Genetic and Functional Studies of the Intervertebral Disc: A Novel Murine Intervertebral Disc Model

PubMed Central

Pelle, Dominic W.; Peacock, Jacqueline D.; Schmidt, Courtney L.; Kampfschulte, Kevin; Scholten, Donald J.; Russo, Scott S.; Easton, Kenneth J.; Steensma, Matthew R.

2014-01-01

Intervertebral disc (IVD) homeostasis is mediated through a combination of micro-environmental and biomechanical factors, all of which are subject to genetic influences. The aim of this study is to develop and characterize a genetically tractable, ex vivo organ culture model that can be used to further elucidate mechanisms of intervertebral disc disease. Specifically, we demonstrate that IVD disc explants (1) maintain their native phenotype in prolonged culture, (2) are responsive to exogenous stimuli, and (3) that relevant homeostatic regulatory mechanisms can be modulated through ex-vivo genetic recombination. We present a novel technique for isolation of murine IVD explants with demonstration of explant viability (CMFDA/propidium iodide staining), disc anatomy (H&E), maintenance of extracellular matrix (ECM) (Alcian Blue staining), and native expression profile (qRT-PCR) as well as ex vivo genetic recombination (mT/mG reporter mice; AdCre) following 14 days of culture in DMEM media containing 10% fetal bovine serum, 1% L-glutamine, and 1% penicillin/streptomycin. IVD explants maintained their micro-anatomic integrity, ECM proteoglycan content, viability, and gene expression profile consistent with a homeostatic drive in culture. Treatment of genetically engineered explants with cre-expressing adenovirus efficaciously induced ex vivo genetic recombination in a variety of genetically engineered mouse models. Exogenous administration of IL-1ß and TGF-ß3 resulted in predicted catabolic and anabolic responses, respectively. Genetic recombination of TGFBR1fl/fl explants resulted in constitutively active TGF-ß signaling that matched that of exogenously administered TGF-ß3. Our results illustrate the utility of the murine intervertebral disc explant to investigate mechanisms of intervertebral disc degeneration. PMID:25474689

Strain on intervertebral discs after anterior cervical decompression and fusion.

PubMed

Matsunaga, S; Kabayama, S; Yamamoto, T; Yone, K; Sakou, T; Nakanishi, K

1999-04-01

An analysis of the change in strain distribution of intervertebral discs present after anterior cervical decompression and fusion by an original method. The analytical results were compared to occurrence of herniation of the intervertebral disc on magnetic resonance imaging. To elucidate the influence of anterior cervical decompression and fusion on the unfused segments of the spine. There is no consensus regarding the exact significance of the biomechanical change in the unfused segment present after surgery. Ninety-six patients subjected to anterior cervical decompression and fusion for herniation of intervertebral discs were examined. Shear strain and longitudinal strain of intervertebral discs were analyzed on pre- and postoperative lateral dynamic routine radiography of the cervical spine. Thirty of the 96 patients were examined by magnetic resonance imaging before and after surgery, and the relation between alteration in strains and postsurgical occurrence of disc herniation was examined. In the cases of double- or triple-level fusion, shear strain of adjacent segments had increased 20% on average 1 year after surgery. Thirteen intervertebral discs that had an abnormally high degree of strain showed an increase in longitudinal strain after surgery. Eleven (85%) of the 13 discs that showed an abnormal increase in longitudinal strain had herniation in the same intervertebral discs with compression of the spinal cord during the follow-up period. Relief of symptoms was significantly poor in the patients with recent herniation. Close attention should be paid to long-term biomechanical changes in the unfused segment.

The analysis of axisymmetric viscoelasticity, time-dependent recovery, and hydration in rat tail intervertebral discs by radial compression test.

PubMed

Lin, Leou-Chyr; Hedman, Thomas P; Wang, Shyu-Jye; Huoh, Michael; Chang, Shih-Youeng

2009-05-01

The goal of this study was to develop a nondestructive radial compression technique and to investigate the viscoelastic behavior of the rat tail disc under repeated radial compression. Rat tail intervertebral disc underwent radial compression relaxation testing and creep testing using a custom-made gravitational creep machine. The axisymmetric viscoelasticity and time-dependent recovery were determined. Different levels of hydration (with or without normal saline spray) were supplied to evaluate the effect of changes in viscoelastic properties. Viscoelasticity was found to be axisymmetric in rat-tail intervertebral discs at four equidistant locations. Complete relaxation recovery was found to take 20 min, whereas creep recovery required 25 min. Hydration was required for obtaining viscoelastic axisymmetry and complete viscoelastic recovery.

Transcript Levels of Major Interleukins in Relation to the Clinicopathological Profile of Patients with Tuberculous Intervertebral Discs and Healthy Controls

PubMed Central

Liu, Chong; Zhan, Xinli; Xiao, Zengming; Fan, Qie; Deng, Li; Cui, Mingxing; Xiong, Chunxiang; Xue, Jingbo; Xie, Xiangtao

2014-01-01

Objectives The purpose of the present study was to simultaneously examine the transcript levels of a large number of interleukins (ILs; IL-9, IL-10, IL-12, IL-13, IL-16, IL-17, IL-18, IL-26, and IL-27) and investigate their correlation with the clinicopathological profiles of patients with tuberculous intervertebral discs. Methods Clinical data were collected from 150 patients participating in the study from January 2013 to December 2013. mRNA expression levels in 70 tuberculous, 70 herniated, and 10 control intervertebral disc specimens were determined by real-time polymerase chain reaction. Results IL-10, IL-16, IL-17, IL-18, and IL-27 displayed stronger expression in tuberculous spinal disc tissue than in normal intervertebral disc tissue (P<0.05). Our results illustrated multiple correlations among IL-10, IL-16, IL-17, IL-18, and IL-27 mRNA expression in tuberculous samples. Smoking habits were found to have a positive correlation with IL-17 transcript levels and a negative correlation with IL-10 transcript levels (P<0.05). Pain intensity, symptom duration, C-reactive protein levels, and the erythrocyte sedimentation rate exhibited multiple correlations with the transcript levels of several ILs (P<0.05). Conclusions The experimental data imply a double-sided effect on the activity of ILs in tuberculous spinal intervertebral discs, suggesting that they may be involved in intervertebral discs destruction. Our findings also suggest that smoking may affect the intervertebral discs destruction process of spinal tuberculosis. However, further studies are necessary to elucidate the exact role of ILs in the intervertebral discs destruction process of spinal tuberculosis. PMID:24971599

Development of Ultrasound to Measure In-vivo Dynamic Cervical Spine Intervertebral Disc Mechanics

DTIC Science & Technology

2015-01-01

1 AD_________ Award Number: W81XWH-13-1-0050 TITLE: Development of Ultrasound to Measure In-vivo Dynamic Cervical Spine Intervertebral Disc...COVERED 27 Dec 2013 - 26 Dec 2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Development of Ultrasound to Measure In-vivo Dynamic Cervical Spine...Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Neck pain is pervasive problems in military population

Separate the Sheep from the Goats: Use and Limitations of Large Animal Models in Intervertebral Disc Research.

PubMed

Reitmaier, Sandra; Graichen, Friedmar; Shirazi-Adl, Aboulfazl; Schmidt, Hendrik

2017-10-04

Approximately 5,168 large animals (pigs, sheep, goats, and cattle) were used for intervertebral disc research in identified studies published between 1985 and 2016. Most of the reviewed studies revealed a low scientific impact, a lack of sound justifications for the animal models, and a number of deficiencies in the documentation of the animal experimentation. The scientific community should take suitable measures to investigate the presumption that animal models have translational value in intervertebral disc research. Recommendations for future investigations are provided to improve the quality, validity, and usefulness of animal studies for intervertebral disc research. More in vivo studies are warranted to comprehensively evaluate the suitability of animal models in various applications and help place animal models as an integral, complementary part of intervertebral disc research.

LASER BIOLOGY AND MEDICINE: Effect of repetitive laser pulses on the electrical conductivity of intervertebral disc tissue

NASA Astrophysics Data System (ADS)

Omel'chenko, A. I.; Sobol', E. N.

2009-03-01

The thermomechanical effect of 1.56-μm fibre laser pulses on intervertebral disc cartilage has been studied using ac conductivity measurements with coaxial electrodes integrated with an optical fibre for laser radiation delivery to the tissue. The observed time dependences of tissue conductivity can be interpreted in terms of hydraulic effects and thermomechanical changes in tissue structure. The laserinduced changes in the electrical parameters of the tissue are shown to correlate with the structural changes, which were visualised using shadowgraph imaging. Local ac conductivity measurements in the bulk of tissue can be used to develop a diagnostic/monitoring system for laser regeneration of intervertebral discs.

Formation of the sacrum requires down-regulation of sonic hedgehog signaling in the sacral intervertebral discs.

PubMed

Bonavita, Raffaella; Vincent, Kathleen; Pinelli, Robert; Dahia, Chitra Lekha

2018-05-21

In humans, the sacrum forms an important component of the pelvic arch, and it transfers the weight of the body to the lower limbs. The sacrum is formed by collapse of the intervertebral discs (IVDs) between the five sacral vertebrae during childhood, and their fusion to form a single bone. We show that collapse of the sacral discs in the mouse is associated with the down-regulation of sonic hedgehog (SHH) signaling in the nucleus pulposus (NP) of the disc, and many aspects of this phenotype can be reversed by experimental postnatal activation of HH signaling. We have previously shown that SHH signaling is essential for the normal postnatal growth and differentiation of intervertebral discs elsewhere in the spine, and that loss of SHH signaling leads to pathological disc degeneration, a very common disorder of aging. Thus, loss of SHH is pathological in one region of the spine but part of normal development in another. © 2018. Published by The Company of Biologists Ltd.

Feasibility of minimally-invasive fiber-based evaluation of chondrodystrophoid canine intervertebral discs by light absorption and scattering spectroscopy

NASA Astrophysics Data System (ADS)

Jiang, Yuanyuan; McKeirnan, Kelci; Piao, Daqing; Bartels, Kenneth E.

2011-03-01

Extrusion or protrusion of an intervertebral disc is a common, frequently debilitating, painful, and sometimes fatal neurologic disease in the chondrodystrophic dog (dachshund, Pekingese, etc.). A similar condition of intervertebral disc degeneration with extrusion/protrusion is also a relatively common neurologic condition in human patients. Degeneration of the relatively avascular chondrodystrophoid intervertebral disc is associated with loss of water content, increased collagen, and deposits of calcified mineral in the nucleus pulposus. Current diagnostic methods have many limitations for providing accurate information regarding disc composition in situ prior to surgical intervention. Disc composition (i.e., mineralization), can influence the type of treatment regime and potentially prognosis and recurrence rates. The objective of this study is to investigate the feasibility of using a fiber-needle spectroscopy sensor to analyze the changes of tissue compositions involved in the chondrodystrophoid condition of the canine intervertebral disc. The nucleous pulposus, in which the metaplastic process / degeneration develops, is approximately 2mm thick and 5mm in diameter in the dachshund-sized dog. It lies in the center of the disc, surrounded by the annulus fibrosis and is enclosed by cartilaginous vertebral endplates cranially and caudally. This "shallow-and-small-slab" geometry limits the configuration of a fiber probe to sense the disc tissue volume without interference from the vertebrae. A single-fiber sensor is inserted into a 20 gauge myelographic spinal needle for insertion into the disc in situ and connected via a bifurcated fiber to the light source and a spectrometer. A tungsten light source and a 940nm light-emitting-diode are combined for spectral illumination covering VIS/NIR with expected improved sensitivity to water. Analysis of the reflectance spectra is expected to provide information of scattering and absorption compositions of tissue in proximity to the fiber-tip. Preliminary measurements on cadaveric canine intervertebral discs indicated significant reduction of scattering constituents and possible diminishment of water content after percutaneous laser disc ablation (PLDA). This fiber-needle based sensing configuration may be feasible for integrating the evaluation of calcification and water content into the work-flow of holmium:YAG laser disc ablation for pre-operative in-line detection and post-operative evaluation of therapeutic interventions regarding the chondrodystrophic disc.

In vivo biofunctional evaluation of hydrogels for disc regeneration.

PubMed

Reitmaier, Sandra; Kreja, Ludwika; Gruchenberg, Katharina; Kanter, Britta; Silva-Correia, Joana; Oliveira, Joaquim Miguel; Reis, Rui Luís; Perugini, Valeria; Santin, Matteo; Ignatius, Anita; Wilke, Hans-Joachim

2014-01-01

Regenerative strategies aim to restore the original biofunctionality of the intervertebral disc. Different biomaterials are available, which might support disc regeneration. In the present study, the prospects of success of two hydrogels functionalized with anti-angiogenic peptides and seeded with bone marrow derived mononuclear cells (BMC), respectively, were investigated in an ovine nucleotomy model. In a one-step procedure iliac crest aspirates were harvested and, subsequently, separated BMC were seeded on hydrogels and implanted into the ovine disc. For the cell-seeded approach a hyaluronic acid-based hydrogel was used. The anti-angiogenic potential of newly developed VEGF-blockers was investigated on ionically crosslinked metacrylated gellan gum hydrogels. Untreated discs served as nucleotomy controls. 24 adult merino sheep were used. After 6 weeks histological, after 12 weeks histological and biomechanical analyses were conducted. Biomechanical tests revealed no differences between any of the implanted and nucleotomized discs. All implanted discs significantly degenerated compared to intact discs. In contrast, there was no marked difference between implanted and nucleotomized discs. In tendency, albeit not significant, degeneration score and disc height index deteriorated for all but not for the cell-seeded hydrogels from 6 to 12 weeks. Cell-seeded hydrogels slightly decelerated degeneration. None of the hydrogel configurations was able to regenerate biofunctionality of the intervertebral disc. This might presumably be caused by hydrogel extrusion. Great importance should be given to the development of annulus sealants, which effectively exploit the potential of (cell-seeded) hydrogels for biological disc regeneration and restoration of intervertebral disc functioning.

Notochordal cells in the adult intervertebral disc: new perspective on an old question.

PubMed

Risbud, Makarand V; Shapiro, Irving M

2011-01-01

The intervertebral disc is a tissue positioned between each of the vertebrae that accommodates applied biomechanical forces to the spine. The central compartment of the disc contains the nucleus pulposus (NP) which is enclosed by the annulus fibrosus and the endplate cartilage.The NP is derived from the notochord, a rod-like structure of mesodermal origin. Development of the notochord is tightly regulated by interactive transcription factors and target genes. Since a number of these molecules are unique they have be used for cell lineage and fate mapping studies of tissues of the intervertebral disc. These studies have shown that in a number of species including human, NP tissue retains notochordal cells throughout life. In the adult NP, there are present both large and small notochordal cells, as well as a progenitor cell population which can differentiate along the mesengenic pathway. Since tissue renewal in the intervertebral disc is dependent on the ability of these cells to commit to the NP lineage and undergo terminal differentiation, studies have been performed to assess which signaling pathways may regulate these activities. The notch signaling pathway is active in the intervertebral disc and is responsive to hypoxia, probably through HIF-1a. From a disease viewpoint, it is hypothesized that an oxemic shift, possibly mediated by alterations in the vascular supply to the tissues of the disc would be expected to lead to a failure in notochordal progenitor cell activation and a decrease in the number of differentiated cells. In turn, this would lead to decrements in function and enhancement of the effect of agents that are known to promote disc degeneration.

Canine pancreatic lipase immunoreactivity concentrations associated with intervertebral disc disease in 84 dogs.

PubMed

Schueler, R O; White, G; Schueler, R L; Steiner, J M; Wassef, A

2018-05-01

To determine the differences in serum canine pancreatic lipase immunoreactivity between dogs with intervertebral disc herniation and healthy control dogs. Eighty-four client-owned dogs with intervertebral disc herniation, diagnosed by neurologic examination and imaging, and 18 healthy control dogs. Samples of whole blood were collected within 90 minutes of admission. Serum canine pancreatic lipase immunoreactivity concentrations were measured by a commercial immunoassay and evaluated for association with intervertebral disc herniation, signalment, neurolocalisation and the preadmission administration of glucocorticosteriods or non-steroidal anti-inflammatory drugs. Serum canine pancreatic lipase immunoreactivity concentrations were statistically increased in dogs with intervertebral disc herniation (P<0·01, n=38). A subgroup of dogs (19/38) with elevated canine pancreatic lipase immunoreactivity concentrations was re-evaluated between 2 and 4 weeks later, and 15 had resolution of clinical signs and values less than 200 μg/L. Serum canine pancreatic lipase immunoreactivity concentrations were not significantly correlated with clinical gastrointestinal disease, neurolocalisation or the preadmission administration of corticosteroids or non-steroidal anti-inflammatory drugs. These results suggest that serum canine pancreatic lipase immunoreactivity concentrations are significantly elevated in dogs with intervertebral disc herniation. © 2018 British Small Animal Veterinary Association.

Determination of the intervertebral disc space from CT images of the lumbar spine

NASA Astrophysics Data System (ADS)

Korez, Robert; Å tern, Darko; Likar, Boštjan; Pernuš, Franjo; Vrtovec, Tomaž

2014-03-01

Degenerative changes of the intervertebral disc are among the most common causes of low back pain, where for individuals with significant symptoms surgery may be needed. One of the interventions is the total disc replacement surgery, where the degenerated disc is replaced by an artificial implant. For designing implants with good bone contact and continuous force distribution, the morphology of the intervertebral disc space and vertebral body endplates is of considerable importance. In this study we propose a method for the determination of the intervertebral disc space from three-dimensional (3D) computed tomography (CT) images of the lumbar spine. The first step of the proposed method is the construction of a model of vertebral bodies in the lumbar spine. For this purpose, a chain of five elliptical cylinders is initialized in the 3D image and then deformed to resemble vertebral bodies by introducing 25 shape parameters. The parameters are obtained by aligning the chain to the vertebral bodies in the CT image according to image intensity and appearance information. The determination of the intervertebral disc space is finally achieved by finding the planes that fit the endplates of the obtained parametric 3D models, and placing points in the space between the planes of adjacent vertebrae that enable surface reconstruction of the intervertebral disc space. The morphometric analysis of images from 20 subjects yielded 11:3 +/- 2:6, 12:1 +/- 2:4, 12:8 +/- 2:0 and 12:9 +/- 2:7 cm3 in terms of L1-L2, L2-L3, L3-L4 and L4-L5 intervertebral disc space volume, respectively.

Hedgehog signaling is required for formation of the notochord sheath and patterning of nuclei pulposi within the intervertebral discs

PubMed Central

Choi, Kyung-Suk; Harfe, Brian D.

2011-01-01

The vertebrae notochord is a transient rod-like structure that produces secreted factors that are responsible for patterning surrounding tissues. During later mouse embryogenesis, the notochord gives rise to the middle part of the intervertebral disc, called the nucleus pulposus. Currently, very little is known about the molecular mechanisms responsible for forming the intervertebral discs. Here we demonstrate that hedgehog signaling is required for formation of the intervertebral discs. Removal of hedgehog signaling in the notochord and nearby floorplate resulted in the formation of an aberrant notochord sheath that normally surrounds this structure. In the absence of the notochord sheath, small nuclei pulposi were formed, with most notochord cells dispersed throughout the vertebral bodies during embryogenesis. Our data suggest that the formation of the notochord sheath requires hedgehog signaling and that the sheath is essential for maintaining the rod-like structure of the notochord during early embryonic development. As notochord cells form nuclei pulposi, we propose that the notochord sheath functions as a “wrapper” around the notochord to constrain these cells along the vertebral column. PMID:21606373

Hedgehog signaling is required for formation of the notochord sheath and patterning of nuclei pulposi within the intervertebral discs.

PubMed

Choi, Kyung-Suk; Harfe, Brian D

2011-06-07

The vertebrae notochord is a transient rod-like structure that produces secreted factors that are responsible for patterning surrounding tissues. During later mouse embryogenesis, the notochord gives rise to the middle part of the intervertebral disc, called the nucleus pulposus. Currently, very little is known about the molecular mechanisms responsible for forming the intervertebral discs. Here we demonstrate that hedgehog signaling is required for formation of the intervertebral discs. Removal of hedgehog signaling in the notochord and nearby floorplate resulted in the formation of an aberrant notochord sheath that normally surrounds this structure. In the absence of the notochord sheath, small nuclei pulposi were formed, with most notochord cells dispersed throughout the vertebral bodies during embryogenesis. Our data suggest that the formation of the notochord sheath requires hedgehog signaling and that the sheath is essential for maintaining the rod-like structure of the notochord during early embryonic development. As notochord cells form nuclei pulposi, we propose that the notochord sheath functions as a "wrapper" around the notochord to constrain these cells along the vertebral column.

Evaluation of T2-weighted versus short-tau inversion recovery sagittal sequences in the identification and localization of canine intervertebral disc extrusion with low-field magnetic resonance imaging.

PubMed

Housley, Daniel; Caine, Abby; Cherubini, Giunio; Taeymans, Olivier

2017-07-01

Sagittal T2-weighted sequences (T2-SAG) are the foundation of spinal protocols when screening for the presence of intervertebral disc extrusion. We often utilize sagittal short-tau inversion recovery sequences (STIR-SAG) as an adjunctive screening series, and experience suggests that this combined approach provides superior detection rates. We hypothesized that STIR-SAG would provide higher sensitivity than T2-SAG in the identification and localization of intervertebral disc extrusion. We further hypothesized that the parallel evaluation of paired T2-SAG and STIR-SAG series would provide a higher sensitivity than could be achieved with either independent sagittal series when viewed in isolation. This retrospective diagnostic accuracy study blindly reviewed T2-SAG and STIR-SAG sequences from dogs (n = 110) with surgically confirmed intervertebral disc extrusion. A consensus between two radiologists found no significant difference in sensitivity between T2-SAG and STIR-SAG during the identification of intervertebral disc extrusion (T2-SAG: 92.7%, STIR-SAG: 94.5%, P = 0.752). Nevertheless, STIR-SAG accurately identified intervertebral disc extrusion in 66.7% of cases where the evaluation of T2-SAG in isolation had provided a false negative diagnosis. Additionally, one radiologist found that the parallel evaluation of paired T2-SAG and STIR-SAG series provided a significantly higher sensitivity than T2-SAG in isolation, during the identification of intervertebral disc extrusion (T2-SAG: 78.2%, paired T2-SAG, and STIR-SAG: 90.9%, P = 0.017). A similar nonsignificant trend was observed when the consensus of both radiologists was taken into consideration (T2-SAG: 92.7%, paired T2-SAG, and STIR-SAG = 97.3%, P = 0.392). We therefore conclude that STIR-SAG is capable of identifying intervertebral disc extrusion that is inconspicuous in T2-SAG, and that STIR-SAG should be considered a useful adjunctive sequence during preliminary sagittal screening for intervertebral disc extrusion in low-field magnetic resonance. © 2017 American College of Veterinary Radiology.

MECHANICAL DESIGN CRITERIA FOR INTERVERTEBRAL DISC TISSUE ENGINEERING

PubMed Central

Nerurkar, Nandan L.; Elliott, Dawn M.; Mauck, Robert L.

2009-01-01

Due to the inability of current clinical practices to restore function to degenerated intervertebral discs, the arena of disc tissue engineering has received substantial attention in recent years. Despite tremendous growth and progress in this field, translation to clinical implementation has been hindered by a lack of well-defined functional benchmarks. Because successful replacement of the disc is contingent upon replication of some or all of its complex mechanical behaviour, it is critically important that disc mechanics be well characterized in order to establish discrete functional goals for tissue engineering. In this review, the key functional signatures of the intervertebral disc are discussed and used to propose a series of native tissue benchmarks to guide the development of engineered replacement tissues. These benchmarks include measures of mechanical function under tensile, compressive and shear deformations for the disc and its substructures. In some cases, important functional measures are identified that have yet to be measured in the native tissue. Ultimately, native tissue benchmark values are compared to measurements that have been made on engineered disc tissues, identifying measures where functional equivalence was achieved, and others where there remain opportunities for advancement. Several excellent reviews exist regarding disc composition and structure, as well as recent tissue engineering strategies; therefore this review will remain focused on the functional aspects of disc tissue engineering. PMID:20080239

CT morphometry of adult thoracic intervertebral discs.

PubMed

Fletcher, Justin G R; Stringer, Mark D; Briggs, Christopher A; Davies, Tilman M; Woodley, Stephanie J

2015-10-01

Despite being commonly affected by degenerative disorders, there are few data on normal thoracic intervertebral disc dimensions. A morphometric analysis of adult thoracic intervertebral discs was, therefore, undertaken. Archival computed tomography scans of 128 recently deceased individuals (70 males, 58 females, 20-79 years) with no known spinal pathology were analysed to determine thoracic disc morphometry and variations with disc level, sex and age. Reliability was assessed by intraclass correlation coefficients (ICCs). Anterior and posterior intervertebral disc heights and axial dimensions were significantly greater in men (anterior disc height 4.0±1.4 vs 3.6±1.3 mm; posterior disc height 3.6±0.90 vs 3.4±0.93 mm; p<0.01). Disc heights and axial dimensions at T4-5 were similar or smaller than at T2-3, but thereafter increased caudally (mean anterior disc height T4-5 and T10-11, 2.7±0.7 and 5.4±1.2 mm, respectively, in men; 2.6±0.8 and 5.1±1.3 mm, respectively, in women; p<0.05). Except at T2-3, anterior disc height decreased with advancing age and anteroposterior and transverse disc dimensions increased; posterior and middle disc heights and indices of disc shape showed no consistent statistically significant changes. Most parameters showed substantial to almost perfect agreement for intra- and inter-rater reliability. Thoracic disc morphometry varies significantly and consistently with disc level, sex and age. This study provides unique reference data on adult thoracic intervertebral disc morphometry, which may be useful when interpreting pathological changes and for future biomechanical and functional studies.

Overview: the role of Propionibacterium acnes in nonpyogenic intervertebral discs.

PubMed

Chen, Zhe; Cao, Peng; Zhou, Zezhu; Yuan, Ye; Jiao, Yucheng; Zheng, Yuehuan

2016-06-01

Propionibacterium acnes (P. acnes), an important opportunistic anaerobic Gram-positive bacterium, causes bone and joint infections, discitis and spondylodiscitis. Accumulated evidence suggested that this microbe can colonise inside intervertebral discs without causing symptoms of discitis. Epidemiological investigation shows that the prevalence ranges from 13 % to 44 %. Furthermore, colonisation by P. acnes inside nonpyogenic intervertebral discs is thought to be one pathogen causing sciatica, Modic changes and nonspecific low back pain. Specially, patients can attain significant relief of low back pain, amelioration of Modic changes and alleviation of sciatica after antibiotic therapy, indicating the role of P. acnes in these pathological changes. However, until now, there were hypotheses only to explain problems such as how P. acnes access intervertebral discs and what the exact pathological mechanism it employs during its latent infection period. In addition, research regarding diagnostic procedures and treatment strategies were also rare. Overall, the prevalence and possible pathological role that P. acnes plays inside nonpyogenic intervertebral discs is summarised in this paper.

Measurement of occlusion of the spinal canal and intervertebral foramen by intervertebral disc bulge

PubMed Central

Cuchanski, Mathieu; Cook, Daniel; Whiting, Donald M.; Cheng, Boyle C.

2011-01-01

Background Disc protrusion has been proposed to be a possible cause of both pain and stenosis in the lower spine. No previous study has described the amount of disc occlusion of the spinal canal and intervertebral foramen that occurs under different loading conditions. The objective of this study was to quantitatively assess the percent occlusion of the spinal canal and intervertebral foramen by disc bulge under different loading conditions. Methods Spinal canal depth and foraminal width were measured on computed tomography–scanned images of 7 human lumbar spine specimens. In vitro disc bulge measurements were completed by use of a previously described method in which single functional spinal units were subjected to 3 separate load protocols in a spine test machine and disc bulge was recorded with an optoelectric motion system that tracked active light-emitting diodes placed on the posterior and posterolateral aspects of the intervertebral disc. Occlusion was defined as percentage of encroachment into area of interest by maximum measured disc bulge at corresponding point of interest (the spinal canal is at the posterior point; the intervertebral foramen is at the posterolateral point). Results The mean spinal canal depth and mean foraminal width were 19 4 ± mm and 5 ± 2 mm, respectively. Mean spinal canal occlusion under a 250-N axial load, ± 2.5 Nm of flexion/extension, and ± 2.5 Nm of lateral bend was 2.5% ± 1.9%, 2.5% ± 1.6%, and 1.5% ± 0.8%, respectively. Mean intervertebral foramen occlusion under a 250-N axial load, ± 2.5 Nm of flexion/extension, and ± 2.5 Nm of lateral bend was 7.8% ± 4.7%, 9.5% ± 5.7%, and 11.3% ± 6.2%, respectively. Conclusion Percent occlusion of the spinal canal and intervertebral foramen is dependent on magnitude and direction of load. Exiting neural elements at the location of the intervertebral foramen are the most vulnerable to impingement and generation of pain. PMID:25802663

A 1-D model of the nonlinear dynamics of the human lumbar intervertebral disc

NASA Astrophysics Data System (ADS)

Marini, Giacomo; Huber, Gerd; Püschel, Klaus; Ferguson, Stephen J.

