cause to this condition is believed to be intervertebral disc (IVD) degeneration. Stem cell therapy for degenerated discs using mesenchymal stromal cells (MSCs) has been suggested. The aim of the study was to investigate the presence and distribution pattern of autologous MSCs transplanted into degenerated IVDs in patients and explanted posttransplantation. IVD tissues from four patients (41, 45, 47, and 47 years of age) participating in a clinical feasibility study on MSC transplantation to degenerative discs were investigated. Three patients decided to undergo fusion surgery at time points 8 months and one patient at 28 months posttransplantation. Pretransplantation, MSCs from bone marrow aspirate were isolated by centrifugation in FICOLL® test tubes and cultured (passage 1). Before transplantation, MSCs were labeled with 1 mg/mL iron sucrose (Venofer®) and 1 × 106 MSCs were transplanted into degenerated IVDs. At the time point of surgery, IVD tissues were collected. IVD tissue samples were fixated, embedded in paraffin, and sections prepared. IVD samples were stained with Prussian Blue, by which iron deposits are visualized and examined (light microscopy). Immunohistochemistry (IHC), including SOX9 (sex determining region Y box 9), Coll2A1 (collagen 2A1), and cell viability (TUNEL) were performed. Cells positive for iron deposits were observed in IVD tissues (3/4 patients). The cells/iron deposits were observed in clusters and/or as solitary cells in regions in IVD tissue samples [regions of interest (ROIs)]. By IHC, SOX9- and Coll2A1-positive cells were detected in the same regions as the detected cells/iron deposits. A few nonviable cells were detected by TUNEL assay in ROIs. Results demonstrated that MSCs, labeled with iron sucrose, transplanted into degenerated IVDs were detectable 8 months posttransplantation. The detected cellular activity indicates that MSCs have differentiated into chondrocyte-like cells and that the injected MSCs and/or their progeny have survived since the cells were found in large cluster and as solitary cells which were distributed at different parts of the IVD.

MRI-biochemical follow up measurements of lumbar intervertebral disc in patients with leg length discrepancy: Is it possible to alter cartilage damage with conservative therapy?

ObjectiveEffect of conservative therapy on intervertebral discs (IVD) in patients with leg-length-discrepancy (LLD). M&MSeventy lumbar IVDs of 14 participants (five with LLD 10–20 mm) were examined using a 3T-MRI-scanner. Morphological (Pfirrmann) and molecular (glycosaminoglycan-chemical-exchange-saturation-transfer, gagCEST) grading was assessed before and after a four-month therapy (physiotherapy and shoe inlays). ResultsSignificantly lower GAG values in patients with LLD were found (L5/S1, p = 0.02). After therapy, a trend towards higher gagCEST values in patients with LLD was observed (2.48 ± 1.77% vs. 1.79 ± 0.79%; p > 0.05). ConclusionLLD represents a risk factor for molecular alterations of lumbar IVDs. Only minor effects of conservative therapy on these alterations could be found.

Assessment of glycosaminoglycan content in intervertebral discs of patients with leg length discrepancy: A pilot study

ObjectiveLeg length discrepancy (LLD) could be a predisposing factor for early degeneration of lumbar intervertebral discs (IVD). The purpose of this study was to elucidate the molecular effect of LLD on IVDs. MethodsIVDs of Eleven patients (25.6 ± 4.3years) with LLD (>10 mm) and 14 control subjects (23.9 ± 3.5years) were compared using a 3T-MR scanner. Morphological T2-weighted and glycosaminoglycan-chemical-exchange-saturation-transfer (gagCEST) sequences were performed. ResultsNo differences in morphological Pfirrmann grading were found (p > 0.05). In contrast, nucleus-pulposus-gagCEST-values of L5/S1 were significantly lower (p = 0.0008). ConclusionOur results suggest that LLD is a predisposing factor for molecular IVD alterations, which are detectable even before morphological pathologies could be found.