Stages Of Degenerative Disc Disease Research Articles

Roles of Chemokines in Intervertebral Disk Degeneration.

Intervertebral disc degeneration is the primary etiology of low back pain and radicular pain. This review examines the roles of crucial chemokines in different stages of degenerative disc disease, along with interventions targeting chemokine function to mitigate disc degeneration. The release of chemokines from degenerated discs facilitates the infiltration and activation of immune cells, thereby intensifying the inflammatory cascade response. The migration of immune cells into the venous lumen is concomitant with the emergence of microvascular tissue and nerve fibers. Furthermore, the presence of neurogenic factors secreted by disc cells and immune cells stimulates the activation of pain-related cation channels in the dorsal root ganglion, potentially exacerbating discogenic and neurogenic pain and intensifying the degenerative cascade response mediated by chemokines. Gaining a deeper comprehension of the functions of chemokines and immune cells in these processes involving catabolism, angiogenesis, and injury detection could offer novel therapeutic avenues for managing symptomatic disc disease.

Mobilisation efficacy in young patients with different stages of degenerative disc disease.

Lumbar vertebrae carry the greatest load from the spinal column, often leading to several pathologies, including degenerative disc disease (DDD), potentially disturbing spinal movement patterns. Mobilisation increases hypomobile segment mobility, however there is little evidence on mobilisation in patients suffering from different types of DDD. To assess the efficacy of mobilisation in young patients with DDD, as diagnosed by MRI. Thirty patients (24-35 years) participated in this study, and were divided into two groups, based on progression levels of DDD diagnosed by MRI (protrusion-PRO/extrusion-EXT). Twenty sessions of sustained stretch mobilisation (grade III) were applied to both groups over four weeks. Numeric Rating Scale (NRS), Oswestry Disability Index (ODI), straight leg raise (SLR), passive lumbar extension (PLE) and lumbar range of motion (ROM) assessed outcome variables. Three trial stages were investigated: pre-therapy (1), post-therapy (2) and follow-up (3). Age (p= 0.007) and NRS (p= 0.002) were significantly different before therapy. Patient outcomes were significantly improved for all parameters in both groups, except SLR which improved in the EXT group only (p= 0.043). Applied treatments improved patient outcomes and were statistically significant in both groups, however, better outcomes were observed in the EXT group during follow-up. Mobilisation was a safe and effective procedure for the treatment of DDD.

Quantitative evaluation of lumbar intervertebral disc degeneration by axial T2* mapping.

To quantitatively evaluate the clinical value and demonstrate the potential benefits of biochemical axial T2∗ mapping-based grading of early stages of degenerative disc disease (DDD) using 3.0-T magnetic resonance imaging (MRI) in a clinical setting.Fifty patients with low back pain and 20 healthy volunteers (control) underwent standard MRI protocols including axial T2∗ mapping. All the intervertebral discs (IVDs) were classified morphologically. Lumbar IVDs were graded using Pfirrmann score (I to IV). The T2∗ values of the anterior annulus fibrosus (AF), posterior AF, and nucleus pulposus (NP) of each lumbar IVD were measured. The differences between groups were analyzed regarding specific T2∗ pattern at different regions of interest.The T2∗ values of the NP and posterior AF in the patient group were significantly lower than those in the control group (P < .01). The T2∗ value of the anterior AF was not significantly different between the patients and the controls (P > .05). The mean T2∗values of the lumbar IVD in the patient group were significantly lower, especially the posterior AF, followed by the NP, and finally, the anterior AF. In the anterior AF, comparison of grade I with grade III and grade I with grade IV showed statistically significant differences (P = .07 and P = .08, respectively). Similarly, in the NP, comparison of grade I with grade III, grade I with grade IV, grade II with grade III, and grade II with grade IV showed statistically significant differences (P < .001). In the posterior AF, comparison of grade II with grade IV showed a statistically significant difference (P = .032). T2∗ values decreased linearly with increasing degeneration based on the Pfirrmann scoring system (ρ < −0.5, P < .001).Changes in the T2∗ value can signify early degenerative IVD diseases. Hence, T2∗ mapping can be used as a diagnostic tool for quantitative assessment of IVD degeneration.