2017-01-01

Lumped parameter models of the spine have been developed to investigate its response to whole body vibration. However, these models assume the behaviour of the intervertebral disc to be linear-elastic. Recently, the authors have reported on the nonlinear dynamic behaviour of the human lumbar intervertebral disc. This response was shown to be dependent on the applied preload and amplitude of the stimuli. However, the mechanical properties of a standard linear elastic model are not dependent on the current deformation state of the system. The aim of this study was therefore to develop a model that is able to describe the axial, nonlinear quasi-static response and to predict the nonlinear dynamic characteristics of the disc. The ability to adapt the model to an individual disc's response was a specific focus of the study, with model validation performed against prior experimental data. The influence of the numerical parameters used in the simulations was investigated. The developed model exhibited an axial quasi-static and dynamic response, which agreed well with the corresponding experiments. However, the model needs further improvement to capture additional peculiar characteristics of the system dynamics, such as the change of mean point of oscillation exhibited by the specimens when oscillating in the region of nonlinear resonance. Reference time steps were identified for specific integration scheme. The study has demonstrated that taking into account the nonlinear-elastic behaviour typical of the intervertebral disc results in a predicted system oscillation much closer to the physiological response than that provided by linear-elastic models. For dynamic analysis, the use of standard linear-elastic models should be avoided, or restricted to study cases where the amplitude of the stimuli is relatively small.

Is there any relationship between proinflammatory mediator levels in disc material and myelopathy with cervical disc herniation and spondylosis? A non-randomized, prospective clinical study

PubMed Central

Asir, Alparslan; Cetinkal, Ahmet; Gedik, Nursal; Kutlay, Ahmet Murat; Çolak, Ahmet; Kurtar, Sedat; Simsek, Hakan

2007-01-01

The proinflammatory mediator (PIM) levels were assessed in surgically removed samples of herniated cervical intervertebral discs. The objective of this study was to investigate if there is a correlation between the levels of PIMs in disc material and myelopathy associated with cervical intervertebral disc herniation and spondylosis. The role of proinflammatory mediators in the degeneration of intervertebral disc and the inflammatory effects of disc herniations on radicular pain has been previously published. However, the possible relationship between PIMs and myelopathy related to cervical disc herniation and spondylosis has not been investigated before. Thirty-two patients undergoing surgery for cervical disc herniation and spondylosis were investigated. Surgically obtained disc materials, stored at 70°C, were classified into two groups: cervical disc herniation alone or with myelopathy. Biochemical preparation and solid phase enzyme amplified sensitivity immunoassay (ELISIA) analysis of the samples were performed to assess the concentration of mediators in the samples. Very similar values of interleukin-6 were found in both groups whereas the concentrations of mediators were significantly higher in myelopathy group. This study has demonstrated that PIMs are involved in cervical intervertebral disc degeneration with higher concentrations in the samples associated with myelopathy. PMID:17476536

Sonic hedgehog in the notochord is sufficient for patterning of the intervertebral discs

PubMed Central

Choi, Kyung-Suk; Lee, Chanmi; Harfe, Brian D.

2012-01-01

The intervertebral discs, located between adjacent vertebrae, are required for stability of the spine and distributing mechanical load throughout the vertebral column. All cell types located in thes middle regions of the discs, called nuclei pulposi, are derived from the embryonic notochord. Recently, it was shown that the hedgehog signaling pathway plays an essential role during formation of nuclei pulposi. However, during the time that nuclei pulposi are forming, Shh is expressed in both the notochord and the nearby floor plate. To determine the source of SHH protein sufficient for formation of nuclei pulposi we removed Shh from either the floor plate or the notochord using tamoxifen-inducible Cre alleles. Removal of Shh from the floor plate resulted in phenotypically normal intervertebral discs, indicating that Shh expression in this tissue is not required for disc patterning. In addition, embryos that lacked Shh in the floor plate had normal vertebral columns, demonstrating that Shh expression in the notochord is sufficient for pattering the entire vertebral column. Removal of Shh from the notochord resulted in the absence of Shh in the floor plate, loss of intervertebral discs and vertebral structures. These data indicate that Shh expression in the notochord is sufficient for patterning of the intervertebral discs and the vertebral column. PMID:22841806

Sonic hedgehog in the notochord is sufficient for patterning of the intervertebral discs.

PubMed

Choi, Kyung-Suk; Lee, Chanmi; Harfe, Brian D

2012-01-01

The intervertebral discs, located between adjacent vertebrae, are required for stability of the spine and distributing mechanical load throughout the vertebral column. All cell types located in the middle regions of the discs, called nuclei pulposi, are derived from the embryonic notochord. Recently, it was shown that the hedgehog signaling pathway plays an essential role during formation of nuclei pulposi. However, during the time that nuclei pulposi are forming, Shh is expressed in both the notochord and the nearby floor plate. To determine the source of SHH protein sufficient for formation of nuclei pulposi we removed Shh from either the floor plate or the notochord using tamoxifen-inducible Cre alleles. Removal of Shh from the floor plate resulted in phenotypically normal intervertebral discs, indicating that Shh expression in this tissue is not required for disc patterning. In addition, embryos that lacked Shh in the floor plate had normal vertebral columns, demonstrating that Shh expression in the notochord is sufficient for pattering the entire vertebral column. Removal of Shh from the notochord resulted in the absence of Shh in the floor plate, loss of intervertebral discs and vertebral structures. These data indicate that Shh expression in the notochord is sufficient for patterning of the intervertebral discs and the vertebral column. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Small vertebral cross-sectional area and tall intervertebral disc in adolescent idiopathic scoliosis.

PubMed

Ponrartana, Skorn; Fisher, Carissa L; Aggabao, Patricia C; Chavez, Thomas A; Broom, Alexander M; Wren, Tishya A L; Skaggs, David L; Gilsanz, Vicente

2016-09-01

When compared to boys, girls have smaller vertebral cross-sectional area, which conveys a greater spinal flexibility, and a higher prevalence of adolescent idiopathic scoliosis. To test the hypothesis that small vertebral cross-sectional area and tall intervertebral disc height are structural characteristics of patients with adolescent idiopathic scoliosis. Using multiplanar imaging techniques, measures of vertebral cross-sectional area, vertebral height and intervertebral disc height in the lumbar spine were obtained in 35 pairs of girls and 11 pairs of boys with and without adolescent idiopathic scoliosis of the thoracic spine matched for age, height and weight. Compared to adolescents without spinal deformity, girls and boys with adolescent idiopathic scoliosis had, on average, 9.8% (6.68 ± 0.81 vs. 7.40 ± 0.99 cm(2); P = 0.0007) and 13.9% (8.22 ± 0.84 vs. 9.55 ± 1.61 cm(2); P = 0.009) smaller vertebral cross-sectional dimensions, respectively. Additionally, patients with adolescent idiopathic scoliosis had significantly greater values for intervertebral disc heights (9.06 ± 0.85 vs. 7.31 ± 0.62 mm and 9.09 ± 0.87 vs. 7.61 ± 1.00 mm for girls and boys respectively; both P ≤ 0.011). Multiple regression analysis indicated that the presence of scoliosis was negatively associated with vertebral cross-sectional area and positively with intervertebral disc height, independent of sex, age and body mass index. We provide new evidence that girls and boys with adolescent idiopathic scoliosis have significantly smaller vertebral cross-sectional area and taller intervertebral disc heights - two major structural determinants that influence trunk flexibility. With appropriate validation, these findings may have implications for the identification of children at the highest risk for developing scoliosis.

Changes in intervertebral disc cross-sectional area with bed rest and space flight

NASA Technical Reports Server (NTRS)

LeBlanc, A. D.; Evans, H. J.; Schneider, V. S.; Wendt, R. E. 3rd; Hedrick, T. D.

1994-01-01

STUDY DESIGN. We measured the cross-sectional area of the intervertebral discs of normal volunteers after an overnight rest; before, during, and after 5 or 17 weeks of bed rest; and before and after 8 days of weightlessness. OBJECTIVES. This study sought to determine the degree of expansion of the lumbar discs resulting from bed rest and space flight. SUMMARY OF BACKGROUND DATA. Weightlessness and bed rest, an analog for weightlessness, reduce the mechanical loading on the musculoskeletal system. When unloaded, intervertebral discs will expand, increasing the nutritional diffusion distance and altering the mechanical properties of the spine. METHODS. Magnetic resonance imaging was used to measure the cross-sectional area and transverse relaxation time (T2) of the intervertebral discs. RESULTS. Overnight or longer bed rest causes expansion of the disc area, which reaches an equilibrium value of about 22% (range 10-40%) above baseline within 4 days. Increases in disc area were associated with modest increases in disc T2. During bed rest, disc height increased approximately 1 mm, about one-half of previous estimates based on body height measurements. After 5 weeks of bed rest, disc area returned to baseline within a few days of ambulation, whereas after 17 weeks, disc area remained above baseline 6 weeks after reambulation. After 8 days of weightlessness, T2, disc area, and lumbar length were not significantly different from baseline values 24 hours after landing. CONCLUSIONS. Significant adaptive changes in the intervertebral discs can be expected during weightlessness. These changes, which are rapidly reversible after short-duration flights, may be an important factor during and after long-duration missions.

Mechanical design criteria for intervertebral disc tissue engineering.

PubMed

Nerurkar, Nandan L; Elliott, Dawn M; Mauck, Robert L

2010-04-19

Due to the inability of current clinical practices to restore function to degenerated intervertebral discs, the arena of disc tissue engineering has received substantial attention in recent years. Despite tremendous growth and progress in this field, translation to clinical implementation has been hindered by a lack of well-defined functional benchmarks. Because successful replacement of the disc is contingent upon replication of some or all of its complex mechanical behaviors, it is critically important that disc mechanics be well characterized in order to establish discrete functional goals for tissue engineering. In this review, the key functional signatures of the intervertebral disc are discussed and used to propose a series of native tissue benchmarks to guide the development of engineered replacement tissues. These benchmarks include measures of mechanical function under tensile, compressive, and shear deformations for the disc and its substructures. In some cases, important functional measures are identified that have yet to be measured in the native tissue. Ultimately, native tissue benchmark values are compared to measurements that have been made on engineered disc tissues, identifying where functional equivalence was achieved, and where there remain opportunities for advancement. Several excellent reviews exist regarding disc composition and structure, as well as recent tissue engineering strategies; therefore this review will remain focused on the functional aspects of disc tissue engineering. Copyright 2009 Elsevier Ltd. All rights reserved.

Developmental mechanisms of intervertebral disc and vertebral column formation.

PubMed

Lawson, Lisa Y; Harfe, Brian D

2017-11-01

The vertebral column consists of repeating units of ossified vertebrae that are adjoined by fibrocartilagenous intervertebral discs. These structures form from the embryonic notochord and somitic mesoderm. In humans, congenital malformations of the vertebral column include scoliosis, kyphosis, spina bifida, and Klippel Feil syndrome. In adulthood, a common malady affecting the vertebral column includes disc degeneration and associated back pain. Indeed, recent reports estimate that low back pain is the number one cause of disability worldwide. Our review provides an overview of the molecular mechanisms underlying vertebral column morphogenesis and intervertebral disc development and maintenance, with an emphasis on what has been gleaned from recent genetic studies in mice. The aim of this review is to provide a developmental framework through which vertebral column formation can be understood so that ultimately, research scientists and clinicians alike can restore disc health with appropriately designed gene and cell-based therapies. WIREs Dev Biol 2017, 6:e283. doi: 10.1002/wdev.283 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

Human Amniotic Tissue-derived Allograft, NuCel, in Posteriolateral Lumbar Fusions for Degenerative Disc Disease

ClinicalTrials.gov

2017-09-14

Lumbar Degenerative Disc Disease; Spinal Stenosis; Spondylolisthesis; Spondylosis; Intervertebral Disk Displacement; Intervertebral Disk Degeneration; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Spondylolysis

A meta-model analysis of a finite element simulation for defining poroelastic properties of intervertebral discs.

PubMed

Nikkhoo, Mohammad; Hsu, Yu-Chun; Haghpanahi, Mohammad; Parnianpour, Mohamad; Wang, Jaw-Lin

2013-06-01

Finite element analysis is an effective tool to evaluate the material properties of living tissue. For an interactive optimization procedure, the finite element analysis usually needs many simulations to reach a reasonable solution. The meta-model analysis of finite element simulation can be used to reduce the computation of a structure with complex geometry or a material with composite constitutive equations. The intervertebral disc is a complex, heterogeneous, and hydrated porous structure. A poroelastic finite element model can be used to observe the fluid transferring, pressure deviation, and other properties within the disc. Defining reasonable poroelastic material properties of the anulus fibrosus and nucleus pulposus is critical for the quality of the simulation. We developed a material property updating protocol, which is basically a fitting algorithm consisted of finite element simulations and a quadratic response surface regression. This protocol was used to find the material properties, such as the hydraulic permeability, elastic modulus, and Poisson's ratio, of intact and degenerated porcine discs. The results showed that the in vitro disc experimental deformations were well fitted with limited finite element simulations and a quadratic response surface regression. The comparison of material properties of intact and degenerated discs showed that the hydraulic permeability significantly decreased but Poisson's ratio significantly increased for the degenerated discs. This study shows that the developed protocol is efficient and effective in defining material properties of a complex structure such as the intervertebral disc.

Discography (Discogram)

MedlinePlus

... help guide the treatment of abnormal intervertebral discs – sponge-like cushions located between the vertebrae of the ... the source of back pain. Intervertebral discs are sponge-like cushions between the vertebrae , or bones, of ...

Physical examination, magnetic resonance image, and electrodiagnostic study in patients with lumbosacral disc herniation or spinal stenosis.

PubMed

Lee, Jung Hwan; Lee, Sang-Ho

2012-10-01

To compare the clinical implications of electro-diagnostic study with those of magnetic resonance imaging in patients with lumbosacral intervertebral herniated disc or spinal stenosis. Retrospective study of clinical data. Patients with lumbosacral intervertebral herniated disc or spinal stenosis, diagnosed by clinical assessment and magnetic resonance imaging (MRI), were selected. A total of 753 patients (437 with lumbosacral intervertebral herniated disc and 316 with spinal stenosis) were included in the study. Clinical data for electrodiagnostic study (EDX)and MRI were compared and the sensitivity and specificity of these studies were evaluated. Among all subjects, 267 had radiculopathy on EDX (EDX (+)) and 486 no radiculopathy (EDX(-)). Furthermore, 391 had root compression on MRI (MRI (+)) and 362 no root compression on MRI (MRI (-)). Patients with radioculopathy on EDX (+) showed a significantly higher visual analogue scale score for radiating pain and a higher Oswestry Disability Index than those with negative findings by EDX (-) in the total subjects group and the lumbosacral intervertebral herniated disc subgroup, and there was a trend toward higher Oswestry Disability Index in the spinal stenosis subgroup. Although patients with radioculopathy on root compression on MRI (+) also had a higher visual analogue scale for radiating pain than patients with negative findings by MRI (-) in the total subjects group and the lumbosacral intervertebral herniated disc subgroup, no significant difference was seen in the Oswestry Disability Index. EDX revealed a significant correlation with muscle weakness in the total subjects group and the lumbosacral intervertebral herniated disc subgroup, and trends toward muscle weakness in the spinal stenosis subgroup, whereas there was no such significant correlation for MRI findings in any group. Electrodiagnostic study had a higher specificity in terms of physical examination data than MRI, in spite of its lower sensitivity. Electrodiagnostic study was significantly more correlated with clinical data, especially leg muscle weakness and functional status, and showed a higher specificity than MRI in patients with lumbosacral intervertebral herniated disc or spinal stenosis.

Histological Identification of Propionibacterium acnes in Nonpyogenic Degenerated Intervertebral Discs.

PubMed

Yuan, Ye; Zhou, Zezhu; Jiao, Yucheng; Li, Changwei; Zheng, Yuehuan; Lin, Yazhou; Xiao, Jiaqi; Chen, Zhe; Cao, Peng

2017-01-01

Purpose . Low-virulence anaerobic bacteria, especially the Propionibacterium acnes (P. acnes) , have been thought to be a new pathogeny for a series of disc diseases. However, until now, there has been no histological evidence to confirm this link. The purpose of this study was to confirm the presence of P. acnes in nonpyogenic intervertebral discs via histological observation. Method . Degenerated intervertebral discs were harvested from 76 patients with low back pain and/or sciatica but without any symptoms of discitis or spondylodiscitis. The samples were cultured under anaerobic conditions and then examined using 16S rDNA PCR to screen for P. acnes . Samples found to be positive for P. acnes were stained with hematoxylin-eosin (HE) and modified Brown-Brenn staining and observed under a microscope. Results . Here, 16 intervertebral discs were found to be positive for P. acnes via 16S rDNA PCR and the prevalence was 21.05% (16/76). Among them, 7 samples had visible microbes stained with HE and modified Brown-Brenn staining. Morphological examination showed the bacteria to be Gram-positive and rod-shaped, so they were considered P. acnes . Conclusion . P. acnes is capable of colonizing some degenerated intervertebral discs without causing discitis, and its presence could be further confirmed by histological evidence. Targeting these bacteria may be a promising therapy method for some disc diseases.

Geometry of the intervertebral volume and vertebral endplates of the human spine.

PubMed

van der Houwen, E B; Baron, P; Veldhuizen, A G; Burgerhof, J G M; van Ooijen, P M A; Verkerke, G J

2010-01-01

Replacement of a degenerated vertebral disc with an artificial intervertebral disc (AID) is currently possible, but poses problems, mainly in the force distribution through the vertebral column. Data on the intervertebral disc space geometry will provide a better fit of the prosthesis to the vertebrae, but current literature on vertebral disc geometry is very scarce or not suitable. In this study, existing CT-scans of 77 patients were analyzed to measure the intervertebral disc and vertebral endplate geometry of the lumbar spine. Ten adjacent points on both sides of the vertebrae (S1-superior to T12-inferior) and sagittal and transverse diameters were measured to describe the shape of the caudal and cranial vertebral planes of the vertebrae. It was found that the largest endplate depth is located in the middle or posterior regions of the vertebra, that there is a linear relationship between all inferior endplate depths and the endplate location (p < 0.0001) within the spinal column, and that the superior endplate depth increases with age by about 0.01 mm per year (p < 0.02). The wedge angle increases from T12-L1 to L5-S1. The results allow for improvement of the fit of intervertebral disc-prostheses to the vertebrae and optimized force transmission through the vertebral column.

Localization of the lumbar discs using machine learning and exact probabilistic inference.

PubMed

Oktay, Ayse Betul; Akgul, Yusuf Sinan

2011-01-01

We propose a novel fully automatic approach to localize the lumbar intervertebral discs in MR images with PHOG based SVM and a probabilistic graphical model. At the local level, our method assigns a score to each pixel in target image that indicates whether it is a disc center or not. At the global level, we define a chain-like graphical model that represents the lumbar intervertebral discs and we use an exact inference algorithm to localize the discs. Our main contributions are the employment of the SVM with the PHOG based descriptor which is robust against variations of the discs and a graphical model that reflects the linear nature of the vertebral column. Our inference algorithm runs in polynomial time and produces globally optimal results. The developed system is validated on a real spine MRI dataset and the final localization results are favorable compared to the results reported in the literature.

Investigation of biomechanical behavior of lumbar vertebral segments with dynamic stabilization device using finite element approach

NASA Astrophysics Data System (ADS)

Deoghare, Ashish B.; Kashyap, Siddharth; Padole, Pramod M.

2013-03-01

Degenerative disc disease is a major source of lower back pain and significantly alters the biomechanics of the lumbar spine. Dynamic stabilization device is a remedial technique which uses flexible materials to stabilize the affected lumbar region while preserving the natural anatomy of the spine. The main objective of this research work is to investigate the stiffness variation of dynamic stabilization device under various loading conditions under compression, axial rotation and flexion. Three dimensional model of the two segment lumbar spine is developed using computed tomography (CT) scan images. The lumbar structure developed is analyzed in ANSYS workbench. Two types of dynamic stabilization are considered: one with stabilizing device as pedicle instrumentation and second with stabilization device inserted around the inter-vertebral disc. Analysis suggests that proper positioning of the dynamic stabilization device is of paramount significance prior to the surgery. Inserting the device in the posterior region indicates the adverse effects as it shows increase in the deformation of the inter-vertebral disc. Analysis executed by positioning stabilizing device around the inter-vertebral disc yields better result for various stiffness values under compression and other loadings. [Figure not available: see fulltext.

Geometrical aspects of patient-specific modelling of the intervertebral disc: collagen fibre orientation and residual stress distribution.

PubMed

Marini, Giacomo; Studer, Harald; Huber, Gerd; Püschel, Klaus; Ferguson, Stephen J

2016-06-01

Patient-specific modelling of the spine is a powerful tool to explore the prevention and the treatment of injuries and pathologies. Albeit several methods have been proposed for the discretization of the bony structures, the efficient representation of the intervertebral disc anisotropy remains a challenge, especially with complex geometries. Furthermore, the swelling of the disc's nucleus pulposus is normally added to the model after geometry definition, at the cost of changes of the material properties and an unrealistic description of the prestressed state. The aim of this study was to develop techniques, which preserve the patient-specific geometry of the disc and allow the representation of the system anisotropy and residual stresses, independent of the system discretization. Depending on the modelling features, the developed approaches resulted in a response of patient-specific models that was in good agreement with the physiological response observed in corresponding experiments. The proposed methods represent a first step towards the development of patient-specific models of the disc which respect both the geometry and the mechanical properties of the specific disc.

In Vitro Maturation and In Vivo Integration and Function of an Engineered Cell-Seeded Disc-like Angle Ply Structure (DAPS) for Total Disc Arthroplasty.

PubMed

Martin, J T; Gullbrand, S E; Kim, D H; Ikuta, K; Pfeifer, C G; Ashinsky, B G; Smith, L J; Elliott, D M; Smith, H E; Mauck, R L

2017-11-17

Total disc replacement with an engineered substitute is a promising avenue for treating advanced intervertebral disc disease. Toward this goal, we developed cell-seeded disc-like angle ply structures (DAPS) and showed through in vitro studies that these constructs mature to match native disc composition, structure, and function with long-term culture. We then evaluated DAPS performance in an in vivo rat model of total disc replacement; over 5 weeks in vivo, DAPS maintained their structure, prevented intervertebral bony fusion, and matched native disc mechanical function at physiologic loads in situ. However, DAPS rapidly lost proteoglycan post-implantation and did not integrate into adjacent vertebrae. To address this, we modified the design to include polymer endplates to interface the DAPS with adjacent vertebrae, and showed that this modification mitigated in vivo proteoglycan loss while maintaining mechanical function and promoting integration. Together, these data demonstrate that cell-seeded engineered discs can replicate many characteristics of the native disc and are a viable option for total disc arthroplasty.

Qualitative and quantitative assessment of collagen and elastin in annulus fibrosus of the physiologic and scoliotic intervertebral discs.

PubMed

Kobielarz, Magdalena; Szotek, Sylwia; Głowacki, Maciej; Dawidowicz, Joanna; Pezowicz, Celina

2016-09-01

The biophysical properties of the annulus fibrosus of the intervertebral disc are determined by collagen and elastin fibres. The progression of scoliosis is accompanied by a number of pathological changes concerning these structural proteins. This is a major cause of dysfunction of the intervertebral disc. The object of the study were annulus fibrosus samples excised from intervertebral discs of healthy subjects and patients treated surgically for scoliosis in the thoracolumbar or lumbar spine. The research material was subjected to structural analysis by light microscopy and quantitative analysis of the content of collagen types I, II, III and IV as well as elastin by immunoenzymatic test (ELISA). A statistical analysis was conducted to assess the impact of the sampling site (Mann-Whitney test, α=0.05) and scoliosis (Wilcoxon matched pairs test, α=0.05) on the obtained results. The microscopic studies conducted on scoliotic annulus fibrosus showed a significant architectural distortion of collagen and elastin fibres. Quantitative biochemical assays demonstrated region-dependent distribution of only collagen types I and II in the case of healthy intervertebral discs whereas in the case of scoliotic discs region-dependent distribution concerned all examined proteins of the extracellular matrix. Comparison of scoliotic and healthy annulus fibrosus revealed a significant decrease in the content of collagen type I and elastin as well as a slight increase in the proportion of collagen types III and IV. The content of collagen type II did not differ significantly between both groups. The observed anomalies are a manifestation of degenerative changes affecting annulus fibrosus of the intervertebral disc in patients suffering from scoliosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

The effects of flexion-distraction and drop techniques on disorders and Ferguson’s angle in female patients with lumbar intervertebral disc herniation

PubMed Central

Oh, Hyunju; Lee, Sangyong; Lee, Kwansub; Jeong, Mugeun

2018-01-01

[Purpose] This study examines the effects of the flexion-distraction technique and the drop technique on disorders and on Ferguson’s angle in female patients with lumbar intervertebral disc herniation. [Subjects and Methods] Thirty female patients with lumbar intervertebral disc herniation were divided into an experimental group (n=15) treated with flexion-distraction and drop techniques and a control group (n=15) treated with spinal decompression therapy. Both groups were treated three times a week over an eight-week period. [Results] In the comparison of changes within each group after treatment, both groups showed statistically significant decreases in disorders and in Ferguson’s angle. [Conclusion] Flexion-distraction and drop techniques may be an effective intervention to improve disorders and Ferguson’s angle in female patients with lumbar intervertebral disc herniation. PMID:29706701

[Influence of disc height on outcome of posterolateral fusion].

PubMed

Drain, O; Lenoir, T; Dauzac, C; Rillardon, L; Guigui, P

2008-09-01

Experimentally, posterolateral fusion only provides incomplete control of flexion-extension, rotation and lateral inclination forces. The stability deficit increases with increasing height of the anterior intervertebral space, which for some warrants the adjunction of an intersomatic arthrodesis in addition to the posterolateral graft. Few studies have been devoted to the impact of disc height on the outcome of posterolateral fusion. The purpose of this work was to investigate the spinal segment immobilized by the posterolateral fusion: height of the anterior intervertebral space, the clinical and radiographic impact of changes in disc height, and the short- and long-term impact of disc height measured preoperatively on clinical and radiographic outcome. In order to obtain a homogeneous group of patients, the series was limited to patients undergoing posterolateral arthrodesis for degenerative spondylolisthesis, in combination with radicular release. This was a retrospective analysis of a consecutive series of 66 patients with mean 52 months follow-up (range 3-63 months). A dedicated self-administered questionnaire was used to collect data on pre- and postoperative function, the SF-36 quality of life score, and patient satisfaction. Pre- and postoperative (early, one year, last follow-up) radiographic data were recorded: olisthesic level, disc height, intervertebral angle, intervertebral mobility (angular, anteroposterior), and global measures of sagittal balance (thoracic kyphosis, lumbar lordosis, T9 sagittal tilt, pelvic version, pelvic incidence, sacral slope). SpineView was used for all measures. Univariate analysis searched for correlations between variation in disc height and early postoperative function and quality of fusion at last follow-up. Multivariate analysis was applied to the following preoperative parameters: intervertebral angle, disc height, intervertebral mobility, sagittal balance parameters, use of osteosynthesis or not. At the olisthesic level, there was a 30% mean decrease in disc height and intervertebral angle. These variations were not correlated with functional outcome or quality of fusion observed at last follow-up. Disc height preoperatively did not affect these variations. The only factor correlated with decreased disc height was T9 sagittal tilt: disc height decreased more when T9 sagittal tilt approached 0 degrees . In this very restricted context (retrospective study, short arthrodesis for degenerative spondylolisthesis), we were unable to find any evidence supporting the notion that high disc height is an argument which should favor complementary intersomatic arthrodesis in combination with posterolateral fusion. Analysis of the spinal balance in the sagittal plane would probably allow a more pertinent assessment of the specific needs of individual patients.

[Effect of exercise load on apparent diffusion coefficient and fractional anisotropy of normal lumbar intervertebral discs in diffusion tensor imaging].

PubMed

Zhong, Xiu; Qiu, Shijun

2015-06-01

To investigate the effect of exercise load on apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of normal lumbar intervertebral discs in magnetic resonance (MR) diffusion tensor imaging (DTI). Thirty healthy volunteers (24 males and 6 females, aged 19 to 25 years) underwent examinations with MR T2WI and DTI of the lumbar intervertebral discs before and after exercise load. Pfirrmann grading was evaluated with T2WI, and the B0 map, ADC map and FA map were reconstructed based on the DTI data to investigate the changes in ADC and FA after exercise. Of the 30 volunteers (150 intervertebral discs) receiving the examination, 27 with discs of Pfirrminn grade II were included for analysis. In these 27 volunteers, the average ADC and FA before exercise were (1.99 ± 0.18)×10⁻³ mm²/s and 0.155∓0.059, respectively. After exercise, ADC was lowered significantly to (1.93 ± 0.17)×10⁻³ mm²/s (P<0.05) and FA increased slightly to 0.1623 ± 0.017 (P>0.05). DTI allows quantitatively analysis of the changes in water molecular diffusion and anisotropy of the lumbar intervertebral discs after exercise load, which can cause a decreased ADC and a increased FA value, and the change of ADC is more sensitive to exercise load.

Thoracolumbar Intervertebral Disc Area Morphometry in Elderly Chinese Men and Women: Radiographic Quantifications at Baseline and Changes at Year-4 Follow-up.

PubMed

Wáng, Jùn-Qīng; Káplár, Zoltán; Deng, Min; Griffith, James F; Leung, Jason C S; Kwok, Anthony W L; Kwok, Timothy; Leung, Ping Chung; Wáng, Yì Xiáng J

2018-05-15

A population-based radiographic study with longitudinal follow-up. To develop a quantitative index for lumbar disc space narrowing (DSN) evaluation in elderly subjects; to determine how DSN in the elderly is influenced by osteoporosis and sex. There is paucity of research on quantitative classification of lumbar DSN based on disc areal morphometry. With the database of Osteoporotic Fractures in Men (Hong Kong) and Osteoporotic Fractures in Women (Hong Kong) Studies and those who attended the year-4 follow-up (n = 1519 for men and n = 1546 for women), data of 491 women and 592 men were randomly selected. The anterior, middle, and posterior heights; anteroposterior diameter; and area of intervertebral discs (T4T5 to L4L5) were measured on lateral radiographs. Disc area index for lumbar spine (DAIL, disc area divided by the mean of the sum of square of the adjacent upper and lower vertebrae mid-height anterior-posterior diameter) was developed and compared with semiquantitative DSN expert grading. DAIL correlated with semiquantitative grading, with sensitivity and specificity varying from 87.3% to 96.8% for grade 1 DSN (<30% reduction in disc height), and 92.9% to 100% for grade 3 DSN (>60% reduction in disc height). The thoracolumbar disc area loss among men and women during 4-years' follow-up period varied between 1.32% and 3.56%, and it was greater for women (mean: 2.44%) than for men (mean: 1.90%, P = 0.044). Majority of lumbar DSN progressions during 72 to 76 years old were progression from normal disc space to grade 1 DSN. Osteoporosis was associated with greater disc area decrease, both for thoracic and lumbar discs. Lumbar DSN can be quantified using DAIL. In elderly Chinese, intervertebral disc narrowing over a 4-year period was greater in women than men, and associated with the presence of osteoporosis. 3.

[Effect of Basic Fibroblast Growth Factor and Transforming Growth Factor-Β1 Combined with Bone Marrow Mesenchymal Stem Cells on the Repair of Degenerated Intervertebral Discs in Rat Models].

PubMed

Jiang, Chao; Li, Da-peng; Zhang, Zhi-jian; Shu, Hao-ming; Hu, Lang; Li, Zheng-nan; Huang, Yong-hui

2015-08-01

To evaluate the effects of the combination of basic fibroblast growth factor (bFGF), transforming growth factor-Β1 (TGF-Β1), bone marrow mesenchymal stem cells (BMSCs), and temperature-responsive chitosan hydrogel (TCH) gel on the repair of degenerative intervertebral disc in rat models. Rat models of intervertebral disc degeneration were established by acupuncture. The degenerative effects were observed under magnetic resonance imaging (MRI). The BMSCs was cultured in vitro and then transfected by adenovirus with enhanced green fluorescent protein to make it carry the gene of enhanced green fluorescent protein,which functioned as fluorescence labeling. The SD rat models of intervertebral disc degeneration were divided into four groups: group A, treated with the combination of bFGF, TGF-Β1,BMSCs,and TCH gel; group B, treated with the combination of BMSCs and TCH gel;group C, treated with the combination of bFGF,TGF-Β1, and TCH gel;and group D, treated with PBS buffer solution. After the corresponding reagents were injected into the degenerative intervertebral discs of each group, the rats were cultivated for another four weeks and then the repair effects of the intervertebral discs were observed under MRI. Furthermore,the intervertebral discs of each group were taken out and observed by HE and Masson staining. The nucleus pulposus was aspirated and the expressions of aggrecan,collagen 2,Sox-9,and collagen I of nucleus pulposus of each group were tested by reverse transcription polymerase chain reaction and Western blot. The transplanted BMSCs survived in the intervertebral disc and differentiated into nucleus pulposus-like cells. MRI showed that:the signal intensity of the nucleus pulposus of group A was much higher than that of the rest groups, the signal intensity of group B was higher than that of group C, and the signal intensity of group D was the lowest,in which the dura mater spinalis was in compression and the spinal cord changed in beaded shape. The differences of the Pfirrmann grading among the four groups had statistical significance (P<0.05). The results of the HE and Masson stains showed:the intervertebral disc of group A was well-structured,the quantity of nucleus pulposus cells was larger than that of the other three groups,and the boundary between the nucleus pulposus and the annulus fibrosus was clearly defined;the quantity of the nucleus pulposus cells of group B was larger than that of group C, and the broken annulus fibrosus was not observed in group B, while the broken annulus fibrosus could be observed in group C; and, the nucleus pulposus cells of group D were replaced by fibrous tissue. The results of the reverse transcription polymerase chain reaction and Western blot tests showed that,in terms of the expressions of aggrecan,collagen 2 and Sox-9,group A was the highest, followed by group B,group C,and group D (P<0.05); in terms of the expression of collagen 1,there was no obvious difference among these four groups (P>0.05). The transplanted BMSCs can survive in the degenerative intervertebral disc and differentiate into nucleus pulposus-like cells. The combination of bFGF, TGF-Β1, BMSCs,and TCH gel has obvious repair effect on the degenerative intervertebral discs. The effect of the combination of BMSCs and TCH gel on transplantation therapy of the degenerative intervertebral discs is better than that of the combination of bFGF, TGF-Β1 and TCH gel but worse than that of the combination of bFGF, TGF-Β1, BMSCs, and TCH gel.

A Histopathological Scheme for the Quantitative Scoring of Intervertebral Disc Degeneration and the Therapeutic Utility of Adult Mesenchymal Stem Cells for Intervertebral Disc Regeneration

PubMed Central

Shu, Cindy C.; Smith, Margaret M.; Smith, Susan M.; Dart, Andrew J.; Little, Christopher B.; Melrose, James

2017-01-01

The purpose of this study was to develop a quantitative histopathological scoring scheme to evaluate disc degeneration and regeneration using an ovine annular lesion model of experimental disc degeneration. Toluidine blue and Haematoxylin and Eosin (H&E) staining were used to evaluate cellular morphology: (i) disc structure/lesion morphology; (ii) proteoglycan depletion; (iii) cellular morphology; (iv) blood vessel in-growth; (v) cell influx into lesion; and (vi) cystic degeneration/chondroid metaplasia. Three study groups were examined: 5 × 5 mm lesion; 6 × 20 mm lesion; and 6 × 20 mm lesion plus mesenchymal stem cell (MSC) treatment. Lumbar intervertebral discs (IVDs) were scored under categories (i–vi) to provide a cumulative score, which underwent statistical analysis using STATA software. Focal proteoglycan depletion was associated with 5 × 5 mm annular rim lesions, bifurcations, annular delamellation, concentric and radial annular tears and an early influx of blood vessels and cells around remodeling lesions but the inner lesion did not heal. Similar features in 6 × 20 mm lesions occurred over a 3–6-month post operative period. MSCs induced a strong recovery in discal pathology with a reduction in cumulative histopathology degeneracy score from 15.2 to 2.7 (p = 0.001) over a three-month recovery period but no recovery in carrier injected discs. PMID:28498326

A Histopathological Scheme for the Quantitative Scoring of Intervertebral Disc Degeneration and the Therapeutic Utility of Adult Mesenchymal Stem Cells for Intervertebral Disc Regeneration.

PubMed

Shu, Cindy C; Smith, Margaret M; Smith, Susan M; Dart, Andrew J; Little, Christopher B; Melrose, James

2017-05-12

The purpose of this study was to develop a quantitative histopathological scoring scheme to evaluate disc degeneration and regeneration using an ovine annular lesion model of experimental disc degeneration. Toluidine blue and Haematoxylin and Eosin (H&E) staining were used to evaluate cellular morphology: (i) disc structure/lesion morphology; (ii) proteoglycan depletion; (iii) cellular morphology; (iv) blood vessel in-growth; (v) cell influx into lesion; and (vi) cystic degeneration/chondroid metaplasia. Three study groups were examined: 5 × 5 mm lesion; 6 × 20 mm lesion; and 6 × 20 mm lesion plus mesenchymal stem cell (MSC) treatment. Lumbar intervertebral discs (IVDs) were scored under categories (i-vi) to provide a cumulative score, which underwent statistical analysis using STATA software. Focal proteoglycan depletion was associated with 5 × 5 mm annular rim lesions, bifurcations, annular delamellation, concentric and radial annular tears and an early influx of blood vessels and cells around remodeling lesions but the inner lesion did not heal. Similar features in 6 × 20 mm lesions occurred over a 3-6-month post operative period. MSCs induced a strong recovery in discal pathology with a reduction in cumulative histopathology degeneracy score from 15.2 to 2.7 ( p = 0.001) over a three-month recovery period but no recovery in carrier injected discs.

Impaired intervertebral disc development and premature disc degeneration in mice with notochord-specific deletion of CCN2.

PubMed

Bedore, Jake; Sha, Wei; McCann, Matthew R; Liu, Shangxi; Leask, Andrew; Séguin, Cheryle A

2013-10-01

Currently, our ability to treat intervertebral disc (IVD) degeneration is hampered by an incomplete understanding of disc development and aging. The specific function of matricellular proteins, including CCN2, during these processes remains an enigma. The aim of this study was to determine the tissue-specific localization of CCN proteins and to characterize their role in IVD tissues during embryonic development and age-related degeneration by using a mouse model of notochord-specific CCN2 deletion. Expression of CCN proteins was assessed in IVD tissues from wild-type mice beginning on embryonic day 15.5 to 17 months of age. Given the enrichment of CCN2 in notochord-derived tissues, we generated notochord-specific CCN2-null mice to assess the impact on the IVD structure and extracellular matrix composition. Using a combination of histologic evaluation and magnetic resonance imaging (MRI), IVD health was assessed. Loss of the CCN2 gene in notochord-derived cells disrupted the formation of IVDs in embryonic and newborn mice, resulting in decreased levels of aggrecan and type II collagen and concomitantly increased levels of type I collagen within the nucleus pulposus. CCN2-knockout mice also had altered expression of CCN1 (Cyr61) and CCN3 (Nov). Mirroring its role during early development, notochord-specific CCN2 deletion accelerated age-associated degeneration of IVDs. Using a notochord-specific gene targeting strategy, this study demonstrates that CCN2 expression by nucleus pulposus cells is essential to the regulation of IVD development and age-associated tissue maintenance. The ability of CCN2 to regulate the composition of the intervertebral disc suggests that it may represent an intriguing clinical target for the treatment of disc degeneration. Copyright © 2013 by the American College of Rheumatology.

The collagen structure of bovine intervertebral disc studied using polarization-sensitive optical coherence tomography

NASA Astrophysics Data System (ADS)

Matcher, Stephen J.; Winlove, C. Peter; Gangnus, Sergei V.

2004-04-01

Polarization-sensitive optical coherence tomography (PS-OCT) is used to measure the birefringence properties of bovine intervertebral disc and equine flexor tendon. For equine tendon the birefringence Dgrn is (6.0 ± 0.2) × 10-3 at a wavelength of 1.3 µm. This is somewhat larger than the values reported for bovine tendon. The surface region of the annulus fibrosus of a freshly excised intact bovine intervertebral disc displays an identical value of birefringence, Dgrn = (6.0 ± 0.6) × 10-3 at 1.3 µm. The nucleus pulposus does not display birefringence, the measured apparent value of Dgrn = (0.39 ± 0.01) × 10-3 being indistinguishable from the effects of depolarization due to multiple scattering. A clear difference is found between the depth-resolved retardance of equine tendon and that of bovine intervertebral disc. This apparently relates to the lamellar structure of the latter tissue, in which the collagen fibre orientation alternates between successive lamellae. A semi-empirical model based on Jones calculus shows that the measurements are in reasonable agreement with previous optical and x-ray data. These results imply that PS-OCT could be a useful tool to study collagen organization within the intervertebral disc in vitro and possibly in vivo and its variation with applied load and disease.

Fluid flow and convective transport of solutes within the intervertebral disc.

PubMed

Ferguson, Stephen J; Ito, Keita; Nolte, Lutz P

2004-02-01

Previous experimental and analytical studies of solute transport in the intervertebral disc have demonstrated that for small molecules diffusive transport alone fulfils the nutritional needs of disc cells. It has been often suggested that fluid flow into and within the disc may enhance the transport of larger molecules. The goal of the study was to predict the influence of load-induced interstitial fluid flow on mass transport in the intervertebral disc. An iterative procedure was used to predict the convective transport of physiologically relevant molecules within the disc. An axisymmetric, poroelastic finite-element structural model of the disc was developed. The diurnal loading was divided into discrete time steps. At each time step, the fluid flow within the disc due to compression or swelling was calculated. A sequentially coupled diffusion/convection model was then employed to calculate solute transport, with a constant concentration of solute being provided at the vascularised endplates and outer annulus. Loading was simulated for a complete diurnal cycle, and the relative convective and diffusive transport was compared for solutes with molecular weights ranging from 400 Da to 40 kDa. Consistent with previous studies, fluid flow did not enhance the transport of low-weight solutes. During swelling, interstitial fluid flow increased the unidirectional penetration of large solutes by approximately 100%. Due to the bi-directional temporal nature of disc loading, however, the net effect of convective transport over a full diurnal cycle was more limited (30% increase). Further study is required to determine the significance of large solutes and the timing of their delivery for disc physiology.

Lamellar and fibre bundle mechanics of the annulus fibrosus in bovine intervertebral disc.

PubMed

Vergari, Claudio; Mansfield, Jessica; Meakin, Judith R; Winlove, Peter C

2016-06-01

The intervertebral disc is a multicomposite structure, with an outer fibrous ring, the annulus fibrosus, retaining a gel-like core, the nucleus pulposus. The disc presents complex mechanical behaviour, and it is of high importance for spine biomechanics. Advances in multiscale modelling and disc repair raised a need for new quantitative data on the finest details of annulus fibrosus mechanics. In this work we explored inter-lamella and inter-bundle behaviour of the outer annulus using micromechanical testing and second harmonic generation microscopy. Twenty-one intervertebral discs were dissected from cow tails; the nucleus and inner annulus were excised to leave a ring of outer annulus, which was tested in circumferential loading while imaging the tissue's collagen fibres network with sub-micron resolution. Custom software was developed to determine local tissue strains through image analysis. Inter-bundle linear and shear strains were 5.5 and 2.8 times higher than intra-bundle strains. Bundles tended to remain parallel while rotating under loading, with large slipping between them. Inter-lamella linear strain was almost 3 times the intra-lamella one, but no slipping was observed at the junction between lamellae. This study confirms that outer annulus straining is mainly due to bundles slipping and rotating. Further development of disc multiscale modelling and repair techniques should take into account this modular behaviour of the lamella, rather than considering it as a homogeneous fibre-reinforced matrix. The intervertebral disc is an organ tucked between each couple of vertebrae in the spine. It is composed by an outer fibrous layer retaining a gel-like core. This organ undergoes severe and repeated loading during everyday life activities, since it is the compliant component that gives the spine its flexibility. Its properties are affected by pathologies such as disc degeneration, a major cause of back pain. In this article we explored the micromechanical behaviour of the disc's outer layer using second harmonic generation, a technique which allowed us to visualize, with unprecedented detail, how bundles of collagen fibres slide relative to each other when loaded. Our results will help further the development of new multiscale numerical models and repairing techniques. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Biological intervertebral disc replacement: an in vivo model and comparison of two surgical techniques to approach the rat caudal disc

PubMed Central

Gebhard, Harry; James, Andrew R.; Bowles, Robby D.; Dyke, Jonathan P.; Saleh, Tatianna; Doty, Stephen P.; Bonassar, Lawrence J.; Härtl, Roger

2011-01-01

Study design: Prospective randomized animal study. Objective: To determine a surgical technique for reproducible and functional intervertebral disc replacement in an orthotopic animal model. Methods: The caudal 3/4 intervertebral disc (IVD) of the rat tail was approached by two surgical techniques: blunt dissection, stripping and retracting (Technique 1) or incising and repairing (Technique 2) the dorsal longitudinal tendons. The intervertebral disc was dissected and removed, and then either discarded or reinserted. Outcome measures were perioperative complications, spontaneous tail movement, 7T MRI (T1- and T2-sequences for measurement of disc space height (DSH) and disc hydration). Microcomputed tomographic imaging (micro CT) was additionally performed postmortem. Results: No vascular injuries occurred and no systemic or local infections were observed over the course of 1 month. Tail movements were maintained. With tendon retraction (Technique 1) gross loss of DSH occurred with both discectomy and reinsertion. Tendon division (Technique 2) maintained DSH with IVD reinsertion but not without. The DSH was demonstrated on MRI measurement. A new scoring system to assess IVD appearances was described. Conclusions: The rat tail model, with a tendon dividing surgical technique, can function as an orthotopic animal model for IVD research. Mechanical stimulation is maintained by preserved tail movements. 7T MRI is a feasible modality for longitudinal monitoring for the rat caudal disc. PMID:22956934

Combined Therapies of Modified Taiyi Miraculous Moxa Roll and Cupping for Patients with Lumbar Intervertebral Disc Herniation

PubMed Central

Dong, Dayong; Xue, Jinbiao; Zheng, Xiaoting

2018-01-01

Lumbar intervertebral disc herniation is a kind of syndrome caused by stimulation or pressure of nerve root and cauda equina due to intervertebral disc disorder, fibrous ring rupture, and pulpiform nucleus protrusion. Application of traditional Chinese medicine (TCM) including acupuncture therapy and cupping therapy is unique and effective treatment for lumbar intervertebral disc herniation in China. Hence, we try to investigate the combined clinical efficacy of modified Taiyi miraculous moxa roll and cupping therapy on patients with lumbar intervertebral disc herniation. Seventy patients were randomly assigned into combined treatment group (n = 35) and control group (n = 35). The treatment group received combined therapy of modified Taiyi miraculous moxa roll and cupping therapy, while control group received acupuncture therapy alone. Diagnostic criteria of TCM syndrome, Japanese Orthopedic Association (JOA) score, and simplified McGill pain questionnaire (MPQ) were used to evaluate the therapy. 11 and 13 out of 35 subjects in the combined treatment group had improvement > 75% and between 50% and 75%, respectively. The corresponding number was 2 and 22 of 35 subjects in the acupuncture group. There was significant difference in the clinical efficacy between the treatment group and control group (P = 0.036). The scores of JOA and MPQ detected in the patients of the two groups (P < 0.05) also showed statistically significant differences. Moreover, no serious adverse events occurred in the patients, who received cupping therapy or acupuncture. The combined or alone therapies can effectively improve the treatment efficacy in the patients with lumbar intervertebral disc herniation, while the combined therapies show more comparative effectiveness. Furthermore, the combined therapies are potentially safe and cost-effective and also benefit the improvement of short-term pain. Therefore, the combined therapies of the two ancient TCM deserve further clinical applications. PMID:29785195

Combined Therapies of Modified Taiyi Miraculous Moxa Roll and Cupping for Patients with Lumbar Intervertebral Disc Herniation.

PubMed

Cai, Chunyue; Gong, Yuefeng; Dong, Dayong; Xue, Jinbiao; Zheng, Xiaoting; Zhong, Zhangfeng; Shao, Jialong; Mi, Daguo

2018-01-01

Lumbar intervertebral disc herniation is a kind of syndrome caused by stimulation or pressure of nerve root and cauda equina due to intervertebral disc disorder, fibrous ring rupture, and pulpiform nucleus protrusion. Application of traditional Chinese medicine (TCM) including acupuncture therapy and cupping therapy is unique and effective treatment for lumbar intervertebral disc herniation in China. Hence, we try to investigate the combined clinical efficacy of modified Taiyi miraculous moxa roll and cupping therapy on patients with lumbar intervertebral disc herniation. Seventy patients were randomly assigned into combined treatment group ( n = 35) and control group ( n = 35). The treatment group received combined therapy of modified Taiyi miraculous moxa roll and cupping therapy, while control group received acupuncture therapy alone. Diagnostic criteria of TCM syndrome, Japanese Orthopedic Association (JOA) score, and simplified McGill pain questionnaire (MPQ) were used to evaluate the therapy. 11 and 13 out of 35 subjects in the combined treatment group had improvement > 75% and between 50% and 75%, respectively. The corresponding number was 2 and 22 of 35 subjects in the acupuncture group. There was significant difference in the clinical efficacy between the treatment group and control group ( P = 0.036). The scores of JOA and MPQ detected in the patients of the two groups ( P < 0.05) also showed statistically significant differences. Moreover, no serious adverse events occurred in the patients, who received cupping therapy or acupuncture. The combined or alone therapies can effectively improve the treatment efficacy in the patients with lumbar intervertebral disc herniation, while the combined therapies show more comparative effectiveness. Furthermore, the combined therapies are potentially safe and cost-effective and also benefit the improvement of short-term pain. Therefore, the combined therapies of the two ancient TCM deserve further clinical applications.

The potential of chondrogenic pre-differentiation of adipose-derived mesenchymal stem cells for regeneration in harsh nucleus pulposus microenvironment.

PubMed

Wang, Jingkai; Tao, Yiqing; Zhou, Xiaopeng; Li, Hao; Liang, Chengzhen; Li, Fangcai; Chen, Qi-Xin

2016-12-01

Recent studies indicated that cell-based therapy could be a promising approach to treat intervertebral disc degeneration. Though the harsh microenvironment in disc is still challenging to implanted cells, it could be overcome by pre-conditioning graft cells before transplantation, suggested by previous literatures. Therefore, we designed this study to identify the potential effect of chondrogenic pre-differentiation on adipose-derived mesenchymal stem cells in intervertebral disc-like microenvironment, characterized by limited nutrition, acidic, and high osmosis in vitro. Adipose-derived mesenchymal stem cells of rat were divided into five groups, embedded in type II collagen scaffold, and cultured in chondrogenic differentiation medium for 0, 3, 7, 10, and 14 days. Then, the adipose-derived mesenchymal stem cells were implanted and cultured in intervertebral disc-like condition. The proliferation and differentiation of adipose-derived mesenchymal stem cells were evaluated by cell counting kit-8 test, real-time quantitative polymerase chain reaction, and Western blotting and immunofluorescence analysis. Analyzed by the first week in intervertebral disc-like condition, the results showed relatively greater proliferative capability and extracellular matrix synthesis ability of the adipose-derived mesenchymal stem cells pre-differentiated for 7 and 10 days than the control. We concluded that pre-differentiation of rat adipose-derived mesenchymal stem cells in chondrogenic culture medium for 7 to 10 days could promote the regeneration effect of adipose-derived mesenchymal stem cells in intervertebral disc-like condition, and the pre-differentiated cells could be a promising cell source for disc regeneration medicine.

Comparison of the intervertebral disc spaces between axial and anterior lean cervical traction.

PubMed

Chung, Chin-Teng; Tsai, Sen-Wei; Chen, Chun-Jung; Wu, Ting-Chung; Wang, David; Lan, Haw-Chang H; Wu, Shyi-Kuen

2009-11-01

The insufficient investigations on the changes of spinal structures during traction prevent further exploring the possible therapeutic mechanism of cervical traction. A blind randomized crossover-design study was conducted to quantitatively compare the intervertebral disc spaces between axial and anterior lean cervical traction in sitting position. A total of 96 radiographic images from the baseline measurements, axial and anterior lean tractions in 32 asymptomatic subjects were digitized for further analysis. The intra- and inter-examiner reliabilities for measuring the intervertebral disc spaces were in good ranges (ICCs = 0.928-0.942). With the application of anterior lean traction, the statistical increases were detected both in anterior and in posterior disc spaces compared to the baseline (0.29 mm and 0.24 mm; both P < 0.01) and axial traction (0.16 mm and 0.35 mm; both P < 0.01). The greater intervertebral disc spaces obtained during anterior lean traction might be associated with the more even distribution of traction forces over the anterior and posterior neck structures. The neck extension moment through mandible that generally occurred in the axial traction could be counteracted by the downward force of head weight during anterior lean traction. This study quantitatively demonstrated that anterior lean traction in sitting position provided more intervertebral disc space enlargements in both anterior and posterior aspects than axial traction did. These findings may serve as a therapeutic reference when cervical traction is suggested.

[Principles of intervertebral disc assessment in private accident insurance].

PubMed

Steinmetz, M; Dittrich, V; Röser, K

2015-09-01

Due to the spread of intervertebral disc degeneration, insurance companies and experts are regularly confronted with related assessments of insured persons under their private accident insurance. These claims pose a particular challenge for experts, since, in addition to the clinical assessment of the facts, extensive knowledge of general accident insurance conditions, case law and current study findings is required. Each case can only be properly assessed through simultaneous consideration of both the medical and legal facts. These guidelines serve as the basis for experts and claims.managers with respect to the appropriate individual factual assessment of intervertebral disc degeneration in private accident insurance.

In vivo dynamic stiffness of the porcine lumbar spine exposed to cyclic loading: influence of load and degeneration.

PubMed

Kaigle, A; Ekström, L; Holm, S; Rostedt, M; Hansson, T

1998-02-01

The dynamic axial stiffness of the L2-3 motion segment subjected to vibratory loading under intact and injured states of the intervertebral disc was studied using an in vivo porcine model. Three groups of animals with the following states of the intervertebral discs were studied: intact disc, acutely injured disc, and degenerated disc. A miniaturized servo-hydraulic exciter was used to sinusoidally vibrate the motion segment from 0.05 to 25 Hz under a compressive load with a peak value of either 100 or 200 N. The dynamic axial stiffness of the intervertebral disc was calculated at 1-Hz intervals over the frequency range. The results showed that the dynamic axial stiffness was frequency dependent. A positive relationship was found between an increase in mean dynamic stiffness and load magnitude. An increase in mean stiffness with successive exposures at the same load magnitude was observed, despite the allowance of a recovery period between loading. The greatest difference was noted between the first and second load sets. No significant change in stiffness was found due to an acute disc injury, whereas a significant increase in mean stiffness was found for the degenerated disc group as compared with the intact group. The form of the frequency response curve, however, remained relatively unaltered regardless of the degenerated state of the disc. With heavier loads, repeated loading, and/or disc degeneration, the stiffness of the intervertebral disc increases. An increase in stiffness can mean a reduction in the amount of allowable motion within the motion segment or a potentially harmful increase in force to obtain the desired motion. This may locally result in greater stresses due to an altered ability of the disc to distribute loads.

Translation of an Engineered Nanofibrous Disc-like Angle Ply Structure for Intervertebral Disc Replacement in a Small Animal Model

PubMed Central

Martin, John T.; Milby, Andrew H.; Chiaro, Joseph A.; Kim, Dong Hwa; Hebela, Nader M.; Smith, Lachlan J.; Elliott, Dawn M.; Mauck, Robert L.

2015-01-01

Intervertebral disc degeneration has been implicated in the etiology of low back pain; however the current surgical strategies for treating symptomatic disc disease are limited. A variety of materials have been developed to replace disc components, including the nucleus pulposus (NP), the annulus fibrosus (AF), and their combination into disc-like engineered constructs. We have previously shown that layers of electrospun poly(ε-caprolactone) scaffold, mimicking the hierarchical organization of the native AF, have functional parity with native tissue. Likewise, we have combined these structures with cell-seeded hydrogels (as an NP replacement) to form disc-like angle ply structures (DAPS). The objective of this study was to develop a model for the evaluation of DAPS in vivo. Through a series of studies, we developed a surgical approach to replace the rat caudal disc with an acellular DAPS and then stabilize the motion segment by external fixation. We then optimized cell infiltration into DAPS by including sacrificial poly(ethylene oxide) layers interspersed throughout the angle-ply structure. Our findings illustrate that DAPS are stable in the caudal spine, are infiltrated by cells from the peri-implant space, and that infiltration is expedited by providing additional routes for cell migration. These findings establish a new in vivo platform in which to evaluate and optimize the design of functional disc replacements. PMID:24560621

Quantitative in vivo MRI evaluation of lumbar facet joints and intervertebral discs using axial T2 mapping.