Finite element simulation and clinical follow-up of lumbar spine biomechanics with dynamic fixations.

Arthrodesis is a recommended treatment in advanced stages of degenerative disc disease. Despite dynamic fixations were designed to prevent abnormal motions with better physiological load transmission, improving lumbar pain and reducing stress on adjacent segments, contradictory results have been obtained. This study was designed to compare differences in the biomechanical behaviour between the healthy lumbar spine and the spine with DYNESYS and DIAM fixation, respectively, at L4-L5 level. Behaviour under flexion, extension, lateral bending and axial rotation are compared using healthy lumbar spine as reference. Three 3D finite element models of lumbar spine (healthy, DYNESYS and DIAM implemented, respectively) were developed, together a clinical follow-up of 58 patients operated on for degenerative disc disease. DYNESYS produced higher variations of motion with a maximum value for lateral bending, decreasing intradiscal pressure and facet joint forces at instrumented level, whereas screw insertion zones concentrated stress. DIAM increased movement during flexion, decreased it in another three movements, and produced stress concentration at the apophyses at instrumented level. Dynamic systems, used as single systems without vertebral fusion, could be a good alternative to degenerative disc disease for grade II and grade III of Pfirrmann.

MRI-Based Classification of the Morphology and Pathology of the Annulus Fibrosus of the Intervertebral Disc

Introduction The high rate of recurrent disc herniation after discectomy is a prevalent problem. An effective biological annular repair could improve the surgical outcome in patients with contained disc herniation but otherwise minor degenerative changes. To estimate the integrity of the annulus fibrosus (AF) and judge different repair options a better understanding of disc morphology and pathology is crucial.1 Axial- and sagittal T2*-mapping are effective to detect early stages of degenerative disc disease and are especially suited to evaluate the interface between the proton-rich nucleus pulposus and the fibers of the annulus fibrosus.2,3 So far there is no classification of AF morphology or pathology as current classifications only describe localization and extend of the hernia itself. Materials and Methods Prospective consecutive case study of 100 patients requiring MRI diagnostic for suspected lumbar disc herniation. Beside the clinical standard MRI protocol with sagittal T1- and T2-weighted images, axial and sagittal T2*-mapping sequences of the affected and adjacent discs were performed using 3T MRI. Three observers used established classification schemes to assess the grade of degeneration (Pfirrmann, Benneker, Watanabe) and herniation (Carragee, Rajaserakan) and also developed a new classification protocol specific for the annulus fibrosus. Results In the preliminary data four types of annulus morphology/pathology could be found: type 1: healthy, uniform thickness of AF, clear demarcation between nucleus pulposus (NP) and AF. Type 2: concentric thinning with bulge, concentric tears, demarcation between NP and AF unclear. Type 3: nonconcentric thinning, ±radial fissures, ±protrusion, and type 4: herniations with further subgroups. Conclusion Based on preliminary axial and sagittal T2* images a new classification system for AF morphology and pathology could be established. Inter- and intraobserver liability is high. Disclosure of Interest None declared References Guterl CC, See EY, Blanquer SB, et al. Challenges and strategies in the repair of ruptured annulus fibrosus. Eur Cell Mater 2013;25:1–21 Stelzeneder D, Welsch GH, Kovács BK, et al. Quantitative T2 evaluation at 3.0T compared to morphological grading of the lumbar intervertebral disc: a standardized evaluation approach in patients with low back pain. Eur J Radiol 2012;81(2):324–330 Hoppe S, Quirbach S, Mamisch TC, Krause FG, Werlen S, Benneker LM. Axial T2 mapping in intervertebral discs: a new technique for assessment of intervertebral disc degeneration. Eur Radiol 2012;22(9):2013–2019

Histological and Immunohistochemical Protocol to Study Different Degrees of Severity of Lumbar Degenerative Discopathy