PubMed

Stelzeneder, David; Messner, Alina; Vlychou, Marianna; Welsch, Goetz H; Scheurecker, Georg; Goed, Sabine; Pieber, Karin; Pflueger, Verena; Friedrich, Klaus M; Trattnig, Siegfried

2011-11-01

To assess the feasibility of T2 mapping of lumbar facet joints and intervertebral discs in a single imaging slab and to compare the findings with morphological grading. Sixty lumbar spine segments from 10 low back pain patients and 5 healthy volunteers were examined by axial T2 mapping and morphological MRI at 3.0 Tesla. Regions of interest were drawn on a single slice for the facet joints and the intervertebral discs (nucleus pulposus, anterior and posterior annulus fibrosus). The Weishaupt grading was used for facet joints and the Pfirrmann score was used for morphological disc grading ("normal" vs. "abnormal" discs). The inter-rater agreement was excellent for the facet joint T2 evaluation (r = 0.85), but poor for the morphological Weishaupt grading (kappa = 0.15). The preliminary results show similar facet joint T2 values in segments with normal and abnormal Pfirrmann scores. There was no difference in mean T2 values between facet joints in different Weishaupt grading groups. Facet joint T2 values showed a weak correlation with T2 values of the posterior annulus (r = 0.32) This study demonstrates the feasibility of a combined T2 mapping approach for the facet joints and intervertebral discs using a single axial slab.

Hygroviscoelasticity of the Human Intervertebral Disc.

DTIC Science & Technology

1980-07-01

the intervertebral disc (Figures 2(a) and 2(b)). -7- 7 CERVICAL CURVE (C1 -C7 (CERVICAL LORDOSIS CURVE) THORACIC CURVE (T I- T12) $ (DORSAL KYPHOSIS...CURVE) LUMBAR CURVE (L 1-1.5 ) (LUMBAR LORDOSIS CURVE) PELVIC CURVE (SACRUM) COCCYX FIGURE 1 Lateral View of Vertebral Column *1 -8- POSTERIOR

Expression of growth differentiation factor 6 in the human developing fetal spine retreats from vertebral ossifying regions and is restricted to cartilaginous tissues.

PubMed

Wei, Aiqun; Shen, Bojiang; Williams, Lisa A; Bhargav, Divya; Gulati, Twishi; Fang, Zhimin; Pathmanandavel, Sarennya; Diwan, Ashish D

2016-02-01

During embryogenesis vertebral segmentation is initiated by sclerotomal cell migration and condensation around the notochord, forming anlagen of vertebral bodies and intervertebral discs. The factors that govern the segmentation are not clear. Previous research demonstrated that mutations in growth differentiation factor 6 resulted in congenital vertebral fusion, suggesting this factor plays a role in development of vertebral column. In this study, we detected expression and localization of growth differentiation factor 6 in human fetal spinal column, especially in the period of early ossification of vertebrae and the developing intervertebral discs. The extracellular matrix proteins were also examined. Results showed that high levels of growth differentiation factor 6 were expressed in the nucleus pulposus of intervertebral discs and the hypertrophic chondrocytes adjacent to the ossification centre in vertebral bodies, where strong expression of proteoglycan and collagens was also detected. As fetal age increased, the expression of growth differentiation factor 6 was decreased correspondingly with the progress of ossification in vertebral bodies and restricted to cartilaginous regions. This expression pattern and the genetic link to vertebral fusion suggest that growth differentiation factor 6 may play an important role in suppression of ossification to ensure proper vertebral segmentation during spinal development. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Level of Education as a Risk Factor for Extensive Prevalence of Cervical Intervertebral Disc Degenerative Changes and Chronic Neck Pain.

PubMed

Markotić, Vedran; Zubac, Damir; Miljko, Miro; Šimić, Goran; Zalihić, Amra; Bogdan, Gojko; Radančević, Dorijan; Šimić, Ana Dugandžić; Mašković, Josip

2017-09-01

The aim of this study was to document the prevalence of degenerative intervertebral disc changes in the patients who previously reported symptoms of neck pain and to determine the influence of education level on degenerative intervertebral disc changes and subsequent chronic neck pain. One hundred and twelve patients were randomly selected from the University Hospital in Mostar, Bosna and Herzegovina, (aged 48.5±12.7 years) and submitted to magnetic resonance imaging (MRI) of the cervical spine. MRI of 3.0 T (Siemens, Skyrim, Erlangen, Germany) was used to obtain cervical spine images. Patients were separated into two groups based on their education level: low education level (LLE) and high education level (HLE). Pfirrmann classification was used to document intervertebral disc degeneration, while self-reported chronic neck pain was evaluated using the previously validated Oswestry questionnaire. The entire logistic regression model containing all predictors was statistically significant, (χ 2 (3)=12.2, p=0.02), and was able to distinguish between respondents who had chronic neck pain and vice versa. The model explained between 10.0% (Cox-Snell R 2 ) and 13.8% (Nagelkerke R 2 ) of common variance with Pfirrmann classification, and it had the strength to discriminate and correctly classify 69.6% of patients. The probability of a patient being classified in the high or low group of degenerative disc changes according to the Pfirrmann scale was associated with the education level (Wald test: 5.5, p=0.02). Based on the Pfirrmann assessment scale, the HLE group was significantly different from the LLE group in the degree of degenerative changes of the cervical intervertebral discs (U=1,077.5, p=0.001). A moderate level of intervertebral disc degenerative changes (grade II and III) was equally matched among all patients, while the overall results suggest a higher level of education as a risk factor leading to cervical disc degenerative changes, regardless of age differences among respondents. Copyright© by the National Institute of Public Health, Prague 2017

Degenerative spinal disease in large felids.

PubMed

Kolmstetter, C; Munson, L; Ramsay, E C

2000-03-01

Degenerative spinal disorders, including intervertebral disc disease and spondylosis, seldom occur in domestic cats. In contrast, a retrospective study of 13 lions (Panthera leo), 16 tigers (Panthera tigris), 4 leopards (Panthera pardis), 1 snow leopard (Panthera uncia), and 3 jaguars (Panthera onca) from the Knoxville Zoo that died or were euthanatized from 1976 to 1996 indicated that degenerative spinal disease is an important problem in large nondomestic felids. The medical record, radiographic data, and the necropsy report of each animal were examined for evidence of intervertebral disc disease or spondylosis. Eight (three lions, four tigers, and one leopard) animals were diagnosed with degenerative spinal disease. Clinical signs included progressively decreased activity, moderate to severe rear limb muscle atrophy, chronic intermittent rear limb paresis, and ataxia. The age at onset of clinical signs was 10-19 yr (median = 18 yr). Radiographic evaluation of the spinal column was useful in assessing the severity of spinal lesions, and results were correlated with necropsy findings. Lesions were frequently multifocal, included intervertebral disc mineralization or herniation with collapsed intervertebral disc spaces, and were most common in the lumbar area but also involved cervical and thoracic vertebrae. Marked spondylosis was present in the cats with intervertebral disc disease, presumably subsequent to vertebral instability. Six of the animals' spinal cords were examined histologically, and five had acute or chronic damage to the spinal cord secondary to disc protrusion. Spinal disease should be suspected in geriatric large felids with decreased appetite or activity. Radiographic evaluation of the spinal column is the most useful method to assess the type and severity of spinal lesions.

New Challenges for Intervertebral Disc Treatment Using Regenerative Medicine

PubMed Central

Masuda, Koichi

2010-01-01

The development of tissue engineering therapies for the intervertebral disc is challenging due to ambiguities of disease and pain mechanisms in patients, and lack of consensus on preclinical models for safety and efficacy testing. Although the issues associated with model selection for studying orthopedic diseases or treatments have been discussed often, the multifaceted challenges associated with developing intervertebral disc tissue engineering therapies require special discussion. This review covers topics relevant to the clinical translation of tissue-engineered technologies: (1) the unmet clinical need, (2) appropriate models for safety and efficacy testing, (3) the need for standardized model systems, and (4) the translational pathways leading to a clinical trial. For preclinical evaluation of new therapies, we recommend establishing biologic plausibility of efficacy and safety using models of increasing complexity, starting with cell culture, small animals (rats and rabbits), and then large animals (goat and minipig) that more closely mimic nutritional, biomechanical, and surgical realities of human application. The use of standardized and reproducible experimental procedures and outcome measures is critical for judging relative efficacy. Finally, success will hinge on carefully designed clinical trials with well-defined patient selection criteria, gold-standard controls, and objective outcome metrics to assess performance in the early postoperative period. PMID:19903086

Effect of Survivin gene therapy via lentivirus vector on the course of intervertebral disc degeneration in an in vivo rabbit model.

PubMed

Yue, Bin; Lin, Yazhou; Ma, Xuexiao; Zhang, Guoqing; Chen, Bohua

2016-11-01

The aim of the current study was to use gene therapy to attenuate or reverse the degenerative process within the intervertabral disc. The effect of survivin gene therapy via lentiviral vector transfection on the course of intervertebral disc degeneration was investigated in the current study in an in vivo rabbit model. A total of 15 skeletally mature female New Zealand White rabbits were randomly divided into three groups: Punctured blank control group (group A, n=5), punctured empty vector control group (group B, n=5) and the treatment group (group C, n=5). Computed tomography‑guided puncture was performed at the L3‑L4 and L4‑L5 discs, in accordance with a previously validated rabbit annulotomy model for intervertebral disc degeneration. After 3 weeks, a lentiviral vector (LV) carrying survivin was injected into the nucleus pulposus. The results demonstrated that through magnetic resonance imaging, histology, gene expression, protein content and apoptosis analyses, group A and B were observed to exhibit disc degeneration, which increased over time, and no significant difference was observed between the two groups (P>0.05). However, there was reduced disc degeneration in group C compared with the punctured control groups, and the difference was statistically significant (P<0.05). Overall, the results of the present study demonstrated that injection of the LV carrying survivin into punctured rabbit intervertebral discs acted to delay changes associated with the degeneration of the discs. Although data from animal models should be extrapolated to the human condition with caution, the present study suggests potential for the use of gene therapy to decelerate disc degeneration.

Formation, function, and exhaustion of notochordal cytoplasmic vacuoles within intervertebral disc: current understanding and speculation.

PubMed

Wang, Feng; Gao, Zeng-Xin; Cai, Feng; Sinkemani, Arjun; Xie, Zhi-Yang; Shi, Rui; Wei, Ji-Nan; Wu, Xiao-Tao

2017-08-22

Notochord nucleus pulposus cells are characteristic of containing abundant and giant cytoplasmic vacuoles. This review explores the embryonic formation, biological function, and postnatal exhaustion of notochord vacuoles, aiming to characterize the signal network transforming the vacuolated nucleus pulposus cells into the vacuole-less chondrocytic cells. Embryonically, the cytoplasmic vacuoles within vertebrate notochord originate from an evolutionarily conserved vacuolation process during neurulation, which may continue to provide mechanical and signal support in constructing a mammalian intervertebral disc. For full vacuolation, a vacuolating specification from dorsal organizer cells, synchronized convergent extension, well-structured notochord sheath, and sufficient post-Golgi trafficking in notochord cells are required. Postnatally, age-related and species-specific exhaustion of vacuolated nucleus pulposus cells could be potentiated by Fas- and Fas ligand-induced apoptosis, intolerance to mechanical stress and nutrient deficiency, vacuole-mediated proliferation check, and gradual de-vacuolation within the avascular and compression-loaded intervertebral disc. These results suggest that the notochord vacuoles are active and versatile organelles for both embryonic notochord and postnatal nucleus pulposus, and may provide novel information on intervertebral disc degeneration to guide cell-based regeneration.

Formation, function, and exhaustion of notochordal cytoplasmic vacuoles within intervertebral disc: current understanding and speculation

PubMed Central

Sinkemani, Arjun; Xie, Zhi-Yang; Shi, Rui; Wei, Ji-Nan; Wu, Xiao-Tao

2017-01-01

Notochord nucleus pulposus cells are characteristic of containing abundant and giant cytoplasmic vacuoles. This review explores the embryonic formation, biological function, and postnatal exhaustion of notochord vacuoles, aiming to characterize the signal network transforming the vacuolated nucleus pulposus cells into the vacuole-less chondrocytic cells. Embryonically, the cytoplasmic vacuoles within vertebrate notochord originate from an evolutionarily conserved vacuolation process during neurulation, which may continue to provide mechanical and signal support in constructing a mammalian intervertebral disc. For full vacuolation, a vacuolating specification from dorsal organizer cells, synchronized convergent extension, well-structured notochord sheath, and sufficient post-Golgi trafficking in notochord cells are required. Postnatally, age-related and species-specific exhaustion of vacuolated nucleus pulposus cells could be potentiated by Fas- and Fas ligand-induced apoptosis, intolerance to mechanical stress and nutrient deficiency, vacuole-mediated proliferation check, and gradual de-vacuolation within the avascular and compression-loaded intervertebral disc. These results suggest that the notochord vacuoles are active and versatile organelles for both embryonic notochord and postnatal nucleus pulposus, and may provide novel information on intervertebral disc degeneration to guide cell-based regeneration. PMID:28915712

Intervertebral disc regeneration or repair with biomaterials and stem cell therapy--feasible or fiction?

PubMed

Chan, Samantha C W; Gantenbein-Ritter, Benjamin

2012-05-31

The "gold standard" for treatment of intervertebral disc herniations and degenerated discs is still spinal fusion, corresponding to the saying "no disc - no pain". Mechanical prostheses, which are currently implanted, do only have medium outcome success and have relatively high re-operation rates. Here, we discuss some of the biological intervertebral disc replacement approaches, which can be subdivided into at least two classes in accordance to the two different tissue types, the nucleus pulposus (NP) and the annulus fibrosus (AF). On the side of NP replacement hydrogels have been extensively tested in vitro and in vivo. However, these gels are usually a trade-off between cell biocompatibility and load-bearing capacity, hydrogels which fulfill both are still lacking. On the side of AF repair much less is known and the question of the anchoring of implants is still to be addressed. New hope for cell therapy comes from developmental biology investigations on the existence of intervertebral disc progenitor cells, which would be an ideal cell source for cell therapy. Also notochordal cells (remnants of the embryonic notochord) have been recently pushed back into focus since these cells have regenerative potential and can activate disc cells. Growth factor treatment and molecular therapies could be less problematic. The biological solutions for NP and AF replacement are still more fiction than fact. However, tissue engineering just scratched the tip of the iceberg, more satisfying solutions are yet to be added to the biomedical pipeline.

Vertebral end-plate fractures as a result of high rate pressure loading in the nucleus of the young adult porcine spine.

PubMed

Brown, Stephen H M; Gregory, Diane E; McGill, Stuart M

2008-01-01

In a healthy spine, end-plate fractures occur from excessive pressurization of the intervening nucleus. Younger spines are most susceptible to such type of injury due to the highly hydraulic nature of their intervertebral discs. The purpose of this paper was to confirm this fracture mechanism of the healthy spine through the pressurization of the nucleus in the absence of external compressive loading. Sixteen functional porcine spine units were dissected and both injection and pressure transducer needles were inserted into the nucleus of the intervertebral disc. Hydraulic fluid was rapidly injected into the nucleus until failure occurred. Peak pressure and rate of pressure development were monitored. Spine units were dissected to determine the type and location of fracture. Fifteen of the 16 spine units fractured (the remaining unit had a degenerated disc). Of the 15 fractures, 13 occurred at the posterior margin of the end-plate along the lines of the growth plates. A slightly exponential relationship was found between peak pressure and its rate of development (R(2) = 0.544). Also, in each of the growth-plate fractured specimens, nuclear material was forcefully emitted, during fracture, from the intervertebral disc into the vertebral foramen. The posterior end-plate fractures produced here are similar to those often seen in young adult humans. This provides insight into a mechanism of fracture development through pressurization of the nucleus that might be seen in older adolescents and younger adults during athletic events or mild trauma.

Temporary Segmental Distraction in a Dog with Degenerative Lumbosacral Stenosis.

PubMed

Willems, Nicole; Kersten, Roel F M R; van Gaalen, Steven M; Öner, F Cumhur; Strijkers, Gustav J; Veraa, Stefanie; Beukers, Martijn; Tryfonidou, Marianna A; Meij, Björn P

2018-06-02

 Degenerative lumbosacral stenosis (DLSS) is characterized by intervertebral disc degeneration and causes lower back pain in dogs. Temporary distraction in rabbit models with induced intervertebral disc degeneration showed signs of intervertebral disc repair. In the present study, we assessed safety and efficacy of temporary segmental distraction in a dog with clinical signs of DLSS.  Distraction of the lumbosacral junction by pedicle screw-rod fixation was applied in a 5-year-old Greyhound with DLSS and evaluated by radiography, magnetic resonance imaging, and force plate analysis before and after distraction.  Safe distraction of the lumbosacral junction was demonstrated, with improvement of clinical signs after removal of the distraction device. Signal intensity of the intervertebral disc showed no changes over time. T2 value was highest directly after removal of the distraction device but decreased by 10% of the preoperative value at 9 months of follow-up. Disc height decreased (8%) immediately after removal of the distraction device, but recovered to the initial value. A decrease in the pelvic/thoracic propulsive force during pedicle screw-rod fixation and distraction was demonstrated, which slowly increased by 4% compared with the initial value.  Temporary pedicle screw-rod fixation in combination with distraction in a dog with DLSS was safe, improved clinical signs and retained disc height at 9 months of follow-up. Schattauer GmbH Stuttgart.

Translation of an engineered nanofibrous disc-like angle-ply structure for intervertebral disc replacement in a small animal model.

PubMed

Martin, John T; Milby, Andrew H; Chiaro, Joseph A; Kim, Dong Hwa; Hebela, Nader M; Smith, Lachlan J; Elliott, Dawn M; Mauck, Robert L

2014-06-01

Intervertebral disc degeneration has been implicated in the etiology of low back pain; however, the current surgical strategies for treating symptomatic disc disease are limited. A variety of materials have been developed to replace disc components, including the nucleus pulposus (NP), the annulus fibrosus (AF) and their combination into disc-like engineered constructs. We have previously shown that layers of electrospun poly(ε-caprolactone) scaffold, mimicking the hierarchical organization of the native AF, can achieve functional parity with native tissue. Likewise, we have combined these structures with cell-seeded hydrogels (as an NP replacement) to form disc-like angle-ply structures (DAPS). The objective of this study was to develop a model for the evaluation of DAPS in vivo. Through a series of studies, we developed a surgical approach to replace the rat caudal disc with an acellular DAPS and then stabilized the motion segment via external fixation. We then optimized cell infiltration into DAPS by including sacrificial poly(ethylene oxide) layers interspersed throughout the angle-ply structure. Our findings illustrate that DAPS are stable in the caudal spine, are infiltrated by cells from the peri-implant space and that infiltration is expedited by providing additional routes for cell migration. These findings establish a new in vivo platform in which to evaluate and optimize the design of functional disc replacements. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Comparison between cranial thoracic intervertebral disc herniations in German Shepherd dogs and other large breed dogs.

PubMed

Gaitero, Luis; Nykamp, Stephanie; Daniel, Rob; Monteith, Gabrielle

2013-01-01

Cranial thoracic intervertebral disc herniations have been reported to be rare in dogs due to the presence of the intercapital ligament, however some studies have proposed they may not be uncommon in German Shepherd dogs. The purpose of this retrospective study was to compare cranial thoracic intervertebral disc herniations in German Shepherd dogs and other large breed dogs (control group). Medical records at the Ontario Veterinary College were searched for German Shepherd dogs and other large breed dogs that had magnetic resonance imaging studies including the T1-T9 region. For each dog and each disc space from T1-T9, three variables (compression, disc degeneration, and herniation) were recorded and graded based on review of sagittal T2-weighted images. Twenty-three German Shepherd dogs and 47 other large breed dogs met inclusion criteria. The German Shepherd dog group had higher scores than the control group for compression (P = 0.0099) and herniation (P < 0.001), but not disc degeneration (P = 0.97). In the German Shepherd dog group, intervertebral discs T2-T3 and T4-T5 had an increased risk for compression and T3-T4 had an increased risk for compression and herniation. Findings from this study indicated that German Shepherd dogs may be more likely than other large breed dogs to have spinal cord compression due to cranial thoracic disc herniations. Imaging of the cranial thoracic spine, including T2-T3, is recommended for German Shepherd dogs with T3-L3 neurological signs. © 2012 Veterinary Radiology & Ultrasound.

Implantation of hyaluronic acid hydrogel prevents the pain phenotype in a rat model of intervertebral disc injury

PubMed Central

Sakai, Daisuke; Dockery, Peter

2018-01-01

Painful intervertebral disc degeneration is mediated by inflammation that modulates glycosylation and induces hyperinnervation and sensory sensitization, which result in discogenic pain. Hyaluronic acid (HA) used as a therapeutic biomaterial can reduce inflammation and pain, but the effects of HA therapy on glycosylation and pain associated with disc degeneration have not been previously determined. We describe a novel rat model of pain induced by intervertebral disc injury, with validation of the pain phenotype by morphine treatment. Using this model, we assessed the efficacy of HA hydrogel for the alleviation of pain, demonstrating that it reduced nociceptive behavior, an effect associated with down-regulation of nociception markers and inhibition of hyperinnervation. Furthermore, HA hydrogel altered glycosylation and modulated key inflammatory and regulatory signaling pathways, resulting in attenuation of inflammation and regulation of matrix components. Our results suggest that HA hydrogel is a promising clinical candidate for the treatment of back pain caused by degenerated discs. PMID:29632893

Accelerated cellular senescence in degenerate intervertebral discs: a possible role in the pathogenesis of intervertebral disc degeneration

PubMed Central

Le Maitre, Christine Lyn; Freemont, Anthony John; Hoyland, Judith Alison

2007-01-01

Current evidence implicates intervertebral disc degeneration as a major cause of low back pain, although its pathogenesis is poorly understood. Numerous characteristic features of disc degeneration mimic those seen during ageing but appear to occur at an accelerated rate. We hypothesised that this is due to accelerated cellular senescence, which causes fundamental changes in the ability of disc cells to maintain the intervertebral disc (IVD) matrix, thus leading to IVD degeneration. Cells isolated from non-degenerate and degenerate human tissue were assessed for mean telomere length, senescence-associated β-galactosidase (SA-β-gal), and replicative potential. Expression of P16INK4A (increased in cellular senescence) was also investigated in IVD tissue by means of immunohistochemistry. RNA from tissue and cultured cells was used for real-time polymerase chain reaction analysis for matrix metalloproteinase-13, ADAMTS 5 (a disintegrin and metalloprotease with thrombospondin motifs 5), and P16INK4A. Mean telomere length decreased with age in cells from non-degenerate tissue and also decreased with progressive stages of degeneration. In non-degenerate discs, there was an age-related increase in cellular expression of P16INK4A. Cells from degenerate discs (even from young patients) exhibited increased expression of P16INK4A, increased SA-β-gal staining, and a decrease in replicative potential. Importantly, there was a positive correlation between P16INK4A and matrix-degrading enzyme gene expression. Our findings indicate that disc cell senescence occurs in vivo and is accelerated in IVD degeneration. Furthermore, the senescent phenotype is associated with increased catabolism, implicating cellular senescence in the pathogenesis of IVD degeneration. PMID:17498290

A Novel, Minimally-Invasive Approach to Repair Degenerative Disk Disease in an Ovine Model Using Injectable Polymethyl-Methacrylate and Bovine Collagen (PMMA/BC)

PubMed Central

Feldman, Erica; Narayan, Anisha; Taylor, William

2016-01-01

Background : The natural, inflammatory repair processes of an injured intervertebral degenerative disc can propagate further injury and destruction. While there are many different treatment modalities of the pain related to degenerative disc disease, none are actually reparative in nature. Treatment strategies to repair a degenerative disc without inducing a destructive inflammatory milieu have been elusive.  Purpose: The purpose of this experiment is to discover the feasibility of reconstructing an injured intervertebral disc using an injected, inert polymer as the foundation for endogenous collagen growth. Study Design: In this ovine model of six subjects in total, we introduce a modality where a large inert polymer, polymethyl methacrylate (PMMA), in conjunction bovine collagen (BC) is injected into the intervertebral disc. Following six months of observation, histologic specimens were evaluated macroscopically and microscopically for evidence of a benefit of the injectable PMMA/BC. Methods: We obtained six merino sheep for this study. Concentric injuries were made to four of their lumbar intervertebral discs. Two of those levels were treated with a percutaneous injection of 0.3 cc of PMMA/BC. The remaining lumbar levels were left untreated and were our controls. After six months, all subjects were sacrificed. Their four levels were extracted and were examined macroscopically and microscopically. Results: All subjects tolerated the lumbar injury and percutaneous injection of PMMA/BC well. After the six month interval, all subjects have demonstrated an intact architecture of their lumbar disc height at the macroscopic and microscopic level. Microscopically, there was no evidence of external migration of the PMMA/BC microspheres, nor was there any evidence of an inflammatory response by its presence. Notably, the PMMA/BC microspheres were well-incorporated into the concentric disc tears and had undergone endogenous collagen formation in its environment. Treatment levels were revealing for maintenance of disc height without evidence of an ongoing degeneration. The controlled levels were revealing for continued disc degeneration with loss of disc height and evolving injury at the level of the concentric tear. Conclusions: This ovine model demonstrates a novel and promising technique for prevention and arrest of lumbar intervertebral disc degeneration. PMID:27630802

Continuous lumbar hemilaminectomy for intervertebral disc disease in an Amur tiger (Panthera tigris altaica).

PubMed

Flegel, Thomas; Böttcher, Peter; Alef, Michaele; Kiefer, Ingmar; Ludewig, Eberhard; Thielebein, Jens; Grevel, Vera

2008-09-01

A 13-yr-old Amur tiger (Panthera tigris altaica) was presented for an acute onset of paraplegia. Spinal imaging that included plain radiographs, myelography, and computed tomography performed under general anesthesia revealed lateralized spinal cord compression at the intervertebral disc space L4-5 caused by intervertebral disc extrusion. This extrusion was accompanied by an extensive epidural hemorrhage from L3 to L6. Therefore, a continuous hemilaminectomy from L3 to L6 was performed, resulting in complete decompression of the spinal cord. The tiger was ambulatory again 10 days after the surgery. This case suggests that the potential benefit of complete spinal cord decompression may outweigh the risk of causing clinically significant spinal instability after extensive decompression.

Elastic fibre organization in the intervertebral discs of the bovine tail

PubMed Central

Yu, Jing; Peter, C; Roberts, Sally; Urban, Jill PG

2002-01-01

Elastic fibres have been revealed by both elastin immunostaining and conventional histological orcein-staining in the intervertebral discs of the bovine tail. These fibres are distributed in all regions of the disc but their organization varies from region to region. In the centre of the nucleus, long (>150 μm) elastic fibres are orientated radially. In the transitional region between nucleus and annulus, the orientation of the elastic fibres changes, producing a criss-cross pattern. In the annulus itself, elastic fibres appear densely distributed in the region between the lamellae and also in ‘bridges’ across the lamellae, particularly in the adult. Elastic fibres are apparent within the lamellae, orientated parallel to the collagen fibres of each lamella, particularly in the young (12-day-old) discs. In the region between the disc and the cartilaginous endplate, elastic fibres appear to anchor into the plate and terminate there. The results of this study suggest that elastic fibres contribute to the mechanical functioning of the intervertebral disc. The varying organization of the elastic fibres in the different regions of the disc is likely to relate to the different regional loading patterns PMID:12489758

Intercellular signaling pathways active during intervertebral disc growth, differentiation, and aging.

PubMed

Dahia, Chitra Lekha; Mahoney, Eric J; Durrani, Atiq A; Wylie, Christopher

2009-03-01

Intervertebral discs at different postnatal ages were assessed for active intercellular signaling pathways. To generate a spatial and temporal map of the signaling pathways active in the postnatal intervertebral disc (IVD). The postnatal IVD is a complex structure, consisting of 3 histologically distinct components, the nucleus pulposus, fibrous anulus fibrosus, and endplate. These differentiate and grow during the first 9 weeks of age in the mouse. Identification of the major signaling pathways active during and after the growth and differentiation period will allow functional analysis using mouse genetics and identify targets for therapy for individual components of the disc. Antibodies specific for individual cell signaling pathways were used on cryostat sections of IVD at different postnatal ages to identify which components of the IVD were responding to major classes of intercellular signal, including sonic hedgehog, Wnt, TGFbeta, FGF, and BMPs. We present a spatial/temporal map of these signaling pathways during growth, differentiation, and aging of the disc. During growth and differentiation of the disc, its different components respond at different times to different intercellular signaling ligands. Most of these are dramatically downregulated at the end of disc growth.

Age-related changes in expression of transforming growth factor-beta and receptors in cells of intervertebral discs.

PubMed

Matsunaga, Shunji; Nagano, Satoshi; Onishi, Toshiyuki; Morimoto, Norio; Suzuki, Shusaku; Komiya, Setsuro

2003-01-01

The authors conducted a study to determine age-related changes in expression of transforming growth factor (TGF)-beta1, -beta2, -beta3, and Type I and Type II receptors in various cells in the nucleus pulposus and anulus fibrosus. Immunolocalization of TGFbetas and Type I and II receptors was examined during the aging process of cervical intervertebral discs in senescence-accelerated mice (SAM). The TGFbeta family has important roles for cellular function of various tissues. Its role in disc aging, however, is unknown. Detailed information on the temporal and spatial localization of TGFbetas and their receptors in discs is required before discussing introduction of them clinically into the intervertebral disc. Three groups of five SAM each were used. The groups of SAM were age 8, 24, and 50 weeks, respectively. Hematoxylin and eosin staining and immunohistochemical study involving specific antibodies for TGFbeta1, -beta2, -beta3, and Types I and II TGF receptors were performed. Intervertebral discs exhibited degenerative change with advancing age. The TGFbetas and their receptors were present in the fibrocartilaginous cells within the anulus fibrosus and notochord-like cells within the nucleus pulposus of young mice. Expression of TGFbetas and Type I and Type II receptors changed markedly in the cells within the anulus fibrosus during the aging process. The TGFbetas and their receptors were present in cells within the nucleus pulposus and the anulus fibrosus of young mice, and their expression decreased with age.

Preflight, In-Flight, and Postflight Imaging of the Cervical and Lumbar Spine in Astronauts.

PubMed

Harrison, Michael F; Garcia, Kathleen M; Sargsyan, Ashot E; Ebert, Douglas; Riascos-Castaneda, Roy F; Dulchavsky, Scott A

2018-01-01

Back pain is a common complaint during spaceflight that is commonly attributed to intervertebral disc swelling in microgravity. Ultrasound (US) represents the only imaging modality on the International Space Station (ISS) to assess its etiology. The present study investigated: 1) The agreement and correlation of spinal US assessments as compared to results of pre- and postflight MRI studies; and 2) the trend in intervertebral disc characteristics over the course of spaceflight to ISS. Seven ISS astronauts underwent pre- and postflight US examinations that included anterior disc height and anterior intervertebral angles with comparison to pre- and postflight MRI results. In-flight US images were analyzed for changes in disc height and angle. Statistical analysis included repeated measures ANOVA with Bonferroni post hoc analysis, Bland-Altman plots, and Pearson correlation. Bland-Altman plots revealed significant disagreement between disc heights and angles for MRI and US measurements while significant Pearson correlations were found in MRI and US measurements for lumbar disc height (r2 = 0.83) and angle (r2 = 0.89), but not for cervical disc height (r2 = 0.26) or angle (r2 = 0.02). Changes in anterior intervertebral disc angle-initially increases followed by decreases-were observed in the lumbar and cervical spine over the course of the long-duration mission. The cervical spine demonstrated a loss of total disc height during in-flight assessments (∼0.5 cm). Significant disagreement but significant correlation was noted between US and MRI measurements of disc height and angle. Consistency in imaging modality is important for trending measurements and more research related to US technique is required.Harrison MF, Garcia KM, Sargsyan AE, Ebert D, Riascos-Castaneda RF, Dulchavsky SA. Preflight, in-flight, and postflight imaging of the cervical and lumbar spine in astronauts. Aerosp Med Hum Perform. 2018; 89(1):32-40.

Notochord to Nucleus Pulposus Transition.

PubMed

Lawson, Lisa; Harfe, Brian D

2015-10-01

A tissue that commonly deteriorates in older vertebrates is the intervertebral disc, which is located between the vertebrae. Age-related changes in the intervertebral discs are thought to cause most cases of back pain. Back pain affects more than half of people over the age of 65, and the treatment of back pain costs 50-100 billion dollars per year in the USA. The normal intervertebral disc is composed of three distinct regions: a thick outer ring of fibrous cartilage called the annulus fibrosus, a gel-like material that is surrounded by the annulus fibrosus called the nucleus pulposus, and superior and inferior cartilaginous end plates. The nucleus pulposus has been shown to be critical for disc health and function. Damage to this structure often leads to disc disease. Recent reports have demonstrated that the embryonic notochord, a rod-like structure present in the midline of vertebrate embryos, gives rise to all cell types found in adult nuclei pulposi. The mechanism responsible for the transformation of the notochord into nuclei pulposi is unknown. In this review, we discuss potential molecular and physical mechanisms that may be responsible for the notochord to nuclei pulposi transition.

Optical methods for diagnostics and feedback control in laser-induced regeneration of spine disc and joint cartilages

NASA Astrophysics Data System (ADS)

Sobol, Emil; Sviridov, Alexander; Omeltchenko, Alexander; Baum, Olga; Baskov, Andrey; Borchshenko, Igor; Golubev, Vladimir; Baskov, Vladimir

2011-03-01

In 1999 we have introduced a new approach for treatment of spine diseases based on the mechanical effect of nondestructive laser radiation on the nucleus pulposus of the intervertebral disc. Laser reconstruction of spine discs (LRD) involves puncture of the disc and non-destructive laser irradiation of the nucleus pulposus to activate reparative processes in the disc tissues. In vivo animal study has shown that LRD allows activate the growth of hyaline type cartilage in laser affected zone. The paper considers physical processes and mechanisms of laser regeneration, presents results of investigations aimed to optimize laser settings and to develop feedback control system for laser reparation in cartilages of spine and joints. The results of laser reconstruction of intervertebral discs for 510 patients have shown substantial relief of back pain for 90% of patients. Laser technology has been experimentally tested for reparation of traumatic and degenerative diseases in joint cartilage of 20 minipigs. It is shown that laser regeneration of cartilage allows feeling large (more than 5 mm) defects which usually never repair on one's own. Optical techniques have been used to promote safety and efficacy of the laser procedures.

Chymodiactin in patients with herniated lumbar intervertebral disc(s). An open-label, multicenter study.

PubMed

McDermott, D J; Agre, K; Brim, M; Demma, F J; Nelson, J; Wilson, R R; Thisted, R A

1985-04-01

To extent the safety information for Chymodiactin (chymopapain for injection), 37 neurologic and orthopedic surgeons conducted an open-label, multicenter, phase 3 clinical study. A total of 1,498 patients with one or two herniated lumbar intervertebral discs were enrolled. Therapeutic results were generally favorable, with the percentages of patients achieving either excellent or good (or successful) results ranging from 79.6% to 88.9%, depending on criteria employed in the tabulation. There were 13 cases of anaphylaxis, and 2 of these patients died of complications of anaphylaxis. Two additional patients experienced serious neurologic problems. The first of these two patients developed transverse myelitis and paraplegia approximately 3 weeks following chemonucleolysis. Transdural discograms at three levels had been done approximately 2 days prior to chemonucleolysis, in violation of the protocol. The second patient developed acute cauda equina syndrome, and, despite emergency laminectomy, had permanent neurologic sequelae. Back spasm and stiffness/soreness were the most frequently encountered adverse experiences.

Ranges of Cervical Intervertebral Disc Deformation During an In Vivo Dynamic Flexion–Extension of the Neck

PubMed Central

Yu, Yan; Mao, Haiqing; Li, Jing-Sheng; Tsai, Tsung-Yuan; Cheng, Liming; Wood, Kirkham B.; Li, Guoan; Cha, Thomas D.

2017-01-01

While abnormal loading is widely believed to cause cervical spine disc diseases, in vivo cervical disc deformation during dynamic neck motion has not been well delineated. This study investigated the range of cervical disc deformation during an in vivo functional flexion–extension of the neck. Ten asymptomatic human subjects were tested using a combined dual fluoroscopic imaging system (DFIS) and magnetic resonance imaging (MRI)-based three-dimensional (3D) modeling technique. Overall disc deformation was determined using the changes of the space geometry between upper and lower endplates of each intervertebral segment (C3/4, C4/5, C5/6, and C6/7). Five points (anterior, center, posterior, left, and right) of each disc were analyzed to examine the disc deformation distributions. The data indicated that between the functional maximum flexion and extension of the neck, the anterior points of the discs experienced large changes of distraction/compression deformation and shear deformation. The higher level discs experienced higher ranges of disc deformation. No significant difference was found in deformation ranges at posterior points of all the discs. The data indicated that the range of disc deformation is disc level dependent and the anterior region experienced larger changes of deformation than the center and posterior regions, except for the C6/7 disc. The data obtained from this study could serve as baseline knowledge for the understanding of the cervical spine disc biomechanics and for investigation of the biomechanical etiology of disc diseases. These data could also provide insights for development of motion preservation surgeries for cervical spine. PMID:28334358

Ranges of Cervical Intervertebral Disc Deformation During an In Vivo Dynamic Flexion-Extension of the Neck.

PubMed

Yu, Yan; Mao, Haiqing; Li, Jing-Sheng; Tsai, Tsung-Yuan; Cheng, Liming; Wood, Kirkham B; Li, Guoan; Cha, Thomas D

2017-06-01

While abnormal loading is widely believed to cause cervical spine disc diseases, in vivo cervical disc deformation during dynamic neck motion has not been well delineated. This study investigated the range of cervical disc deformation during an in vivo functional flexion-extension of the neck. Ten asymptomatic human subjects were tested using a combined dual fluoroscopic imaging system (DFIS) and magnetic resonance imaging (MRI)-based three-dimensional (3D) modeling technique. Overall disc deformation was determined using the changes of the space geometry between upper and lower endplates of each intervertebral segment (C3/4, C4/5, C5/6, and C6/7). Five points (anterior, center, posterior, left, and right) of each disc were analyzed to examine the disc deformation distributions. The data indicated that between the functional maximum flexion and extension of the neck, the anterior points of the discs experienced large changes of distraction/compression deformation and shear deformation. The higher level discs experienced higher ranges of disc deformation. No significant difference was found in deformation ranges at posterior points of all the discs. The data indicated that the range of disc deformation is disc level dependent and the anterior region experienced larger changes of deformation than the center and posterior regions, except for the C6/7 disc. The data obtained from this study could serve as baseline knowledge for the understanding of the cervical spine disc biomechanics and for investigation of the biomechanical etiology of disc diseases. These data could also provide insights for development of motion preservation surgeries for cervical spine.

Kinematic Evaluation of Association between Disc Bulge Migration, Lumbar Segmental Mobility, and Disc Degeneration in the Lumbar Spine Using Positional Magnetic Resonance Imaging

PubMed Central

Hu, Jonathan K.; Morishita, Yuichiro; Montgomery, Scott R.; Hymanson, Henry; Taghavi, Cyrus E.; Do, Duc; Wang, Jeff C.

2011-01-01

Degenerative disc disease and disc bulge in the lumbar spine are common sources of lower back pain. Little is known regarding disc bulge migration and lumbar segmental mobility as the lumbar spine moves from flexion to extension. In this study, 329 symptomatic (low back pain with or without neurological symptoms) patients with an average age of 43.5 years with varying degrees of disc degeneration were examined to characterize the kinematics of the lumbar intervertebral discs through flexion, neutral, and extension weight-bearing positions. In this population, disc bulge migration associated with dynamic motion of the lumbar spine significantly increased with increased grade of disk degeneration. Although no obvious trends relating the migration of disc bulge and angular segmental mobility were seen, translational segmental mobility tended to increase with disc bulge migration in all of the degenerative disc states. It appears that many factors, both static (intervertebral disc degeneration or disc height) and dynamic (lumbar segmental mobility), affect the mechanisms of lumbar disc bulge migration. PMID:24353937

A Structurally and Functionally Biomimetic Biphasic Scaffold for Intervertebral Disc Tissue Engineering

PubMed Central

Choy, Andrew Tsz Hang; Chan, Barbara Pui

2015-01-01

Tissue engineering offers high hopes for the treatment of intervertebral disc (IVD) degeneration. Whereas scaffolds of the disc nucleus and annulus have been extensively studied, a truly biomimetic and mechanically functional biphasic scaffold using naturally occurring extracellular matrix is yet to be developed. Here, a biphasic scaffold was fabricated with collagen and glycosaminoglycans (GAGs), two of the most abundant extracellular matrix components in the IVD. Following fabrication, the scaffold was characterized and benchmarked against native disc. The biphasic scaffold was composed of a collagen-GAG co-precipitate making up the nucleus pulposus-like core, and this was encapsulated in multiple lamellae of photochemically crosslinked collagen membranes comprising the annulus fibrosus-like lamellae. On mechanical testing, the height of our engineered disc recovered by ~82-89% in an annulus-independent manner, when compared with the 99% recovery exhibited by native disc. The annulus-independent nature of disc height recovery suggests that the fluid replacement function of the engineered nucleus pulposus core might mimic this hitherto unique feature of native disc. Biphasic scaffolds comprised of 10 annulus fibrosus-like lamellae had the best overall mechanical performance among the various designs owing to their similarity to native disc in most aspects, including elastic compliance during creep and recovery, and viscous compliance during recovery. However, the dynamic mechanical performance (including dynamic stiffness and damping factor) of all the biphasic scaffolds was similar to that of the native discs. This study contributes to the rationalized design and development of a biomimetic and mechanically viable biphasic scaffold for IVD tissue engineering. PMID:26115332

Pathogenesis of lumbar spine disease in mucopolysaccharidosis VII

PubMed Central

Smith, Lachlan J; Baldo, Guilherme; Wu, Susan; Liu, Yuli; Whyte, Michael P; Giugliani, Roberto; Elliott, Dawn M; Haskins, Mark E; Ponder, Katherine P

2012-01-01

Mucopolysaccharidosis type VII (MPS VII) is characterized by deficient β-glucuronidase (GUSB) activity, which leads to accumulation of chondroitin, heparan and dermatan sulfate glycosaminoglycans (GAGs), and multisystemic disease. MPS VII patients can develop kypho-scoliotic deformity and spinal cord compression due to disease of intervertebral discs, vertebral bodies, and associated tissues. We have previously demonstrated in MPS VII dogs that intervertebral discs degenerate, vertebral bodies have irregular surfaces, and vertebral body epiphyses have reduced calcification, but the pathophysiological mechanisms underlying these changes are unclear. We hypothesized that some of these manifestations could be due to upregulation of destructive proteases, possibly via the binding of GAGs to Toll-like receptor 4 (TLR4), as has been proposed for other tissues in MPS models. In this study, the annulus fibrosus of the intervertebral disc of 6 month-old MPS VII dogs had cathepsin B and K activities that were 117- and 2-fold normal, respectively, which were associated with elevations in mRNA levels for cathepsins as well as TLR4. The epiphyses of MPS VII dogs had a marked elevation in mRNA for the cartilage-associated gene collagen II, consistent with a developmental delay in the conversion of the cartilage to bone in this region. A spine from a human patient with MPS VII exhibited similar increased cartilage in the vertebral bodies adjacent to the end plates, disorganization of the intervertebral discs, and irregular vertebral end plate morphology. These data suggest that the pathogenesis of destructive changes in the spine in MPS VII may involve upregulation of cathepsins. Inhibition of destructive proteases, such as cathepsins, might reduce spine disease in patients with MPS VII or related disorders. PMID:22513347

Mechanoreceptors in Diseased Cervical Intervertebral Disc and Vertigo.

PubMed

Yang, Liang; Yang, Cheng; Pang, Xiaodong; Li, Duanming; Yang, Hong; Zhang, Xinwu; Yang, Yi; Peng, Baogan

2017-04-15

We collected the samples of cervical intervertebral discs from patients with vertigo to examine the distribution and types of mechanoreceptors in diseased cervical disc. The aim of this study was to determine whether mechanoreceptors are distributed more abundantly in cervical discs from patients with cervical spondylosis, and whether they are related to vertigo. Previous limited studies have found that normal cervical intervertebral discs are supplied with mechanoreceptors that have been considered responsible for proprioceptive functions. Several clinical studies have indicated that the patients with cervical spondylosis manifested significantly impaired postural control and subjective balance disturbance. We collected 77 samples of cervical discs from 62 cervical spondylosis patients without vertigo, 61 samples from 54 patients with vertigo, and 40 control samples from 8 cadaveric donors to investigate distribution of mechanoreceptors containing neurofilament (NF200) and S-100 protein immunoreactive nerve endings. The immunohistochemical investigation revealed that the most frequently encountered mechanoreceptors were the Ruffini corpuscles in all groups of cervical disc samples. They were obviously increased in the number and deeply ingrown into inner annulus fibrosus and even into nucleus pulposus in the diseased cervical discs from patients with vertigo in comparison with the discs from patients without vertigo and control discs. Only three Golgi endings were seen in the three samples from patients with vertigo. No Pacinian corpuscles were found in any samples of cervical discs. The diseased cervical discs from patients with vertigo had more abundant distribution of Ruffini corpuscles than other discs. A positive association between the increased number and ingrowth of Ruffini corpuscles in the diseased cervical disc and the incidence of vertigo in the patients with cervical spondylosis was found, which may indicate a key role of Ruffini corpuscles in the pathogenesis of vertigo of cervical origin. 1.

Imaging of degenerative lumbar intervertebral discs; linking anatomy, pathology and imaging.

PubMed

Adams, Ashok; Roche, Oran; Mazumder, Asif; Davagnanam, Indran; Mankad, Kshitij

2014-09-01

Low back pain is a common medical condition that has significant implications for healthcare providers and the UK economy. Low back pain can be classified as 'specific' in which an underlying pathophysiological mechanism is identified (eg, herniated intervertebral disc). Advanced imaging should be performed in this situation and in those patients in whom systemic disease is strongly suspected. In the majority (approximately 90%), low back pain in 'non specific' and there is a weak correlation with imaging abnormalities. This is an area of ongoing research and remains controversial in terms of imaging approach and treatment (eg, theory of discogenic pain, interpretation and treatment of endplate changes). With regards Modic endplate changes, current research suggests that an infective component may be involved that may identify novel potential treatments in patients with chronic low back pain refractory to other treatment modalities. MRI is the imaging modality of choice for the assessment of degenerative changes in intervertebral discs. MRI has superior soft tissue contrast resolution when compared to other imaging modalities (eg, plain radiography, CT). An understanding of normal anatomy and MR appearances of intervertebral discs, particularly with regards to how these appearances change with advancing age, is required to aid image interpretation. Knowledge of the spectrum of degenerative processes that may occur in the intervertebral discs is required in order to identify and explain abnormal MRI appearances. As the communication of MRI findings may guide therapeutic decision making and surgical intervention, the terminology used by radiologists must be accurate and consistent. Therefore, description of degenerative disc changes in the current paper is based on the most up-to-date recommendations, the aim being to aid reporting by radiologists and interpretation of reports by referring clinicians. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Formation of lamellar cross bridges in the annulus fibrosus of the intervertebral disc is a consequence of vascular regression.

PubMed

Smith, Lachlan J; Elliott, Dawn M

2011-05-01

Cross bridges are radial structures within the highly organized lamellar structure of the annulus fibrosus of the intervertebral disc that connect two or more non-consecutive lamellae. Their origin and function are unknown. During fetal development, blood vessels penetrate deep within the AF and recede during postnatal growth. We hypothesized that cross bridges are the pathways left by these receding blood vessels. Initially, the presence of cross bridges was confirmed in cadaveric human discs aged 25 and 53 years. Next, L1-L2 intervertebral discs (n=4) from sheep ranging in age from 75 days fetal gestation to adult were processed for paraffin histology. Mid-sagittal sections were immunostained for endothelial cell marker PECAM-1. The anterior and posterior AF were imaged using differential interference contrast microscopy, and the following parameters were quantified: total number of distinct lamellae, total number of cross bridges, percentage of cross bridges staining positive for PECAM-1, cross bridge penetration depth (% total lamellae), and PECAM-1 positive cross bridge penetration depth. Cross bridges were first observed at 100 days fetal gestation. The overall number peaked in neonates then remained relatively unchanged. The percentage of PECAM-1 positive cross bridges declined progressively from almost 100% at 100 days gestation to less than 10% in adults. Cross bridge penetration depth peaked in neonates then remained unchanged at subsequent ages. Depth of PECAM-1 positive cross bridges decreased progressively after birth. Findings were similar for both the anterior and posterior. The AF lamellar architecture is established early in development. It later becomes disrupted as a consequence of vascularization. Blood vessels then recede, perhaps due to increasing mechanical stresses in the surrounding matrix. In this study we present evidence that the pathways left by receding blood vessels remain as lamellar cross bridges. It is unclear whether the presence of cross bridges in the aging and degenerating intervertebral disc would be advantageous or detrimental, and this question should be addressed by future studies. Copyright © 2011 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

Percutaneous endoscopic intra-annular subligamentous herniotomy for large central disc herniation: a technical case report.

PubMed

Lee, Sang-Ho; Choi, Kyung-Chul; Baek, Oon Ki; Kim, Ho Jin; Yoo, Seung-Hwa

2014-04-01

Technical case report. To describe the novel technique of percutaneous endoscopic herniotomy using a unilateral intra-annular subligamentous approach for the treatment of large centrally herniated discs. Open discectomy for large central disc herniations may have poor long-term prognosis due to heavy loss of intervertebral disc tissue, segmental instability, and recurrence of pain. Six consecutive patients who presented with back and leg pain, and/or weakness due to a large central disc herniation were treated using percutaneous endoscopic herniotomy with a unilateral intra-annular subligamentous approach. The patients experienced relief of symptoms and intervertebral disc spaces were well maintained. The annular defects were noted to be in the process of healing and recovery. Percutaneous endoscopic unilateral intra-annular subligamentous herniotomy was an effective and affordable minimally invasive procedure for patients with large central disc herniations, allowing preservation of nonpathological intradiscal tissue through a concentric outer-layer annular approach.

Effect of collagen fibre orientation on intervertebral disc torsion mechanics.

PubMed

Yang, Bo; O'Connell, Grace D

2017-12-01

The intervertebral disc is a complex fibro-cartilaginous material, consisting of a pressurized nucleus pulposus surrounded by the annulus fibrosus, which has an angle-ply structure. Disc injury and degeneration are noted by significant changes in tissue structure and function, which significantly alters stress distribution and disc joint stiffness. Differences in fibre orientation are thought to contribute to changes in disc torsion mechanics. Therefore, the objective of this study was to evaluate the effect of collagen fibre orientation on internal disc mechanics under compression combined with axial rotation. We developed and validated a finite element model (FEM) to delineate changes in disc mechanics due to fibre orientation from differences in material properties. FEM simulations were performed with fibres oriented at [Formula: see text] throughout the disc (uniform by region and fibre layer). The initial model was validated by published experimental results for two load conditions, including [Formula: see text] axial compression and [Formula: see text] axial rotation. Once validated, fibre orientation was rotated by [Formula: see text] or [Formula: see text] towards the horizontal plane, resulting in a decrease in disc joint torsional stiffness. Furthermore, we observed that axial rotation caused a sinusoidal change in disc height and radial bulge, which may be beneficial for nutrient transport. In conclusion, including anatomically relevant fibre angles in disc joint FEMs is important for understanding stress distribution throughout the disc and will be important for understanding potential causes for disc injury. Future models will include regional differences in fibre orientation to better represent the fibre architecture of the native disc.

Mechanical Characterization of the Human Lumbar Intervertebral Disc Subjected to Impact Loading Conditions

NASA Astrophysics Data System (ADS)

Jamison, David, IV

Low back pain is a large and costly problem in the United States. Several working populations, such as miners, construction workers, forklift operators, and military personnel, have an increased risk and prevalence of low back pain compared to the general population. This is due to exposure to repeated, transient impact shocks, particularly while operating vehicles or other machinery. These shocks typically do not cause acute injury, but rather lead to pain and injury over time. The major focus in low back pain is often the intervertebral disc, due to its role as the major primary load-bearing component along the spinal column. The formation of a reliable standard for human lumbar disc exposure to repeated transient shock could potentially reduce injury risk for these working populations. The objective of this project, therefore, is to characterize the mechanical response of the lumbar intervertebral disc subjected to sub-traumatic impact loading conditions using both cadaveric and computational models, and to investigate the possible implications of this type of loading environment for low back pain. Axial, compressive impact loading events on Naval high speed boats were simulated in the laboratory and applied to human cadaveric specimen. Disc stiffness was higher and hysteresis was lower than quasi-static loading conditions. This indicates a shift in mechanical response when the disc is under impact loads and this behavior could be contributing to long-term back pain. Interstitial fluid loss and disc height changes were shown to affect disc impact mechanics in a creep study. Neutral zone increased, while energy dissipation and low-strain region stiffness decreased. This suggests that the disc has greater clinical instability during impact loading with progressive creep and fluid loss, indicating that time of day should be considered for working populations subjected to impact loads. A finite element model was developed and validated against cadaver specimen subjected to impacts in the laboratory. Analysis showed greater total von Mises stress and pore pressure in the components of the disc under transient shocks compared to static or quasi-static loading. These findings support the idea that impact shocks cause a change in mechanical response and are potentially damaging to the disc in the long term.

SHH-dependent knockout of HIF-1 alpha accelerates the degenerative process in mouse intervertebral disc.

PubMed

Wu, W J; Zhang, X K; Zheng, X F; Yang, Y H; Jiang, S D; Jiang, L S

2013-01-01

Hypoxia-inducible factor-1alpha (HIF-1 alpha) has been reported to have an important role in the metabolism and synthesis of extracellular matrix of the nucleus pulposus cells (NPCs) and was assumed to be involved in the process of intervertebral disc degeneration. The objective of this study was to investigate the role of HIF-1alpha in disc degeneration in vivo using a conditional HIF-1alpha knockout (KO) mouse model. ShhCre transgenic mice were mated with HIF-1 alpha fl/fl mice to generate conditional HIF-1alpha KO mice (HIF-1alpha fl/fl-ShhCre+). Three mice of each genotype (Wide-type and HIF-1alpha KO) at the age of 3 days, 6, and 12 weeks were sacrificed after genotyping. Five lumbar disc samples were harvested from each mouse, with a total of 45 disc samples for each genotype. In situ hybridization and immunohistochemical analysis were used to check the efficacy of HIF-1alpha knockout. Histological grading of the disc degeneration was performed according to the classification system proposed by Boos et al. Picro-sirius red staining, Safranine O/fast green staining and immunohistochemical study were used to evaluate the expression of aggrecan, type-II collagen and vascular endothelial growth factor (VEGF). Histologic analysis revealed more NPC deaths and signs of degeneration in HIF-1alpha KO mice and the degeneration scores of HIF-1alpha KO mice were significantly higher than those of the Wide-type mice at the age of 6 weeks and 12 weeks. There were less expressions of aggrecan, type-II collagen and VEGF in the intervertebral discs of HIF1-alpha KO mice than in those of wild-type mice. Taken together, the results of our study indicated that HIF-1alpha is a pivotal contributor to NPC survival and the homeotasis of extracellular matrix through the HIF-1alpha/VEGF signaling pathway, and plays an important role in the development of disc degeneration.

Enhancing cell migration in shape-memory alginate-collagen composite scaffolds: In vitro and ex vivo assessment for intervertebral disc repair.