Introduction Literature on histological and immunohistochemical protocols that relate degenerative discopathy and its degree of wear is scarce. The purpose of this study was to analyze the structural degeneration of the intervertebral disc of patients with different degrees of degeneration, through histopathology, immunohistochemical, and cellular proliferation and apoptosis studies. Materials and Methods The intervertebral disc was obtained from patients with lumbar disc degenerative disease refractory to conservative treatment who required surgical treatment. The material was sent for histological study with hematoxylin and eosin stain (H&amp;E), Alcian/PAS, Masson trichrome, and safranin O/FCF, and immunohistochemistry through expression of the proteins to mark cell proliferation, Ki-67, and apoptosis, p53. MRI defined the degree of disc degeneration according to Pfirmann classification, and it was correlated with the evaluations of the different histological stains, and the positivity of the immunohistochemical markers. The present study was authorized by the ethics committee under number 0513. Results H&amp;E was effective to evaluate fissures of the fibrous ring, necrosis, and inflammation. Alcian/PAS stain allowed a better visualization of the chondrocyte clusters and of the acid mucopolysaccharide deposits in 86.7% of the samples. Masson trichrome identified the misalignment of collagen fibers in 93.4% of the samples, with greater definition. The safranin technique was considered the most sensitive and efficient stain to study the number and diameter of chondrocyte clusters. Immunohistochemistry showed 73% of positive expression of Ki-67 and p53, which are related, respectively, to the cell proliferation followed by cellular apoptosis. Conclusion The protocol enabled a better histological and molecular characterization of the degenerative disc according to different stages of degenerative disc disease. Disclosure of Interest A. Falavigna: Conflict with CNPq, FAPERGS, and AOSpine Latin America M. Peletti-Figueiró: None declared I. S. Aguiar: None declared M. Roesch-Ely: None declared D. C. Machado: None declared J. A. P. Henriques: None declared O. Righesso: None declared

Evaluation of a novel poly N-acetyl glucosamine (pGlcNAc) hydrogel for treatment of the degenerating intervertebral disc

AimsThe early stages of degenerative disc disease (DDD) primarily affect the disc nucleus pulposus (NP). Tissue-engineered strategies may enhance intervertebral disc (IVD) functionality. The aim of this study was to develop and evaluate a novel deacetylated poly-N-acetyl glucosamine (pGlcNAc) hydrogel characterizing its biochemical effect on human IVD cells as well as material biomechanical properties. Main methodsA novel deacetylated derivative of a marine diatom-derived glycosaminoglycan was developed into a hydrogel formulation as a potential therapy to treat degenerating IVD NP. In vitro biochemical studies were conducted using primary human disc cell cultures to evaluate cell viability, metabolic activity, proteoglycan and extracellular matrix protein expression. The biomechanical hydration kinetics and viscoelastic behavior of the hydrogel were determined and compared with the behavior of human lumbar NP. Key findingsDisc cell viability, metabolic activity, and proteoglycan content of the treated cells were observed to be significantly greater in experimental samples when compared to untreated control groups. RT-PCR and immunohistochemical data corroborated the expression of characteristic NP disc markers, aggrecan and type II collagen in cultured cells. Rheological data demonstrated that the elastic component of the hydrogel dominated the viscous component over a frequency range of 0.1 to 15.85rad/s. Of several formulations evaluated, a sulphated, deactylated derivative of the nanofiber derived pGlcNAc hydrogel demonstrated the most robust biologic effects on cell viability, metabolic activity, and proteoglycan expression. SignificanceThis in vitro study using human disc cells demonstrates that a sulphated deacetylated glycosaminoglycan derivative hydrogel possesses promising characteristics motivating further evaluation as a potential therapy for NP degeneration.