PubMed

Guillaume, Olivier; Naqvi, Syeda Masooma; Lennon, Kerri; Buckley, Conor Timothy

2015-04-01

Lower lumbar disc disorders pose a significant problem in an aging society with substantial socioeconomic consequences. Both inner tissue (nucleus pulposus) and outer tissue (annulus fibrosus) of the intervertebral disc are affected by such debilitating disorders and can lead to disc herniation and lower back pain. In this study, we developed an alginate-collagen composite porous scaffold with shape-memory properties to fill defects occurring in annulus fibrosus tissue of degenerated intervertebral discs, which has the potential to be administered using minimal invasive surgery. In the first part of this work, we assessed how collagen incorporation on preformed alginate scaffolds influences the physical properties of the final composite scaffold. We also evaluated the ability of annulus fibrosus cells to attach, migrate, and proliferate on the composite alginate-collagen scaffolds compared to control scaffolds (alginate only). In vitro experiments, performed in intervertebral disc-like microenvironmental conditions (low glucose and low oxygen concentrations), revealed that for alginate only scaffolds, annulus fibrosus cells agglomerated in clusters with limited infiltration and migration capacity. In comparison, for alginate-collagen scaffolds, annulus fibrosus cells readily attached and colonized constructs, while preserving their typical fibroblastic-like cell morphology with spreading behavior and intense cytoskeleton expression. In a second part of this study, we investigated the effects of alginate-collagen scaffold when seeded with bone marrow derived mesenchymal stem cells. In vitro, we observed that alginate-collagen porous scaffolds supported cell proliferation and extracellular matrix deposition (collagen type I), with secretion amplified by the local release of transforming growth factor-β3. In addition, when cultured in ex vivo organ defect model, alginate-collagen scaffolds maintained viability of transplanted mesenchymal stem cells for up to 5 weeks. Taken together, these findings illustrate the advantages of incorporating collagen as a means to enhance cell migration and proliferation in porous scaffolds which could be used to augment tissue repair strategies. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

The relationship between chronic type III acromioclavicular joint dislocation and cervical spine pain

PubMed Central

2009-01-01

Background This study was aimed at evaluating whether or not patients with chronic type III acromioclavicular dislocation develop cervical spine pain and degenerative changes more frequently than normal subjects. Methods The cervical spine of 34 patients with chronic type III AC dislocation was radiographically evaluated. Osteophytosis presence was registered and the narrowing of the intervertebral disc and cervical lordosis were evaluated. Subjective cervical symptoms were investigated using the Northwick Park Neck Pain Questionnaire (NPQ). One-hundred healthy volunteers were recruited as a control group. Results The rate and distribution of osteophytosis and narrowed intervertebral disc were similar in both of the groups. Patients with chronic AC dislocation had a lower value of cervical lordosis. NPQ score was 17.3% in patients with AC separation (100% = the worst result) and 2.2% in the control group (p < 0.05). An inverse significant nonparametric correlation was found between the NPQ value and the lordosis degree in the AC dislocation group (p = 0.001) wheras results were not correlated (p = 0.27) in the control group. Conclusions Our study shows that chronic type III AC dislocation does not interfere with osteophytes formation or intervertebral disc narrowing, but that it may predispose cervical hypolordosis. The higher average NPQ values were observed in patients with chronic AC dislocation, especially in those that developed cervical hypolordosis. PMID:20015356

A Large Animal Model that Recapitulates the Spectrum of Human Intervertebral Disc Degeneration

PubMed Central

Gullbrand, Sarah E.; Malhotra, Neil R.; Schaer, Thomas P.; Zawacki, Zosia; Martin, John T.; Bendigo, Justin R.; Milby, Andrew H.; Dodge, George R.; Vresilovic, Edward J.; Elliott, Dawn M.; Mauck, Robert L.; Smith, Lachlan J.

2016-01-01

Objective The objective of this study was to establish a large animal model that recapitulates the spectrum of intervertebral disc degeneration that occurs in humans and which is suitable for pre-clinical evaluation of a wide range of experimental therapeutics. Design Degeneration was induced in the lumbar intervertebral discs of large frame goats by either intradiscal injection of chondroitinase ABC (ChABC) over a range of dosages (0.1U, 1U or 5U) or subtotal nucleotomy. Radiographs were used to assess disc height changes over 12 weeks. Degenerative changes to the discs and endplates were assessed via magnetic resonance imaging (MRI), semi-quantitative histological grading, micro-computed tomography (µCT), and measurement of disc biomechanical properties. Results Degenerative changes were observed for all interventions that ranged from mild (0.1U ChABC) to moderate (1U ChABC and nucleotomy) to severe (5U ChABC). All groups showed progressive reductions in disc height over 12 weeks. Histological scores were significantly increased in the 1U and 5U ChABC groups. Reductions in T2 and T1ρ, and increased Pfirrmann grade were observed on MRI. Resorption and remodeling of the cortical boney endplate adjacent to ChABC injected discs also occurred. Spine segment range of motion was greater and compressive modulus was lower in 1U ChABC and nucleotomy discs compared to intact. Conclusions A large animal model of disc degeneration was established that recapitulates the spectrum of structural, compositional and biomechanical features of human disc degeneration. This model may serve as a robust platform for evaluating the efficacy of therapeutics targeted towards varying degrees of disc degeneration. PMID:27568573

Novel Human Intervertebral Disc Strain Template to Quantify Regional Three-Dimensional Strains in a Population and Compare to Internal Strains Predicted by a Finite Element Model

PubMed Central

Showalter, Brent L.; DeLucca, John F.; Peloquin, John M.; Cortes, Daniel H.; Yoder, Jonathon H.; Jacobs, Nathan T.; Wright, Alexander C.; Gee, James C.; Vresilovic, Edward J.; Elliott, Dawn M.

2017-01-01

Tissue strain is an important indicator of mechanical function, but is difficult to noninvasively measure in the intervertebral disc. The objective of this study was to generate a disc strain template, a 3D average of disc strain, of a group of human L4–L5 discs loaded in axial compression. To do so, magnetic resonance images of uncompressed discs were used to create an average disc shape. Next, the strain tensors were calculated pixel-wise by using a previously developed registration algorithm. Individual disc strain tensor components were then transformed to the template space and averaged to create the disc strain template. The strain template reduced individual variability while highlighting group trends. For example, higher axial and circumferential strains were present in the lateral and posterolateral regions of the disc, which may lead to annular tears. This quantification of group-level trends in local 3D strain is a significant step forward in the study of disc biomechanics. These trends were compared to a finite element model that had been previously validated against the disc-level mechanical response. Depending on the strain component, 81–99% of the regions within the finite element model had calculated strains within one standard deviation of the template strain results. The template creation technique provides a new measurement technique useful for a wide range of studies, including more complex loading conditions, the effect of disc pathologies and degeneration, damage mechanisms, and design and evaluation of treatments. PMID:26694516

Qualitative and quantitative assessment of degeneration of cervical intervertebral discs and facet joints.

PubMed

Walraevens, Joris; Liu, Baoge; Meersschaert, Joke; Demaerel, Philippe; Delye, Hans; Depreitere, Bart; Vander Sloten, Jos; Goffin, Jan

2009-03-01

Degeneration of intervertebral discs and facet joints is one of the most frequently encountered spinal disorders. In order to describe and quantify degeneration and evaluate a possible relationship between degeneration and biomechanical parameters, e.g., the intervertebral range of motion and intradiscal pressure, a scoring system for degeneration is mandatory. However, few scoring systems for the assessment of degeneration of the cervical spine exist. Therefore, two separate objective scoring systems to qualitatively and quantitatively assess the degree of cervical intervertebral disc and facet joint degeneration were developed and validated. The scoring system for cervical disc degeneration consists of three variables which are individually scored on neutral lateral radiographs: "height loss" (0-4 points), "anterior osteophytes" (0-3 points) and "endplate sclerosis" (0-2 points). The scoring system for facet joint degeneration consists of four variables which are individually scored on neutral computed tomography scans: "hypertrophy" (0-2 points), "osteophytes" (0-1 point), "irregularity" on the articular surface (0-1 point) and "joint space narrowing" (0-1 point). Each variable contributes with varying importance to the overall degeneration score (max 9 points for the scoring system of cervical disc degeneration and max 5 points for facet joint degeneration). Degeneration of 20 discs and facet joints of 20 patients was blindly assessed by four raters: two neurosurgeons (one senior and one junior) and two radiologists (one senior and one junior), firstly based on first subjective impression and secondly using the scoring systems. Measurement errors and inter- and intra-rater agreement were determined. The measurement error of the scoring system for cervical disc degeneration was 11.1 versus 17.9% of the subjective impression results. This scoring system showed excellent intra-rater agreement (ICC = 0.86, 0.75-0.93) and excellent inter-rater agreement (ICC = 0.78, 0.64-0.88). Surgeons as well as radiologists and seniors as well as juniors obtained excellent inter- and intra-rater agreement. The measurement error of the scoring system for cervical facet joint degeneration was 20.1 versus 24.2% of the subjective impression results. This scoring system showed good intra-rater agreement (ICC = 0.71, 0.42-0.89) and fair inter-rater agreement (ICC = 0.49, 0.26-0.74). Both scoring systems fulfilled the criteria for recommendation proposed by Kettler and Wilke. Our scoring systems can be reliable and objective tools for assessing cervical disc and facet joint degeneration. Moreover, the scoring system of cervical disc degeneration was shown to be experience- and discipline-independent.

Sensitivity of MRI parameters within intervertebral discs to the severity of adolescent idiopathic scoliosis.

PubMed

Huber, Maxime; Gilbert, Guillaume; Roy, Julien; Parent, Stefan; Labelle, Hubert; Périé, Delphine

2016-11-01

To measure magnetic resonance imaging (MRI) parameters including relaxation times (T 1 ρ, T 2 ), magnetization transfer (MT) and diffusion parameters (mean diffusivity [MD], fractional anisotropy [FA]) of intervertebral discs in adolescents with idiopathic scoliosis, and to investigate the sensitivity of these MR parameters to the severity of the spine deformities. Thirteen patients with adolescent idiopathic scoliosis and three control volunteers with no history of spine disease underwent an MRI acquisition at 3T including the mapping of T 1 ρ, T 2 , MT, MD, and FA. The apical zone included all discs within the scoliotic curve while the control zone was composed of other discs. The severity was analyzed through low (<32°) versus high (>40°) Cobb angles. One-way analysis of variance (ANOVA) and agglomerative hierarchical clustering (AHC) were performed. Significant differences were found between the apical zone and the control zone for T 2 (P = 0.047), and between low and high Cobb angles for T 2 (P = 0.014) and MT (P = 0.002). AHC showed two distinct clusters, one with mainly low Cobb angles and one with mainly high Cobb angles, for the MRI parameters measured within the apical zone, with an accuracy of 0.9 and a Matthews correlation coefficient (MCC) of 0.8. Within the control zone, the AHC showed no clear classification (accuracy of 0.6 and MCC of 0.2). We successfully performed an in vivo multiparametric MRI investigation of young patients with adolescent idiopathic scoliosis. The MRI parameters measured within the intervertebral discs were found to be sensitive to intervertebral disc degeneration occurring with scoliosis and to the severity of scoliosis. J. Magn. Reson. Imaging 2016;44:1123-1131. © 2016 International Society for Magnetic Resonance in Medicine.

Morphometric analysis of the relationships between intervertebral disc and vertebral body heights: an anatomical and radiographic study of the human thoracic spine

PubMed Central

Kunkel, Maria E; Herkommer, Andrea; Reinehr, Michael; Böckers, Tobias M; Wilke, Hans-Joachim

2011-01-01

The main aim of this study was to provide anatomical data on the heights of the human intervertebral discs for all levels of the thoracic spine by direct and radiographic measurements. Additionally, the heights of the neighboring vertebral bodies were measured, and the prediction of the disc heights based only on the size of the vertebral bodies was investigated. The anterior (ADH), middle (MDH) and posterior heights (PDH) of the discs were measured directly and on radiographs of 72 spine segments from 30 donors (age 57.43 ± 11.27 years). The radiographic measurement error and the reliability of the measurements were calculated. Linear and non-linear regression analyses were employed for investigation of statistical correlations between the heights of the thoracic disc and vertebrae. Radiographic measurements displayed lower repeatability and were shorter than the anatomical ones (approximately 9% for ADH and 37% for PDH). The thickness of the discs varied from 4.5 to 7.2 mm, with the MDH approximately 22.7% greater. The disc heights showed good correlations with the vertebral body heights (R2, 0.659–0.835, P-values < 0.005; anova), allowing the generation of 10 prediction equations. New data on thoracic disc morphometry were provided in this study. The generated set of regression equations could be used to predict thoracic disc heights from radiographic measurement of the vertebral body height posterior. For the creation of parameterized models of the human thoracic discs, the use of the prediction equations could eliminate the need for direct measurement on intervertebral discs. Moreover, the error produced by radiographic measurements could be reduced at least for the PDH. PMID:21615399

Human body modeling method to simulate the biodynamic characteristics of spine in vivo with different sitting postures.

PubMed

Dong, Rui-Chun; Guo, Li-Xin

2017-11-01

The aim of this study is to model the computational model of seated whole human body including skeleton, muscle, viscera, ligament, intervertebral disc, and skin to predict effect of the factors (sitting postures, muscle and skin, buttocks, viscera, arms, gravity, and boundary conditions) on the biodynamic characteristics of spine. Two finite element models of seated whole body and a large number of finite element models of different ligamentous motion segments were developed and validated. Static, modal, and transient dynamic analyses were performed. The predicted vertical resonant frequency of seated body model was in the range of vertical natural frequency of 4 to 7 Hz. Muscle, buttocks, viscera, and the boundary conditions of buttocks have influence on the vertical resonant frequency of spine. Muscle played a very important role in biodynamic response of spine. Compared with the vertical posture, the posture of lean forward or backward led to an increase in stress on anterior or lateral posterior of lumbar intervertebral discs. This indicated that keeping correct posture could reduce the injury of vibration on lumbar intervertebral disc under whole-body vibration. The driving posture not only reduced the load of spine but also increased the resonant frequency of spine. Copyright © 2017 John Wiley & Sons, Ltd.

Precision of lumbar intervertebral measurements: does a computer-assisted technique improve reliability?

PubMed

Pearson, Adam M; Spratt, Kevin F; Genuario, James; McGough, William; Kosman, Katherine; Lurie, Jon; Sengupta, Dilip K

2011-04-01

Comparison of intra- and interobserver reliability of digitized manual and computer-assisted intervertebral motion measurements and classification of "instability." To determine if computer-assisted measurement of lumbar intervertebral motion on flexion-extension radiographs improves reliability compared with digitized manual measurements. Many studies have questioned the reliability of manual intervertebral measurements, although few have compared the reliability of computer-assisted and manual measurements on lumbar flexion-extension radiographs. Intervertebral rotation, anterior-posterior (AP) translation, and change in anterior and posterior disc height were measured with a digitized manual technique by three physicians and by three other observers using computer-assisted quantitative motion analysis (QMA) software. Each observer measured 30 sets of digital flexion-extension radiographs (L1-S1) twice. Shrout-Fleiss intraclass correlation coefficients for intra- and interobserver reliabilities were computed. The stability of each level was also classified (instability defined as >4 mm AP translation or 10° rotation), and the intra- and interobserver reliabilities of the two methods were compared using adjusted percent agreement (APA). Intraobserver reliability intraclass correlation coefficients were substantially higher for the QMA technique THAN the digitized manual technique across all measurements: rotation 0.997 versus 0.870, AP translation 0.959 versus 0.557, change in anterior disc height 0.962 versus 0.770, and change in posterior disc height 0.951 versus 0.283. The same pattern was observed for interobserver reliability (rotation 0.962 vs. 0.693, AP translation 0.862 vs. 0.151, change in anterior disc height 0.862 vs. 0.373, and change in posterior disc height 0.730 vs. 0.300). The QMA technique was also more reliable for the classification of "instability." Intraobserver APAs ranged from 87 to 97% for QMA versus 60% to 73% for digitized manual measurements, while interobserver APAs ranged from 91% to 96% for QMA versus 57% to 63% for digitized manual measurements. The use of QMA software substantially improved the reliability of lumbar intervertebral measurements and the classification of instability based on flexion-extension radiographs.

Nuclei pulposi formation from the embryonic notochord occurs normally in GDF-5-deficient mice.

PubMed

Maier, Jennifer A; Harfe, Brian D

2011-11-15

The transition of the mouse embryonic notochord into nuclei pulposi was determined ("fate mapped") in vivo in growth and differentiating factor-5 (GDF-5)-null mice using the Shhcre and R26R alleles. To determine whether abnormal nuclei pulposi formation from the embryonic notochord was responsible for defects present in adult nuclei pulposi of Gdf-5-null mice. The development, maintenance, and degeneration of the intervertebral disc are not understood. Previously, we demonstrated that all cells in the adult nucleus pulposus of normal mice are derived from the embryonic notochord. Gdf-5-null mice have been reported to contain intervertebral discs in which the nucleus pulposus is abnormal. It is currently unclear if disc defects in Gdf-5-null mice arise during the formation of nuclei pulposi from the notochord during embryogenesis or result from progressive postnatal degeneration of nuclei pulposi. Gdf-5 messenger RNA expression was examined in the discs of wild-type embryos by RNA in situ hybridization to determine when and where this gene was expressed. To examine nucleus pulposus formation in Gdf-5-null mice, intervertebral discs in which embryonic notochord cells were marked were analyzed in newborn and 24-week-old mice. Our Gdf-5 messenger RNA in situ experiments determined that this gene is localized to the annulus fibrosus and not the nucleus pulposus in mouse embryos. Notochord fate-mapping experiments revealed that notochord cells in Gdf-5-null mice correctly form nuclei pulposi. Our data suggest that the defects reported in the nucleus pulposus of adult Gdf-5-null mice do not result from abnormal patterning of the embryonic notochord. The use of mouse alleles to mark cells that produce all cell types that reside in the adult nucleus pulposus will allow for a detailed examination of disc formation in other mouse mutants that have been reported to contain disc defects.

Nuclei pulposi formation from the embryonic notochord occurs normally in GDF5-deficient mice

PubMed Central

Maier, Jennifer A.; Harfe, Brian D.

2011-01-01

Study Design The transition of the mouse embryonic notochord into nuclei pulposi was determined (“fate mapped”) in vivo in GDF-5 null mice using the Shhcre and R26R alleles. Objective To determine if abnormal nuclei pulposi formation from the embryonic notochord was responsible for defects present in adult nuclei pulposi of Gdf-5 null mice. Summary of Background Data The development, maintenance, and degeneration of the intervertebral disc are not understood. Previously, we demonstrated that all cells in the adult nucleus pulposus of normal mice are derived from the embryonic notochord. Gdf-5 null mice have been reported to contain intervertebral discs in which the nucleus pulposus is abnormal. It is currently unclear if disc defects in Gdf-5 null mice arise during the formation of nuclei pulposi from the notochord during embryogenesis or resulted from progressive postnatal degeneration of nuclei pulposi. Methods Gdf-5 mRNA expression was examined in the discs of wild-type embryos by RNA in situ hybridization to determine when and where this gene was expressed. To examine nucleus pulposus formation in Gdf-5 null mice, intervertebral discs in which embryonic notochord cells were marked were analyzed in newborn and 24 week old mice. Results Our Gdf-5 mRNA in situ experiments determined that this gene is localized to the annulus fibrosus and not the nucleus pulposus in mouse embryos. Notochord fate mapping experiments revealed that notochord cells in Gdf-5 null mice correctly form nuclei pulposi. Conclusion Our data suggest that the defects reported in the nucleus pulposus of adult Gdf-5 null mice do not result from abnormal patterning of the embryonic notochord. The use of mouse alleles to mark cells that produce all cell types that reside in the adult nucleus pulposus will allow for a detailed examination of disc formation in other mouse mutants that have been reported to contain disc defects. PMID:21278629

Physical inactivity is associated with narrower lumbar intervertebral discs, high fat content of paraspinal muscles and low back pain and disability.

PubMed

Teichtahl, Andrew J; Urquhart, Donna M; Wang, Yuanyuan; Wluka, Anita E; O'Sullivan, Richard; Jones, Graeme; Cicuttini, Flavia M

2015-05-07

Although physical inactivity has been associated with numerous chronic musculoskeletal complaints, few studies have examined its associations with spinal structures. Moreover, previously reported associations between physical activity and low back pain are conflicting. This study examined the associations between physical inactivity and intervertebral disc height, paraspinal fat content and low back pain and disability. Seventy-two community-based volunteers not selected for low back pain underwent magnetic resonance imaging (MRI) of their lumbosacral spine (L1 to S1) between 2011 and 2012. Physical activity was assessed between 2005 and 2008 by questionnaire, while low back pain and disability were assessed by the Chronic Pain Grade Scale at the time of MRI. Intervertebral disc height and cross-sectional area and fat content of multifidus and erector spinae were assessed from MRI. Lower physical activity levels were associated with a more narrow average intervertebral disc height (β -0.63 mm, 95% confidence interval (CI) -1.17 mm to -0.08 mm, P = 0.026) after adjusting for age, gender and body mass index (BMI). There were no significant associations between physical activity levels and the cross-sectional area of multifidus or erector spinae. Lower levels of physical activity were associated with an increased risk of high fat content in multifidus (odds ratio (OR) 2.7, 95% CI 1.1 to 6.7, P = 0.04) and high-intensity pain/disability (OR = 5.0, 95% CI 1.5 to 16.4, P = 0.008) after adjustment for age, gender and BMI. Physical inactivity is associated with narrower intervertebral discs, high fat content of the multifidus and high-intensity low back pain and disability in a dose-dependent manner among community-based adults. Longitudinal studies will help to determine the cause and effect nature of these associations.

[The assessment of the impact of rehabilitation on the pain intensity level in patients with herniated nucleus pulposus of the intervertebral disc].

PubMed

Koszela, Kamil; Krukowska, Sylwia; Woldańska-Okońska, Marta

2017-05-23

Back pain may be caused by many factors. In many cases it is difficult to unambiguously determine a cause of the pathology, which can involve various structures in the spine. In this paper we will discuss the symptoms associated with the degenerative changes of the intervertebral disc, which involve, among others, its bulging, dislocation and pressure on the surrounding structures. These problems require an adequate clinical and imaging diagnostics in order to implement an appropriate treatment. In the first place, it should be based on the conservative methods (such as: pharmacotherapy, rehabilitation and lifestyle changes). Only in the absence of improvement it is recommended to consider a surgical treatment. The aim of the study is to assess the impact of rehabilitation on the pain intensity level in patients with herniated nucleus pulposus of the intervertebral disc. The study was performed in 46 patients (age range: 19-85), including 26 women and 20 men. On the basis of imaging, all patients showed the presence of a slipped disc with disc herniation. The patients were treated conservatively. For pain assessment was used the The Laitinen Modified Questionnaire Indicators of Pain and The Visual- Analogue Scale. The results were statistically analyzed. The results clearly demonstrate the analgesic efficacy of specialized rehabilitation in the spinal pain syndrome in a discopathy with a spinal disc herniation of an intervertebral disc. The rehabilitation of patients with a back pain due to the presence of herniated nucleus pulposus has a significant analgesic effect. In the case of a presence of the herniated nucleus pulposus, the rehabilitation should be considered in a first place. If no improvement, a possible surgery should be considered. An important element of a conservative treatment is an effective rehabilitation, which is of vital economic importance, because a therapy including surgery usually requires subsequent rehabilitation and is much more expensive.

ISSLS prize winner: microstructure and mechanical disruption of the lumbar disc annulus: part II: how the annulus fails under hydrostatic pressure.

PubMed

Veres, Samuel P; Robertson, Peter A; Broom, Neil D

2008-12-01

Mechanically induced annular disruption of lumbar intervertebral discs followed by microstructural investigation. To investigate the role that elevated nuclear pressures play in disrupting the lumbar intervertebral disc's annulus fibrosus. Compound mechanical loadings have been used to recreate clinically relevant annular disruptions in vitro. However, the role that individual loading parameters play in disrupting the lumbar disc's annulus remains unclear. The nuclei of ovine lumbar intervertebral discs were gradually pressurized by injecting a viscous radio-opaque gel via their inferior vertebrae. Pressurization was conducted until catastrophic failure of the disc occurred. Investigation of the resulting annular disruption was carried out using microcomputed tomography and differential interference contrast microscopy. Gel extrusion from the posterior annulus was the most common mode of disc failure. Unlike other aspects of the annular wall, the posterior region was unable to distribute hydrostatic pressures circumferentially. In each extrusion case, severe disruption of the posterior annulus occurred. Although intralamellar disruption occurred in the mid annulus, interlamellar disruption occurred in the outer posterior annulus. Radial ruptures between lamellae always occurred in the mid-axial plane. With respect to the annular wall, the posterior region is most susceptible to failure in the presence of high nuclear pressure, even when loaded in the neutral position. Weak interlamellar cohesion of the outer posterior lamellae may explain why the majority of herniations remain contained as protrusions within the outer annular wall.

[HEART RHYTHM VARIABILITY ANALYSIS AND ASSESSMENT OF THE SPINAL PAIN SYNDROME DURING DRY IMMERSION].

PubMed

Sun, I; Voronkov, Yu I; Ardashev, V N; Glukhova, S I

2015-01-01

The spinal pain syndrome appears in cosmonauts on both short and long-duration missions. This untoward factor may affect body systems functioning and complicate the successful accomplishment of space mission. Purpose of the investigation was to examine the lumbar spine and to elucidate whether its condition relates to the spinal pain development and changes in heart rate variability (HRV) in the microgravity environment. The experiment was conducted in dry immersion as a method of microgravity effects simulation. It was shown that in dry immersion locomotion reproduces the patterns peculiar for significant gravitational unloading. Spinal pain intensity, angles and heights of the lumbar intervertebral discs and HRV were measured in 19 selected volunteers. During the experiment, all the volunteers developed pains in the back that abated gradually. Pain dependence on the height of intervertebral discs and cardiac regulatory mechanisms were investigated.

The role of the notochord in amniote vertebral column segmentation.

PubMed

Ward, Lizzy; Pang, Angel S W; Evans, Susan E; Stern, Claudio D

2018-07-01

The vertebral column is segmented, comprising an alternating series of vertebrae and intervertebral discs along the head-tail axis. The vertebrae and outer portion (annulus fibrosus) of the disc are derived from the sclerotome part of the somites, whereas the inner nucleus pulposus of the disc is derived from the notochord. Here we investigate the role of the notochord in vertebral patterning through a series of microsurgical experiments in chick embryos. Ablation of the notochord causes loss of segmentation of vertebral bodies and discs. However, the notochord cannot segment in the absence of the surrounding sclerotome. To test whether the notochord dictates sclerotome segmentation, we grafted an ectopic notochord. We find that the intrinsic segmentation of the sclerotome is dominant over any segmental information the notochord may possess, and no evidence that the chick notochord is intrinsically segmented. We propose that the segmental pattern of vertebral bodies and discs in chick is dictated by the sclerotome, which first signals to the notochord to ensure that the nucleus pulposus develops in register with the somite-derived annulus fibrosus. Later, the notochord is required for maintenance of sclerotome segmentation as the mature vertebral bodies and intervertebral discs form. These results highlight differences in vertebral development between amniotes and teleosts including zebrafish, where the notochord dictates the segmental pattern. The relative importance of the sclerotome and notochord in vertebral patterning has changed significantly during evolution. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Cartilage of the Intervertebral Disc Eng-Plate, A Histological, Histochemical, Fine Structure Study.

DTIC Science & Technology

1982-08-01

degeneration (Nachemson et al., 1970). These and related studies consider the end-plates to be composed of hyaline cartilage and thus homologues of articular...results of this study in rhesus indicate, that while present, the cartilage of the end-plate is quite different in structure and presumably...HZSTOLO6ZCAL,-ETCfU) I AUG 82 N 5 NUSSBAUM IUNCLASSIFDATRL8R-1222NL.rnximommmB~iIEND2 AFAMRL-TR-81 - 122 " CARTILAGE OF THE INTERVERTEBRAL DISC END-PLATE A

Intervertebral disc space infection caused by Aspergillus fumigatus.

PubMed

Lang, E W; Pitts, L H

1996-01-01

The authors describe the case of a 53-year-old woman who suffered from an Aspergillus fumigatus infection of the L2/3 intervertebral disc space unrelated to previous operations on her lumbar spine. After surgical debridement combined with amphotericin therapy she died on the 23rd postoperative day from a fulminant bacterial sepsis of pulmonary origin. Although she had intermittently used steroids for bronchial asthma, this is an unusual case of fungal infection of the lumbar spine in an apparently immunocompetent patient.

Mild (not severe) disc degeneration is implicated in the progression of bilateral L5 spondylolysis to spondylolisthesis.

PubMed

Ramakrishna, Vivek A S; Chamoli, Uphar; Viglione, Luke L; Tsafnat, Naomi; Diwan, Ashish D

2018-04-02

Spondylolytic (or lytic) spondylolisthesis is often associated with disc degeneration at the index-level; however, it is not clear if disc degeneration is the cause or the consequence of lytic spondylolisthesis. The main objective of this computed tomography based finite element modelling study was to examine the role of different grades of disc degeneration in the progression of a bilateral L5-lytic defect to spondylolisthesis. High-resolution computed tomography data of the lumbosacral spine from an anonymised healthy male subject (26 years old) were segmented to build a 3D-computational model of an INTACT L1-S1 spine. The INTACT model was manipulated to generate four more models representing a bilateral L5-lytic defect and the following states of the L5-S1 disc: nil degeneration (NOR LYTIC), mild degeneration (M-DEG LYTIC), mild degeneration with 50% disc height collapse (M-DEG-COL LYTIC), and severe degeneration with 50% disc height collapse(S-COL LYTIC). The models were imported into a finite element modelling software for pre-processing, running nonlinear-static solves, and post-processing of the results. Compared with the baseline INTACT model, M-DEG LYTIC model experienced the greatest increase in kinematics (Fx range of motion: 73% ↑, Fx intervertebral translation: 53%↑), shear stresses in the annulus (Fx anteroposterior: 163%↑, Fx posteroanterior: 31%↑), and strain in the iliolumbar ligament (Fx: 90%↑). The S-COL LYTIC model experienced a decrease in mobility (Fx range of motion: 48%↓, Fx intervertebral translation: 69%↓) and an increase in normal stresses in the annulus (Fx Tensile: 170%↑; Fx Compressive: 397%↑). No significant difference in results was noted between M-DEG-COL LYTIC and S-COL LYTIC models. In the presence of a bilateral L5 spondylolytic defect, a mildly degenerate index-level disc experienced greater intervertebral motions and shear stresses compared with a severely degenerate index-level disc in flexion and extension bending motions. Disc height collapse, with or without degenerative changes in the stiffness properties of the disc, is one of the plausible re-stabilisation mechanisms available to the L5-S1 motion segment to mitigate increased intervertebral motions and shear stresses due to a bilateral L5 lytic defect.