Axial T2* mapping in intervertebral discs: a new technique for assessment of intervertebral disc degeneration

To demonstrate the potential benefits of biochemical axial T2 mapping of intervertebral discs (IVDs) regarding the detection and grading of early stages of degenerative disc disease using 1.5-Tesla magnetic resonance imaging (MRI) in a clinical setting. Ninety-three patients suffering from lumbar spine problems were examined using standard MRI protocols including an axial T2 mapping protocol. All discs were classified morphologically and grouped as "healthy" or "abnormal". Differences between groups were analysed regarding to the specific T2 pattern at different regions of interest (ROIs). Healthy intervertebral discs revealed a distinct cross-sectional T2 value profile: T2 values were significantly lower in the annulus fibrosus compared with the nucleus pulposus (P = 0.01). In abnormal IVDs, T2 values were significantly lower, especially towards the centre of the disc representing the expected decreased water content of the nucleus (P = 0.01). In herniated discs, ROIs within the nucleus pulposus and ROIs covering the annulus fibrosus showed decreased T2 values. Axial T2 mapping is effective to detect early stages of degenerative disc disease. There is a potential benefit of axial T2 mapping as a diagnostic tool, allowing the quantitative assessment of intervertebral disc degeneration.

Interdependence Between Disc Space Height, Range of Motion and Clinical Outcome in Total Lumbar Disc Replacement

Clinical and radiologic assessment obtained from an ongoing prospective trial following total lumbar disc replacement (TDR) with ProDisc II. To analyze the interaction between the parameters of disc space height (DSH), range of motion (ROM) and clinical outcome scores following TDR. The interdependence between DSH, ROM and the clinical symptomatology has been well documented for patients with degenerative disc disease, fusion candidates and healthy control subjects. In the case of TDR, previously published data show conflicting results. All TDRs were performed monosegmentally at L4/5 or L5-S1. The clinical outcome assessment included the patient's subjective outcome evaluation, Visual Analogue Scale, and Oswestry Disability Index scores (ODI). The radiologic evaluation included measurement of the mean, anterior and posterior DSH, as well as the ROM. The parameters were correlated pre- and postoperatively with each other. Data from 62 patients with an average follow-up of 42.4 months (range: 24.2-77.6 months) were included in this study. Visual Analogue Scale and ODI scores showed a significant and maintained improvement in comparison to preoperative levels (P < 0.0001). The DSH increased from 5.7 mm (range: 2-11.3 mm) to 11.2 mm (range: 8-13.4 mm), whereas ROM decreased from 8.1 degrees (range: 0 degrees-23.1 degrees) to 5.1 degrees (range: 0 degrees-12.8 degrees). This loss in ROM was significant following TDR at L5-S1 (P < 0.01). Preoperative DSH and ROM were positively correlated with postoperative segmental ROM (r = 0.45, P < 0.002 and r = 0.35, P < 0.01). The highest satisfaction rates were observed in the group of patients with the smallest preoperative DSH of < 4.5 mm (P < 0.024). A significant interdependence was observed between the parameters DSH, ROM and the clinical outcome following TDR. Whilst the DSH is restored, TDR leads to a significant decrease in postoperative ROM, particularly at the lumbosacral junction. Higher preoperative DSH and ROM revealed a beneficial effect on the postoperative segmental mobility. The subjective outcome evaluation indicates that TDR is a viable treatment option even in advanced stages of degenerative disc disease in the absence of other contraindications, in particular facet joint arthropathies.

Computer analysis of spinal segment motion in degenerative disc disease with and without axial loading.

The center of rotation of the spinal motion segment is an indicator of spinal instability. However, the motion segment does not move about a single fixed axis of rotation, but rather a locus of instantaneous axes of rotation, the centrode. This paper studies centrodes in various stages of degenerative disc disease comparing them with normal spines. Computer analysis is undertaken in 47 cadaveric spines, 22 of which also were evaluated with axial loading. The normal centrode fell within the posterior half of the disc space and averaged 21 mm in ten specimens. In the earliest stages of degenerative disc disease, the centrode lengths increased significantly (average 116 mm). Specimens with moderate disc degeneration also migrated inferiorly into the L5 vertebra. Axial loading did not appear to influence the centrode lengths or position. This technique is highly sensitive, detecting 94% of the abnormal spines as compared with only 25% detected by means of measuring an excessive range of motion on flexion and extension radiographs. This method provides a highly reliable and quantifiable method of detecting early changes in spinal motion in degenerative disc disease prior to the well recognized radiographic abnormalities.