Chemonucleolysis for relief of sciatica due to a herniated intervertebral disc.

PubMed Central

McCulloch, J A

1981-01-01

Chemonucleolysis is the nonoperative chemical removal of displaced lumbar disc material. The enzyme chymopapain, which has a wide margin of safety between its effective therapeutic and toxic doses, is effective in the management of sciatica due to a herniated intervertebral disc. The patient will have leg pain as the dominant symptom and a 50% reduction in straight-leg raising with or without bowstring discomfort and crossover pain. Neurologic symptoms and signs are usual, as are abnormal results of contrast studies, which will verify the level of involvement. In 220 randomly selected patients who met criteria for the diagnosis of sciatica due to a herniated intervertebral disc and did not have psychogenic or nonorganic spinal pain, a spinal stenosis or a history of a previous, unsuccessful operation to relieve the sciatica, chemonucleolysis had a success rate of 80%. The only complications were a severe anaphylactic reaction in two patients and lesser, delayed reactions in five others. All of the reactions were successfully treated. Of the 45 patients in whom chemonucleolysis was unsuccessful, 38 underwent a laminectomy. In 3 of the 38 the results of chemonucleolysis were initially good, but later the disc herniation recurred; thus, the long-term treatment failure rate was 1.4%. PMID:7011530

Frequency response of pig intervertebral disc cells subjected to dynamic hydrostatic pressure.

PubMed

Kasra, Mehran; Merryman, W David; Loveless, Kristen N; Goel, Vijay K; Martin, James D; Buckwalter, Joseph A

2006-10-01

The pathogenesis of vibration-induced disorders of intervertebral disc at the cellular level is largely unknown. Dynamic loads with frequencies close to that of the in vivo human spine resonant frequency (4-6 Hz) have a destructive effect, which may induce extracellular disc matrix (ECM) degradation. To investigate this issue, three-dimensional (3D) alginate cultures of normal pig intervertebral disc nucleus and inner annulus cells were tested under dynamic hydrostatic loading. Alginate cultures of each region were divided into six groups; five groups were exposed to cyclic hydrostatic pressures of frequencies 1, 3, 5, 8, and 10 Hz with the same amplitude (1 MPa), and group 6 was the control group (no loading). Cultures of different groups were loaded for 3 days (30 min daily) in a hydraulic chamber. Effects of loading frequency on disc collagen and protein metabolism were investigated by measuring 3H-proline-labeled proteins associated with the cells in the extracellular matrix and release of 3H-proline-labeled molecules into culture medium. The results indicated a poor synthesis rate and more degradation near the 5 Hz frequency. The repeatability of experiments was verified by performing two experiments with the same protocol. Both experiments indicated that a threshold frequency of around 5 Hz disrupted protein metabolism. Copyright (c) 2006 Orthopaedic Research Society.

Low rate loading-induced convection enhances net transport into the intervertebral disc in vivo.

PubMed

Gullbrand, Sarah E; Peterson, Joshua; Mastropolo, Rosemarie; Roberts, Timothy T; Lawrence, James P; Glennon, Joseph C; DiRisio, Darryl J; Ledet, Eric H

2015-05-01

The intervertebral disc primarily relies on trans-endplate diffusion for the uptake of nutrients and the clearance of byproducts. In degenerative discs, diffusion is often diminished by endplate sclerosis and reduced proteoglycan content. Mechanical loading-induced convection has the potential to augment diffusion and enhance net transport into the disc. The ability of convection to augment disc transport is controversial and has not been demonstrated in vivo. To determine if loading-induced convection can enhance small molecule transport into the intervertebral disc in vivo. Net transport was quantified via postcontrast enhanced magnetic resonance imaging (MRI) into the discs of the New Zealand white rabbit lumbar spine subjected to in vivo cyclic low rate loading. Animals were administered the MRI contrast agent gadodiamide intravenously and subjected to in vivo low rate loading (0.5 Hz, 200 N) via a custom external loading apparatus for either 2.5, 5, 10, 15, or 20 minutes. Animals were then euthanized and the lumbar spines imaged using postcontrast enhanced MRI. The T1 constants in the nucleus, annulus, and cartilage endplates were quantified as a measure of gadodiamide transport into the loaded discs compared with the adjacent unloaded discs. Microcomputed tomography was used to quantify subchondral bone density. Low rate loading caused the rapid uptake and clearance of gadodiamide in the nucleus compared with unloaded discs, which exhibited a slower rate of uptake. Relative to unloaded discs, low rate loading caused a maximum increase in transport into the nucleus of 16.8% after 5 minutes of loading. Low rate loading increased the concentration of gadodiamide in the cartilage endplates at each time point compared with unloaded levels. Results from this study indicate that forced convection accelerated small molecule uptake and clearance in the disc induced by low rate mechanical loading. Low rate loading may, therefore, be therapeutic to the disc as it may enhance the nutrient uptake and waste product clearance. Copyright © 2015 Elsevier Inc. All rights reserved.

Thoracic myelopathy with alkaptonuria.

PubMed

Akeda, Koji; Kasai, Yuichi; Kawakita, Eiji; Matsumura, Yoshihiro; Kono, Toshibumi; Murata, Tetsuya; Uchida, Atsumasa

2008-01-15

A case of thoracic myelopathy with alkaptonuria (ochronotic spondyloarthropathy) is presented. To present and review the first reported case of an alkaptonuric patient with concomitant thoracic myelopathy. Alkaptonuria, a rare hereditary metabolic disease, is characterized by accumulation of homogentistic acid, ochronosis, and destruction of connective tissue resulting in degenerative spondylosis and arthritis. Despite the high incidence of intervertebral disc diseases among patients with alkaptonuria, neurologic symptoms caused by spinal disease are rare. Thoracic myelopathy in a patient with alkaptonuria has not been previously reported. The clinical course, radiologic features, pathology, and treatment outcome of an alkaptonuria patient with thoracic myelopathy was documented. Myelopathy of the patient was caused by rupture of a thoracic intervertebral disc. The neurologic symptoms of the patient were markedly improved after surgery. We have reported for the first time, that an alkaptonuria patient showed thoracic myelopathy caused by rupture of a thoracic intervertebral disc. Decompression followed by the instrumented fusion of the thoracic spine was effective for improving the neurologic symptoms.

Evaluation of Electrospun Nanofiber-Anchored Silicone for the Degenerative Intervertebral Disc

PubMed Central

Riahanizad, S.

2017-01-01

The nucleus pulposus (NP) substitution by polymeric gel is one of the promising techniques for the repair of the degenerative intervertebral disc (IVD). Silicone gel is one of the potential candidates for a NP replacement material. Electrospun fiber anchorage to silicone disc, referred as ENAS disc, may not only improve the biomechanical performances of the gel but it can also improve restoration capability of the gel, which is unknown. This study successfully produced a novel process to anchor any size and shape of NP gel with electrospun fiber mesh. Viscoelastic properties of silicone and ENAS disc were measured using standard experimental techniques and compared with the native tissue properties. Ex vivo mechanical tests were conducted on ENAS disc-implanted rabbit tails to the compare the mechanical stability between intact and ENAS implanted spines. This study found that viscoelastic properties of ENAS disc are higher than silicone disc and comparable to the viscoelastic properties of human NP. The ex vivo studies found that the ENAS disc restore the mechanical functionality of rabbit tail spine, after discectomy of native NP and replacing the NP by ENAS disc. Therefore, the PCL ENF mesh anchoring technique to a NP implant can have clinical potential. PMID:29181144

Difference in Energy Metabolism of Annulus Fibrosus and Nucleus Pulposus Cells of the Intervertebral Disc

PubMed Central

Salvatierra, Jessica Czamanski; Yuan, Tai Yi; Fernando, Hanan; Castillo, Andre; Gu, Wei Yong; Cheung, Herman S.; Huant, C.-Y. Charles

2011-01-01

Low back pain is associated with intervertebral disc degeneration. One of the main signs of degeneration is the inability to maintain extracellular matrix integrity. Extracellular matrix synthesis is closely related to production of adenosine triphosphate (i.e. energy) of the cells. The intervertebral disc is composed of two major anatomical regions: annulus fibrosus and nucleus pulposus, which are structurally and compositionally different, indicating that their cellular metabolisms may also be distinct. The objective of this study was to investigate energy metabolism of annulus fibrosus and nucleus pulposus cells with and without dynamic compression, and examine differences between the two cell types. Porcine annulus and nucleus tissues were harvested and enzymatically digested. Cells were isolated and embedded into agarose constructs. Dynamically loaded samples were subjected to a sinusoidal displacement at 2 Hz and 15% strain for 4 h. Energy metabolism of cells was analyzed by measuring adenosine triphosphate content and release, glucose consumption, and lactate/nitric oxide production. A comparison of those measurements between annulus and nucleus cells was conducted. Annulus and nucleus cells exhibited different metabolic pathways. Nucleus cells had higher adenosine triphosphate content with and without dynamic loading, while annulus cells had higher lactate production and glucose consumption. Compression increased adenosine triphosphate release from both cell types and increased energy production of annulus cells. Dynamic loading affected energy metabolism of intervertebral disc cells, with the effect being greater in annulus cells. PMID:21625336

Cost-benefit value of microscopic examination of intervertebral discs.

PubMed

Grzybicki, D M; Callaghan, E J; Raab, S S

1998-09-01

Given the virtual absence of histologically detected, clinically unsuspected disease in intervertebral disc specimens, some authors have advocated that histological examination be discontinued. However, the examination of intervertebral disc specimens remains common practice in most pathology laboratories. No cost-benefit analysis of this practice has been made; therefore, the authors' goal in this study was perform such an analysis. Using the University of Iowa surgical pathology database, 1109 patients who had undergone a laminectomy were identified retrospectively. These cases were classified into four categories based on the patients' preoperative clinical diagnosis and final histopathological diagnosis: insignificant clinical diagnosis/insignificant pathological diagnosis (ICIP), significant clinical diagnosis/insignificant pathological diagnosis (SCIP), significant clinical diagnosis/significant pathological diagnosis (SCSP), and insignificant clinical diagnosis/significant pathological diagnosis (ICSP). A significant clinical diagnosis was defined as one other than a benign, noninfectious indication for laminectomy. A significant pathological diagnosis was a diagnosis other than degenerative changes. The cost-benefit value of performing a histological examination in cases with significant or insignificant clinical diagnoses was examined. The cases were classified as: 1068 ICIP, 17 SCIP, 21 SCSP, and three ICSP. On chart review, in all three cases of ICSP an epidural abscess was identified perioperatively and the subsequent histological diagnosis did not affect patient care. The costs per case of identifying a significant pathological diagnosis with a significant and an insignificant clinical diagnosis were $44.79 and $8811, respectively. Histological examination of intervertebral disc specimens is cost beneficial only if there is a significant preoperative clinical diagnosis.

Mechanical Vibrations Reduce the Intervertebral Disc Swelling and Muscle Atrophy from Bed Rest

NASA Technical Reports Server (NTRS)

Holguin, Nilsson; Muir, Jesse; Evans, Harlan J.; Qin, Yi-Xian; Rubin, Clinton; Wagshul, Mark; Judex, Stefan

2007-01-01

Loss of functional weight bearing, such as experienced during space flight or bed rest (BR), distorts intervertebral disc (IVD) and muscle morphology. IVDs are avascular structures consisting of cells that may derive their nutrition and waste removal from the load induced fluid flow into and out of the disc. A diurnal cycle is produced by forces related to weight bearing and muscular activity, and comprised of a supine and erect posture over a 24 hr period. A diurnal cycle will include a disc volume change of approx. 10-13%. However, in space there are little or no diurnal changes because of the microgravity, which removes the gravitational load and compressive forces to the back muscles. The BR model and the etiology of the disc swelling and muscle atrophy could provide insight into those subjects confined to bed for chronic disease/injury and aging. We hypothesize that extremely low-magnitude, high frequency mechanical vibrations will abate the disc degeneration and muscle loss associated with long-term BR.

Slow deformation of intervertebral discs.

PubMed

Broberg, K B

1993-01-01

Intervertebral discs exhibit pronounced time-dependent deformations when subjected to load variations. These deformations are caused by fluid flow to and from the disc and by viscoelastic deformation of annulus fibres. The fluid flow is caused by differences between mechanical and osmotic pressure. A mechanical model of lumbar disc functions allows one to calculate both the extent of fluid flow and its implications for disc height as well as the role played by viscoelastic deformation of annulus fibres. From such calculations changes in body height are estimated. Experimental results already documented in the literature offer bases for the determination of the parameters involved. Body height variations are studied, both those related to normal diurnal rhythmicity and those related to somewhat exceptional circumstances. The normal diurnal fluid flow is found to be about +/- 40% of the disc fluid content late in the evening. Viscoelastic deformation of annulus fibres contributes approximately one quarter of the height change obtained after several hours normal activity, but dominates during the first hour.

Prognosis of intervertebral disc loss from diagnosis of degenerative disc disease

NASA Astrophysics Data System (ADS)

Li, S.; Lin, A.; Tay, K.; Romano, W.; Osman, Said

2015-03-01

Degenerative Disc Disease (DDD) is one of the most common causes of low back pain, and is a major factor in limiting the quality of life of an individual usually as they enter older stages of life, the disc degeneration reduces the shock absorption available which in turn causes pain. Disc loss is one of the central processes in the pathogenesis of DDD. In this study, we investigated whether the image texture features quantified from magnetic resonance imaging (MRI) could be appropriate markers for diagnosis of DDD and prognosis of inter-vertebral disc loss. The main objective is to use simple image based biomarkers to perform prognosis of spinal diseases using non-invasive procedures. Our results from 65 subjects proved the higher success rates of the combination marker compared to the individual markers and in the future, we will extend the study to other spine regions to allow prognosis and diagnosis of DDD for a wider region.

Lumbar spine intervertebral disc gene delivery: a pilot study in lewis rats.

PubMed

Damle, Sheela R; Rawlins, Bernard A; Boachie-Adjei, Oheneba; Crystal, Ronald G; Hidaka, Chisa; Cunningham, Matthew E

2013-02-01

Basic research toward understanding and treating disc pathology in the spine has utilized numerous animal models, with delivery of small molecules, purified factors, and genes of interest. To date, gene delivery to the rat lumbar spine has only been described utilizing genetically programmed cells in a matrix which has required partial disc excision, and expected limitation of treatment diffusion into the disc. This study was designed to develop and describe a surgical technique for lumbar spine exposure and disc space preparation, and use of a matrix-free method for gene delivery. Naïve or genetically programmed isogeneic bone marrow stromal cells were surgically delivered to adolescent male Lewis rat lumbar discs, and utilizing quantitative biochemical and qualitative immunohistological assessments, the implanted cells were detected 3 days post-procedure. Statistically significant differences were noted for recovery of the β-galactosidase marker gene comparing delivery of naïve or labeled cells (10(5) cells per disc) from the site of implantation, and between delivery of 10(5) or 10(6) labeled cells per disc at the site of implantation and the adjacent vertebral body. Immunohistology confirmed that the β-galactosidase marker was detected in the adjacent vertebra bone in the zone of surgical implantation. The model requires further testing in larger cohorts and with biologically active genes of interest, but the observations from the pilot experiments are very encouraging that this will be a useful comparative model for basic spine research involving gene or cell delivery, or other locally delivered therapies to the intervertebral disc or adjacent vertebral bodies in rats.

Fibrotic-like changes in degenerate human intervertebral discs revealed by quantitative proteomic analysis.

PubMed

Yee, A; Lam, M P Y; Tam, V; Chan, W C W; Chu, I K; Cheah, K S E; Cheung, K M C; Chan, D

2016-03-01

Intervertebral disc degeneration (IDD) can lead to symptomatic conditions including sciatica and back pain. The purpose of this study is to understand the extracellular matrix (ECM) changes in disc biology through comparative proteomic analysis of degenerated and non-degenerated human intervertebral disc (IVD) tissues of different ages. Seven non-degenerated (11-46 years of age) and seven degenerated (16-53 years of age) annulus fibrosus (AF) and nucleus pulposus (NP) samples were used. Proteins were extracted using guanidine hydrochloride, separated from large proteoglycans (PGs) by caesium chloride (CsCl) density gradient ultracentrifugation, and identified using liquid chromatography (LC) coupled with tandem mass spectrometry (MS/MS). For quantitative comparison, proteins were labeled with iTRAQ reagents. Collagen fibrils in the NP were assessed using scanning electron microscopy (SEM). In the AF, quantitative analysis revealed increased levels of HTRA1, COMP and CILP in degeneration when compared with samples from older individuals. Fibronectin showed increment with age and degeneration. In the NP, more CILP and CILP2 were present in degenerated samples of younger individuals. Reduced protein solubility was observed in degenerated and older non-degenerated samples correlated with an accumulation of type I collagen in the insoluble fibers. Characterization of collagen fibrils in the NP revealed smaller mean fibril diameters and decreased porosity in the degenerated samples. Our study identified distinct matrix changes associated with aging and degeneration in the intervertebral discs (IVDs). The nature of the ECM changes, together with observed decreased in solubility and changes in fibril diameter is consistent with a fibrotic-like environment. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

The Effects of Physiological Biomechanical Loading on Intradiscal Pressure and Annulus Stress in Lumbar Spine: A Finite Element Analysis

PubMed Central

Zahari, Siti Nurfaezah; Rahim, Nor Raihanah Abdull; Kamarul, Tunku

2017-01-01

The present study was conducted to examine the effects of body weight on intradiscal pressure (IDP) and annulus stress of intervertebral discs at lumbar spine. Three-dimensional finite element model of osseoligamentous lumbar spine was developed subjected to follower load of 500 N, 800 N, and 1200 N which represent the loads for individuals who are normal and overweight with the pure moments at 7.5 Nm in flexion and extension motions. It was observed that the maximum IDP was 1.26 MPa at L1-L2 vertebral segment. However, the highest increment of IDP was found at L4-L5 segment where the IDP was increased to 30% in flexion and it was more severe at extension motion reaching to 80%. Furthermore, the maximum annulus stress also occurred at the L1-L2 segment with 3.9 MPa in extension motion. However, the highest increment was also found at L4-L5 where the annulus stress increased to 17% in extension motion. Based on these results, the increase of physiological loading could be an important factor to the increment of intradiscal pressure and annulus fibrosis stress at all intervertebral discs at the lumbar spine which may lead to early intervertebral disc damage. PMID:29065672

The Effects of Physiological Biomechanical Loading on Intradiscal Pressure and Annulus Stress in Lumbar Spine: A Finite Element Analysis.

PubMed

Zahari, Siti Nurfaezah; Latif, Mohd Juzaila Abd; Rahim, Nor Raihanah Abdull; Kadir, Mohammed Rafiq Abdul; Kamarul, Tunku

2017-01-01

The present study was conducted to examine the effects of body weight on intradiscal pressure (IDP) and annulus stress of intervertebral discs at lumbar spine. Three-dimensional finite element model of osseoligamentous lumbar spine was developed subjected to follower load of 500 N, 800 N, and 1200 N which represent the loads for individuals who are normal and overweight with the pure moments at 7.5 Nm in flexion and extension motions. It was observed that the maximum IDP was 1.26 MPa at L1-L2 vertebral segment. However, the highest increment of IDP was found at L4-L5 segment where the IDP was increased to 30% in flexion and it was more severe at extension motion reaching to 80%. Furthermore, the maximum annulus stress also occurred at the L1-L2 segment with 3.9 MPa in extension motion. However, the highest increment was also found at L4-L5 where the annulus stress increased to 17% in extension motion. Based on these results, the increase of physiological loading could be an important factor to the increment of intradiscal pressure and annulus fibrosis stress at all intervertebral discs at the lumbar spine which may lead to early intervertebral disc damage.

Can Exercise Positively Influence the Intervertebral Disc?

PubMed

Belavý, Daniel L; Albracht, Kirsten; Bruggemann, Gert-Peter; Vergroesen, Pieter-Paul A; van Dieën, Jaap H

2016-04-01

To better understand what kinds of sports and exercise could be beneficial for the intervertebral disc (IVD), we performed a review to synthesise the literature on IVD adaptation with loading and exercise. The state of the literature did not permit a systematic review; therefore, we performed a narrative review. The majority of the available data come from cell or whole-disc loading models and animal exercise models. However, some studies have examined the impact of specific sports on IVD degeneration in humans and acute exercise on disc size. Based on the data available in the literature, loading types that are likely beneficial to the IVD are dynamic, axial, at slow to moderate movement speeds, and of a magnitude experienced in walking and jogging. Static loading, torsional loading, flexion with compression, rapid loading, high-impact loading and explosive tasks are likely detrimental for the IVD. Reduced physical activity and disuse appear to be detrimental for the IVD. We also consider the impact of genetics and the likelihood of a 'critical period' for the effect of exercise in IVD development. The current review summarises the literature to increase awareness amongst exercise, rehabilitation and ergonomic professionals regarding IVD health and provides recommendations on future directions in research.

Measurement of lumbar spine intervertebral motion in the sagittal plane using videofluoroscopy.

PubMed

Harvey, Steven; Hukins, David; Smith, Francis; Wardlaw, Douglas; Kader, Deiary

2016-08-10

Static radiographic techniques are unable to capture the wealth of kinematic information available from lumbar spine sagittal plane motion. Demonstration of a viable non-invasive technique for acquiring and quantifying intervertebral motion of the lumbar spine in the sagittal plane. Videofluoroscopic footage of sagittal plane lumbar spine flexion-extension in seven symptomatic volunteers (mean age = 48 yrs) and one asymptomatic volunteer (age = 54 yrs) was recorded. Vertebral bodies were digitised using customised software employing a novel vertebral digitisation scheme that was minimally affected by out-of-plane motion. Measurement errors in intervertebral rotation (± 1°) and intervertebral displacement (± 0.5 mm) compare favourably with the work of others. Some subjects presenting with an identical condition (disc prolapse) exhibited a similar column vertebral flexion-extension relative to S1 (L3: max. 5.9°, min. 5.6°), while in others (degenerative disc disease) there was paradoxically a significant variation in this measurement (L3: max. 28.1°, min. 0.7°). By means of a novel vertebral digitisation scheme and customised digitisation/analysis software, sagittal plane intervertebral motion data of the lumbar spine data has been successfully extracted from videofluoroscopic image sequences. Whilst the intervertebral motion signatures of subjects in this study differed significantly, the available sample size precluded the inference of any clinical trends.

Molecular regulation of CCN2 in the intervertebral disc: lessons learned from other connective tissues.

PubMed

Tran, Cassie M; Shapiro, Irving M; Risbud, Makarand V

2013-08-08

Connective tissue growth factor (CCN2/CTGF) plays an important role in extracellular matrix synthesis, especially in skeletal tissues such as cartilage, bone, and the intervertebral disc. As a result there is a growing interest in examining the function and regulation of this important molecule in the disc. This review discusses the regulation of CCN2 by TGF-β and hypoxia, two critical determinants that characterize the disc microenvironment, and discusses known functions of CCN2 in the disc. The almost ubiquitous regulation of CCN2 by TGF-β, including that seen in the disc, emphasizes the importance of the TGF-β-CCN2 relationship, especially in terms of extracellular matrix synthesis. Likewise, the unique cross-talk between CCN2 and HIF-1 in the disc highlights the tissue and niche specific mode of regulation. Taken together the current literature supports an anabolic role for CCN2 in the disc and its involvement in the maintenance of tissue homeostasis during both health and disease. Further studies of CCN2 in this tissue may reveal valuable targets for the biological therapy of disc degeneration. © 2013 Elsevier B.V. All rights reserved.

Effect of dynamic hydrostatic pressure on rabbit intervertebral disc cells.

PubMed

Kasra, Mehran; Goel, Vijay; Martin, James; Wang, Shea-Tien; Choi, Woosung; Buckwalter, Joseph

2003-07-01

The pathogenesis of vibration-induced disorders of intervertebral disc at the cellular level is largely unknown. The objective of this study was to establish a method to investigate the ranges of constructive and destructive hydrostatic loading frequencies and amplitudes in preventing or inducing extracellular disc matrix degradation. Using a hydraulic chamber, normal rabbit intervertebral disc cells were tested under dynamic hydrostatic loading. Monolayer cultures of disc outer annulus cells and 3-dimensional (3-D) alginate cultures of disc nucleus pulposus cells were tested. Effects of different loading amplitudes (3-D culture, 0-3 MPa; monolayer, 0-1.7 MPa) and frequencies (1-20 Hz) on disc collagen and protein metabolism were investigated by measuring 3H-proline-labeled proteins associated with the cells in the extracellular matrix and release of 3H-proline-labeled molecules into culture medium. High frequency and high amplitude hydrostatic stress stimulated collagen synthesis in cultures of outer annulus cells whereas the lower amplitude and frequency hydrostatic stress had little effect. For the same loading duration and repetition, neither treatment significantly affected the relative amount of protein released from the cell layers, indicating that protein degradation and stability were unaffected. In the 3-D nucleus culture, higher amplitude and frequency increased synthesis rate and lowered degradation. In this case, loading amplitude had a stronger influence on cell response than that of loading frequency. Considering the ranges of loading amplitude and frequency used in this study, short-term application of high loading amplitudes and frequencies was beneficial in stimulation of protein synthesis and reduction of protein degradation.

The multidirectional bending properties of the human lumbar intervertebral disc.

PubMed

Spenciner, David; Greene, David; Paiva, James; Palumbo, Mark; Crisco, Joseph

2006-01-01

While the biomechanical properties of the isolated intervertebral disc have been well studied in the three principal anatomic directions of flexion/extension, axial rotation, and lateral bending, there is little data on the properties in the more functional directions that are combinations of these principal anatomic directions. To determine the bending flexibility, range of motion (ROM), and neutral zone (NZ) of the human lumbar disc in multiple directions and to determine if the values about the combined moment axes can be predicted from the values about principal moment axes. Three-dimensional biomechanical analysis of the elastic bending properties of human lumbar discs about principal and combined moment axes. Pure, unconstrained moments were applied about multiple axes. The bending properties (flexibility, ROM, and NZ) of isolated lumbar discs (n=4 for L2/L3 and n=3 for L4/L5) were determined in the six principal directions and in 20 combined directions. The experimental values were compared with those predicted from the linear combination of the six principal moment axes. The maximum and minimum values of the biomechanical properties were found at the principal moment axes. Among combined moment axes, ROM and NZ (but not flexibility) values were predicted from the principal moment axis values. The principal moment axes coincide with the primary mechanical axes of the intervertebral disc and demonstrate significant differences in direction for values of flexibility, ROM, and NZ. Not all combined moment axis values can be predicted from principal moment axis values.

Intervertebral disc adaptation to wedging deformation.

PubMed

Stokes, Ian A F; Aronsson, David D; Clark, Katherine C; Roemhildt, Maria L

2006-01-01

Although scoliosis includes wedge deformities of both vertebrae and discs, little is known about the causes of the discal changes, and whether they result from mechanical influences on growth and/or remodelling. An external apparatus attached to transvertebral pins applied compression and 15 degrees of angulation to each of two adjacent young rat caudal intervertebral discs for 5 weeks (four animals), or for 10 weeks (four animals). Each week, micro-CT scanning documented the in vivo discal wedging. After euthanasia, tail segments (three vertebrae and the 2 angulated discs) were excised and their flexibility was measured over a range of lateral bending. The angle of maximum flexibility was recorded. Then discs were fixed in situ (with the external apparatus in place) and sectioned for polarized light microscopy. The disc-wedging deformity averaged 15 degrees initially, it averaged 20 degrees after 5 weeks, and then reduced to 10 degrees (in 10 week animals). The lateral bending flexibility showed a distinct maximum at an average of 1.1 degrees from the in vivo position in the 5-week animals, indicating structural remodeling of the discs almost to the deformed geometry. The 10-week animals had maximum flexibility at 1.4 degrees from the in vivo position (no significant difference between 5 and 10-week animals.) Collagen crimp angles [Cassidy et al., Conn Tiss Res 1989, 23:75-88] were not significantly different between convex and concave sides, again suggesting that remodeling had occurred. In a mechanically induced scoliosis deformity in skeletally immature rats, the intervertebral discs underwent remodeling within 5 weeks. This indicates that this animal model is suitable for studying adaptive wedging changes in human scoliosis.

Asymmetrical and smaller size of trunk muscles in combat sports athletes with lumbar intervertebral disc degeneration.

PubMed

Iwai, Kazunori; Koyama, Koji; Okada, Takashi; Nakazato, Koichi; Takahashi, Ray; Matsumoto, Shingo; Yamamoto, Yosuke; Hiranuma, Kenji

2016-01-01

Lumbar intervertebral disc degeneration (LDD) frequently occurs in athletes. Associations between LDD and trunk muscles still remain unclear. This study examined whether there is an association between the prevalence of LDD and the symmetry and size of the cross-sectional areas (CSAs) of the trunk muscles in combat sports athletes. Participants in this study were 151 collegiate male combat sports athletes. A total of 755 lumbar intervertebral discs from L1-2 to L5-S1 in 151 athletes were assessed using magnetic resonance imaging (MRI) and a comprehensive grading system of LDD (grades I-V). All 151 athletes were divided into 2 groups: LDD and non-LDD. CSAs of trunk muscles at the L3-4 disc level were measured using MRI. Sixty-nine athletes had LDD at 1 or more disc levels (45.7 %). The LDD grade for the lower 2 disc levels was significantly higher than that for the other disc levels (p < 0.001). The CSAs of the left and right sides in trunk muscles were significantly asymmetrical, independent of the LDD which was prevalent in the disc levels (obliques: p = 0.040; quadratus lumborum: p < 0.001). The relative CSAs of trunk muscles to their body weight in the LDD group were significantly smaller than those in the non-LDD group (rectus abdominis: p = 0.011; obliques: p = 0.024; quadratus lumborum: p = 0.006; lumbar erector spinae plus multifidus: p = 0.001). This study suggests that the prevalence of LDD is associated with asymmetrical and relatively smaller CSAs of trunk muscles in combat sports athletes.

A preliminary in vitro study into the use of IL-1Ra gene therapy for the inhibition of intervertebral disc degeneration

PubMed Central

Le Maitre, Christine L; Freemont, Anthony J; Hoyland, Judith A

2006-01-01

Conventional therapies for low back pain (LBP) are purely symptomatic and do not target the cause of LBP, which in approximately 40% of cases is caused by degeneration of the intervertebral disc (DIVD). Targeting therapies to inhibit the process of degeneration would be a potentially valuable treatment for LBP. There is increasing evidence for a role for IL-1 in DIVD. A natural inhibitor of IL-1 exists, IL-1Ra, which would be an ideal molecular target for inhibiting IL-1-mediated effects involved in DIVD and LBP. In this study, the feasibility of ex vivo gene transfer of IL-1Ra to the IVD was investigated. Monolayer and alginate cultures of normal and degenerate human intervertebral disc (IVD) cells were infected with an adenoviral vector carrying the IL-1Ra gene (Ad-IL-1Ra) and protein production measured using an enzyme-linked immunosorbent assay. The ability of these infected cells to inhibit the effects of IL-1 was also investigated. In addition, normal and degenerate IVD cells infected with Ad-IL-1Ra were injected into degenerate disc tissue explants and IL-1Ra production in these discs was assessed. This demonstrated that both nucleus pulposus and annulus fibrosus cells infected with Ad-IL-1Ra produced elevated levels of IL-1Ra for prolonged time periods, and these infected cells were resistant to IL-1. When the infected cells were injected into disc explants, IL-1Ra protein expression was increased which was maintained for 2 weeks of investigation. This in vitro study has shown that the use of ex vivo gene transfer to degenerate disc tissue is a feasible therapy for the inhibition of IL-1-mediated events during disc degeneration. PMID:16436110

Osmosis and viscoelasticity both contribute to time-dependent behaviour of the intervertebral disc under compressive load: A caprine in vitro study.

PubMed

Emanuel, Kaj S; van der Veen, Albert J; Rustenburg, Christine M E; Smit, Theodoor H; Kingma, Idsart

2018-03-21

The mechanical behaviour of the intervertebral disc highly depends on the content and transport of interstitial fluid. It is unknown, however, to what extent the time-dependent behaviour can be attributed to osmosis. Here we investigate the effect of both mechanical and osmotic loading on water content, nucleus pressure and disc height. Eight goat intervertebral discs, immersed in physiological saline, were subjected to a compressive force with a pressure needle inserted in the nucleus. The loading protocol was: 10 N (6 h); 150 N (42 h); 10 N (24 h). Half-way the 150 N-phase (24 h), we eliminated the osmotic gradient by adding 26% poly-ethylene glycol to the surrounding fluid. For 62 additional discs, we determined the water content of both nucleus and annulus after 6, 24, 48, or 72 h. The compressive load was initially counterbalanced by the hydrostatic pressure in the nucleus. The load forced 4.3% of the water out of the nucleus, which reduced nucleus pressure by 44(±6)%. Reduction of the osmotic gradient disturbed the equilibrium disc height, and a significant loss of annulus water content was found. Remarkably, pressure and water content of the nucleus pulposus remained unchanged. This shows that annulus water content is important in the response to axial loading. After unloading, in the absence of an osmotic gradient, there was substantial viscoelastic recovery of 53(±11)% of the disc height, without a change in water content. However, for restoration of the nucleus pressure and for full restoration of disc height, restoration of the osmotic gradient was needed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Senescent intervertebral disc cells exhibit perturbed matrix homeostasis phenotype.

PubMed

Ngo, Kevin; Patil, Prashanti; McGowan, Sara J; Niedernhofer, Laura J; Robbins, Paul D; Kang, James; Sowa, Gwendolyn; Vo, Nam

2017-09-01

Aging greatly increases the risk for intervertebral disc degeneration (IDD) as a result of proteoglycan loss due to reduced synthesis and enhanced degradation of the disc matrix proteoglycan (PG). How disc matrix PG homeostasis becomes perturbed with age is not known. The goal of this study is to determine whether cellular senescence is a source of this perturbation. We demonstrated that disc cellular senescence is dramatically increased in the DNA repair-deficient Ercc1 -/Δ mouse model of human progeria. In these accelerated aging mice, increased disc cellular senescence is closely associated with the rapid loss of disc PG. We also directly examine PG homeostasis in oxidative damage-induced senescent human cells using an in vitro cell culture model system. Senescence of human disc cells treated with hydrogen peroxide was confirmed by growth arrest, senescence-associated β-galactosidase activity, γH2AX foci, and acquisition of senescence-associated secretory phenotype. Senescent human disc cells also exhibited perturbed matrix PG homeostasis as evidenced by their decreased capacity to synthesize new matrix PG and enhanced degradation of aggrecan, a major matrix PG. of the disc. Our in vivo and in vitro findings altogether suggest that disc cellular senescence is an important driver of PG matrix homeostatic perturbation and PG loss. Published by Elsevier B.V.

Association between CT-evaluated lumbar lordosis and features of spinal degeneration, evaluated in supine position

PubMed Central

Kalichman, Leonid; Li, Ling; Hunter, David; Been, Ella

2013-01-01

Background Context Few studies have directly evaluated the association of lumbar lordosis and segmental wedging of the vertebral bodies and intervertebral disks with prevalence of spinal degenerative features. Purpose To evaluate the association of CT-evaluated lumbar lordosis, segmental wedging of the vertebral bodies and that of the intervertebral disks with various spinal degeneration features. Study design This cross-sectional study was a nested project to the Framingham Heart Study. Sample A random consecutive subset of 191 participants chosen from the 3590 participants enrolled in the Framingham Heart Study who underwent multi-detector CT to assess aortic calcification. Outcome Measures Physiologic Measures Dichotomous variables indicating the presence of intervertebral disc narrowing, facet joint osteoarthritis, spondylolysis, spondylolisthesis and spinal stenosis and density (in Hounsfield units) of multifidus and erector spinae muscles were evaluated on supine CT, as well as the lordosis angle (LA) and the wedging of the vertebral bodies and intervertebral disks. Sum of vertebral bodies wedging (ΣB) and sum of intervertebral discs wedging (ΣD) were used in analyses. Methods Mean values (±SD) of LA, ΣB and ΣD were calculated in males and females and compared using the t-test. Mean values (±SD) of LA, ΣB and ΣD in 4 age groups: <40, 40–49, 50–59 and 60+ years were calculated. We tested the linear relationship between LA, ΣB and ΣD and age groups. We evaluated the association between each spinal degeneration feature and LA, ΣB and ΣD using multiple logistic regression analysis where studied degeneration features were the dependent variable and all LA, ΣB and ΣD (separately) as well as age, sex, and BMI were independent predictors. Results LA was slightly lower than the normal range for standing individuals, and no difference was found between males and females (p=0.4107). However, the sex differences in sum of vertebral bodies wedging (ΣB) and sum of intervertebral discs wedging (ΣD) were statistically significant (0.0001 and 0.001, respectively). Females exhibit more dorsal wedging of the vertebral bodies and less dorsal wedging of the intervertebral discs than do males. All these parameters showed no association (p>0.05) with increasing age. LA showed statistically significant association with presence of spondylolysis (OR(95%CI): 1.08(1.02–1.14)) and with density of multifidus (1.06 (1.01–1.11). as well as a marginally significant association with isthmic spondylolisthesis (1.07(1.00–1.14). ΣB showed a positive association with degenerative spondylolisthesis and disc narrowing ((1.14(1.06–1.23) and 1.04 (1.00–1.08), correspondingly), whereas ΣD showed negative one (0.93(0.87–0.98) and (0.93(0.89–0.97), correspondingly). Conclusions Significant associations were found between lumbar lordosis evaluated in supine position and segmental wedging of the vertebral bodies and intervertebral disks and prevalence of spondylolysis and spondylolisthesis. Additional studies are needed, to evaluate the association between spondylolysis, isthmic and degenerative spondylolisthesis and vertebral and disc wedging at segmental level. PMID:21474082

In vivo performance of an acellular disc-like angle ply structure (DAPS) for total disc replacement in a small animal model.

PubMed

Martin, John T; Kim, Dong Hwa; Milby, Andrew H; Pfeifer, Christian G; Smith, Lachlan J; Elliott, Dawn M; Smith, Harvey E; Mauck, Robert L

2017-01-01

Total intervertebral disc replacement with a biologic engineered disc may be an alternative to spinal fusion for treating end-stage disc disease. In previous work, we developed disc-like angle ply structures (DAPS) that replicate the structure and function of the native disc and a rat tail model to evaluate DAPS in vivo. Here, we evaluated a strategy in which, after in vivo implantation, endogenous cells could colonize the acellular DAPS and form an extracellular matrix organized by the DAPS topographical template. To do so, acellular DAPS were implanted into the caudal spines of rats and evaluated over 12 weeks by mechanical testing, histology, and microcomputed tomography. An external fixation device was used to stabilize the implant site and various control groups were included to evaluate the effect of immobilization. There was robust tissue formation within the DAPS after implantation and compressive mechanical properties of the implant matched that of the native motion segment. Immobilization provided a stable site for fibrous tissue formation after either a discectomy or a DAPS implantation, but bony fusion eventually resulted, with segments showing intervertebral bridging after long-term implantation, a process that was accelerated by the implanted DAPS. Thus, while compressive mechanical properties were replicated after DAPS implantation, methods to actively prevent fusion must be developed. Future work will focus on limiting fusion by remobilizing the motion segment after a period of integration, delivering pro-chondrogenic factors, and pre-seeding DAPS with cells prior to implantation. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:23-31, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Measurement of intervertebral motion using quantitative fluoroscopy: report of an international forum and proposal for use in the assessment of degenerative disc disease in the lumbar spine.

PubMed

Breen, Alan C; Teyhen, Deydre S; Mellor, Fiona E; Breen, Alexander C; Wong, Kris W N; Deitz, Adam

2012-01-01

Quantitative fluoroscopy (QF) is an emerging technology for measuring intervertebral motion patterns to investigate problem back pain and degenerative disc disease. This International Forum was a networking event of three research groups (UK, US, Hong Kong), over three days in San Francisco in August 2009. Its aim was to reach a consensus on how best to record, analyse, and communicate QF information for research and clinical purposes. The Forum recommended that images should be acquired during regular trunk motion that is controlled for velocity and range, in order to minimise externally imposed variability as well as to correlate intervertebral motion with trunk motion. This should be done in both the recumbent passive and weight bearing active patient configurations. The main recommended outputs from QF were the true ranges of intervertebral rotation and translation, neutral zone laxity and the consistency of shape of the motion patterns. The main clinical research priority should initially be to investigate the possibility of mechanical subgroups of patients with chronic, nonspecific low back pain by comparing their intervertebral motion patterns with those of matched healthy controls.

Morphological changes of the caudal cervical intervertebral foramina due to flexion-extension and compression-traction movements in the canine cervical vertebral column.

PubMed

Ramos, Renato M; da Costa, Ronaldo C; Oliveira, Andre L A; Kodigudla, Manoj K; Goel, Vijay K

2015-08-06

Previous studies in humans have reported that the dimensions of the intervertebral foramina change significantly with movement of the spine. Cervical spondylomyelopathy (CSM) in dogs is characterized by dynamic and static compressions of the neural components, leading to variable degrees of neurologic deficits and neck pain. Studies suggest that intervertebral foraminal stenosis has implications in the pathogenesis of CSM. The dimensions of the cervical intervertebral foramina may significantly change during neck movements. This could have implication in the pathogenesis of CSM and other diseases associated with radiculopathy such as intervertebral disc disease. The purpose of this study was to quantify the morphological changes in the intervertebral foramina of dogs during flexion, extension, traction, and compression of the canine cervical vertebral column. All vertebral columns were examined with magnetic resonance imaging prior to biomechanic testing. Eight normal vertebral columns were placed in Group 1 and eight vertebral columns with intervertebral disc degeneration or/and protrusion were assigned to Group 2. Molds of the left and right intervertebral foramina from C4-5, C5-6 and C6-7 were taken during all positions and loading modes. Molds were frozen and vertical (height) and horizontal (width) dimensions of the foramina were measured. Comparisons were made between neutral to flexion and extension, flexion to extension, and traction to compression in neutral position. Extension decreased all the foraminal dimensions significantly, whereas flexion increased all the foraminal dimensions significantly. Compression decreased all the foraminal dimensions significantly, and traction increased the foraminal height, but did not significantly change the foraminal width. No differences in measurements were seen between groups. Our results show movement-related changes in the dimensions of the intervertebral foramina, with significant foraminal narrowing in extension and compression.

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

PubMed

Capoor, Manu N; Ruzicka, Filip; Schmitz, Jonathan E; James, Garth A; Machackova, Tana; Jancalek, Radim; Smrcka, Martin; Lipina, Radim; Ahmed, Fahad S; Alamin, Todd F; Anand, Neel; Baird, John C; Bhatia, Nitin; Demir-Deviren, Sibel; Eastlack, Robert K; Fisher, Steve; Garfin, Steven R; Gogia, Jaspaul S; Gokaslan, Ziya L; Kuo, Calvin C; Lee, Yu-Po; Mavrommatis, Konstantinos; Michu, Elleni; Noskova, Hana; Raz, Assaf; Sana, Jiri; Shamie, A Nick; Stewart, Philip S; Stonemetz, Jerry L; Wang, Jeffrey C; Witham, Timothy F; Coscia, Michael F; Birkenmaier, Christof; Fischetti, Vincent A; Slaby, Ondrej

2017-01-01

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

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

PubMed Central

Ruzicka, Filip; Schmitz, Jonathan E.; James, Garth A.; Machackova, Tana; Jancalek, Radim; Smrcka, Martin; Lipina, Radim; Ahmed, Fahad S.; Alamin, Todd F.; Anand, Neel; Baird, John C.; Bhatia, Nitin; Demir-Deviren, Sibel; Eastlack, Robert K.; Fisher, Steve; Garfin, Steven R.; Gogia, Jaspaul S.; Gokaslan, Ziya L.; Kuo, Calvin C.; Lee, Yu-Po; Mavrommatis, Konstantinos; Michu, Elleni; Noskova, Hana; Raz, Assaf; Sana, Jiri; Shamie, A. Nick; Stewart, Philip S.; Stonemetz, Jerry L.; Wang, Jeffrey C.; Witham, Timothy F.; Coscia, Michael F.; Birkenmaier, Christof; Fischetti, Vincent A.; Slaby, Ondrej

2017-01-01

Background In previous studies, Propionibacterium acnes was cultured from intervertebral disc tissue of ~25% of patients undergoing microdiscectomy, suggesting a possible link between chronic bacterial infection and disc degeneration. However, given the prominence of P. acnes as a skin commensal, such analyses often struggled to exclude the alternate possibility that these organisms represent perioperative microbiologic contamination. This investigation seeks to validate P. acnes prevalence in resected disc cultures, while providing microscopic evidence of P. acnes biofilm in the intervertebral discs. Methods Specimens from 368 patients undergoing microdiscectomy for disc herniation were divided into several fragments, one being homogenized, subjected to quantitative anaerobic culture, and assessed for bacterial growth, and a second fragment frozen for additional analyses. Colonies were identified by MALDI-TOF mass spectrometry and P. acnes phylotyping was conducted by multiplex PCR. For a sub-set of specimens, bacteria localization within the disc was assessed by microscopy using confocal laser scanning and FISH. Results Bacteria were cultured from 162 discs (44%), including 119 cases (32.3%) with P. acnes. In 89 cases, P. acnes was cultured exclusively; in 30 cases, it was isolated in combination with other bacteria (primarily coagulase-negative Staphylococcus spp.) Among positive specimens, the median P. acnes bacterial burden was 350 CFU/g (12 - ~20,000 CFU/g). Thirty-eight P. acnes isolates were subjected to molecular sub-typing, identifying 4 of 6 defined phylogroups: IA1, IB, IC, and II. Eight culture-positive specimens were evaluated by fluorescence microscopy and revealed P. acnes in situ. Notably, these bacteria demonstrated a biofilm distribution within the disc matrix. P. acnes bacteria were more prevalent in males than females (39% vs. 23%, p = 0.0013). Conclusions This study confirms that P. acnes is prevalent in herniated disc tissue. Moreover, it provides the first visual evidence of P. acnes biofilms within such specimens, consistent with infection rather than microbiologic contamination. PMID:28369127

Retroperitoneal oblique corridor to the L2-S1 intervertebral discs: an MRI study.

PubMed

Molinares, Diana M; Davis, Timothy T; Fung, Daniel A

2015-10-09

OBJECT The purpose of this study was to analyze MR images of the lumbar spine and document: 1) the oblique corridor at each lumbar disc level between the psoas muscle and the great vessels, and 2) oblique access to the L5-S1 disc space. Access to the lumbar spine without disruption of the psoas muscle could translate into decreased frequency of postoperative neurological complications observed after a transpsoas approach. The authors investigated the retroperitoneal oblique corridor of L2-S1 as a means of surgical access to the intervertebral discs. This oblique approach avoids the psoas muscle and is a safe and potentially superior alternative to the lateral transpsoas approach used by many surgeons. METHODS One hundred thirty-three MRI studies performed between May 4, 2012, and February 27, 2013, were randomly selected from the authors' database. Thirty-three MR images were excluded due to technical issues or altered lumbar anatomy due to previous spine surgery. The oblique corridor was defined as the distance between the left lateral border of the aorta (or iliac artery) and the anterior medial border of the psoas. The L5-S1 oblique corridor was defined transversely from the midsagittal line of the inferior endplate of L-5 to the medial border of the left common iliac vessel (axial view) and vertically to the first vascular structure that crossed midline (sagittal view). RESULTS The oblique corridor measurements to the L2-5 discs have the following mean distances: L2-3 = 16.04 mm, L3-4 = 14.21 mm, and L4-5 = 10.28 mm. The L5-S1 corridor mean distance was 10 mm between midline and left common iliac vessel, and 10.13 mm from the first midline vessel to the inferior endplate of L-5. The bifurcation of the aorta and confluence of the vena cava were also analyzed in this study. The aortic bifurcation was found at the L-3 vertebral body in 2% of the MR images, at the L3-4 disc in 5%, at the L-4 vertebral body in 43%, at the L4-5 disc in 11%, and at the L-5 vertebral body in 9%. The confluence of the iliac veins was found at lower levels: 45% at the L-4 level, 19.39% at the L4-5 intervertebral disc, and 34% at the L-5 vertebral body. CONCLUSIONS An oblique corridor of access to the L2-5 discs was found in 90% of the MR images (99% access to L2-3, 100% access to L3-4, and 91% access to L4-5). Access to the L5-S1 disc was also established in 69% of the MR images analyzed. The lower the confluence of iliac veins, the less probable it was that access to the L5-S1 intervertebral disc space was observed. These findings support the use of lumbar MRI as a tool to predetermine the presence of an oblique corridor for access to the L2-S1 intervertebral disc spaces prior to lumbar spine surgery.

The Effects of Glucosamine Sulfate on Intervertebral Disc Annulus Fibrosus Cells in Vitro

PubMed Central

Sowa, Gwendolyn; Coelho, J. Paulo; Jacobs, Lloydine; Komperda, Kasey; Sherry, Nora; Vo, Nam; Preuss, Harry; Balk, Judith; Kang, Jame

2014-01-01

Background context Glucosamine has gained widespread use among patients, despite inconclusive efficacy data. Inconsistency in the clinical literature may be related to lack of understanding of the effects of glucosamine on the intervertebral disc, and therefore, improper patient selection. Purpose The goal of our study was to investigate the effects of glucosamine on intervertebral disc cells in vitro under the physiological conditions of inflammation and mechanical loading. Study Design Controlled in vitro laboratory setting Methods Intervertebral disc cells isolated from the rabbit annulus fibrosus were exposed to glucosamine sulfate in the presence and absence of interleukin-1beta and tensile strain. Outcome measures included gene expression, measurement of total glycosaminoglycans, new proteoglycan synthesis, prostaglandin E2 production, and matrix metalloproteinase activity. The study was funded by NIH/NCCAM and the authors have no conflicts of interest. Results Under conditions of inflammatory stimulation alone, glucosamine demonstrated a dose dependent effect in decreasing inflammatory and catabolic mediators and increasing anabolic genes. However, under conditions of mechanical stimulation, although inflammatory gene expression was decreased, PGE2 was not. In addition, MMP-3 gene expression was increased and aggrecan expression decreased, both of which would have a detrimental effect on matrix homeostasis. Consistent with this, measurement of total glycosaminoglycans and new proteoglycan synthesis demonstrated detrimental effects of glucosamine under all conditions tested. Conclusions These results may in part help to explain the conflicting reports of efficacy, as there is biological plausibility for a therapeutic effect under conditions of predominate inflammation, but not under conditions where mechanical loading is present or in which matrix synthesis is needed. PMID:24361347

Upregulation of nuclear factor‑κB and acid sensing ion channel 3 in dorsal root ganglion following application of nucleus pulposus onto the nerve root in rats.

PubMed

Wang, Dong; Pan, Hao; Zhu, Hang; Zhu, Li; He, Yong-Jiang; Wang, Jian; Jia, Gao-Yong

2017-10-01

The nucleus pulposus (NP) is an avascular, hydrated tissue that permits the intervertebral disc to resist compressive loads to the spine. To determine the mechanisms by which intervertebral disc degeneration is caused by the nucleus pulposus, the expression and regulation of nuclear factor (NF)‑κB and acid sensing ion channel 3 (ASIC3) were examined. For the intervertebral disc degeneration model, NP was harvested from the tail of rats and applied to the L5 dorsal root ganglion (DRG). The mechanical pain withdrawal threshold (PWT) in NP model rats was assessed. Reverse transcription‑quantitative polymerase chain reaction and western blotting were used to examine NF‑κB and ASIC3 expression levels in DRG. Finally, the effect of the NF‑κB inhibitor pyrrolidine dithiocarbamate (PDTC) and the ASIC3 signaling pathway blocker amiloride were examined. Rats exposed to NP exhibited decreased PWT for 12 days, and NF‑κB and ASIC3 was upregulated in DRG induced by NP 14 days after surgery. After administration of amiloride and PDTC to DRG affected by NP, the levels of nitric oxide (NO), tumor necrosis factor‑α (TNF‑α), interleukin‑6 (IL‑6), NF‑κB and ASIC3 were downregulated, and the levels of aquaporin (AQP) 1 and AQP3 were significantly increased for 14 days. In conclusion, these results suggested that NF‑κB and ASIC3 may serve an important role in intervertebral disc degeneration caused by NP.

Decreased physical function and increased pain sensitivity in mice deficient for type IX collagen.

PubMed

Allen, Kyle D; Griffin, Timothy M; Rodriguiz, Ramona M; Wetsel, William C; Kraus, Virginia B; Huebner, Janet L; Boyd, Lawrence M; Setton, Lori A

2009-09-01

In mice with Col9a1 gene inactivation (Col9a1(-/-)), osteoarthritis (OA) and intervertebral disc degeneration develop prematurely. The aim of this study was to investigate Col9a1(-/-) mice for functional and symptomatic changes that may be associated with these pathologies. Col9a1(-/-) and wild-type mice were investigated for reflexes, functional impairment (beam walking, pole climbing, wire hang, grip strength), sensorimotor skills (rotarod), mechanical sensitivity (von Frey hair), and thermal sensitivity (hot plate/tail flick). Gait was also analyzed to determine velocity, stride frequency, symmetry, percentage stance time, stride length, and step width. Postmortem, sera obtained from the mice were analyzed for hyaluronan, and their knees and spines were graded histologically for degeneration. Col9a1(-/-) mice had compensatory gait changes, increased mechanical sensitivity, and impaired physical ability. Col9a1(-/-) mice ambulated with gaits characterized by increased percentage stance times and shorter stride lengths. These mice also had heightened mechanical sensitivity and were deficient in contact righting, wire hang, rotarod, and pole climbing tasks. Male Col9a1(-/-) mice had the highest mean serum hyaluronan levels and strong histologic evidence of cartilage erosion. Intervertebral disc degeneration was also detected, with Col9a1(-/-) mice having an increased incidence of disc tears. These data describe a Col9a1(-/-) behavioral phenotype characterized by altered gait, increased mechanical sensitivity, and impaired function. These gait and functional differences suggest that Col9a1(-/-) mice select locomotive behaviors that limit joint loads. The nature and magnitude of behavioral changes were largest in male mice, which also had the greatest evidence of knee degeneration. These findings suggest that Col9a1(-/-) mice present behavioral changes consistent with anatomic signs of OA and intervertebral disc degeneration.

Examination of a lumbar spine biomechanical model for assessing axial compression, shear, and bending moment using selected Olympic lifts.

PubMed

Eltoukhy, Moataz; Travascio, Francesco; Asfour, Shihab; Elmasry, Shady; Heredia-Vargas, Hector; Signorile, Joseph

2016-09-01

Loading during concurrent bending and compression associated with deadlift, hang clean and hang snatch lifts carries the potential for injury to the intervertebral discs, muscles and ligaments. This study examined the capacity of a newly developed spinal model to compute shear and compressive forces, and bending moments in lumbar spine for each lift. Five male subjects participated in the study. The spine was modeled as a chain of rigid bodies (vertebrae) connected via the intervertebral discs. Each vertebral reference frame was centered in the center of mass of the vertebral body, and its principal directions were axial, anterior-posterior, and medial-lateral. The results demonstrated the capacity of this spinal model to assess forces and bending moments at and about the lumbar vertebrae by showing the variations among these variables with different lifting techniques. These results show the model's potential as a diagnostic tool.

A rare case of spontaneous Aspergillus spondylodiscitis with epidural abscess in a 45-year-old immunocompetent female

PubMed Central

Raj, K. Ambedkar; Srinivasamurthy, Banushree C.; Nagarajan, Krishnan; Sinduja, M. G. Ilavarasi

2013-01-01

Vertebral osteomyelitis and discitis are mainly due to bacterial infections though fungal infections are one of the important causes of morbidity and mortality in immunocompromised patients. Aspergillus involving intervertebral disc space is extremely rare. We report a case of aspergillosis of intervertebral L5-S1 disc space with spinal epidural abscess in an immunocompetent 45-year-old female which can add on to a few case reports described in literature as well as an insight for clinicians regarding this rare spontaneous infection in an immunocompetent patient. PMID:24744568

A rare case of spontaneous Aspergillus spondylodiscitis with epidural abscess in a 45-year-old immunocompetent female.

PubMed

Raj, K Ambedkar; Srinivasamurthy, Banushree C; Nagarajan, Krishnan; Sinduja, M G Ilavarasi

2013-07-01

Vertebral osteomyelitis and discitis are mainly due to bacterial infections though fungal infections are one of the important causes of morbidity and mortality in immunocompromised patients. Aspergillus involving intervertebral disc space is extremely rare. We report a case of aspergillosis of intervertebral L5-S1 disc space with spinal epidural abscess in an immunocompetent 45-year-old female which can add on to a few case reports described in literature as well as an insight for clinicians regarding this rare spontaneous infection in an immunocompetent patient.

Multidirectional testing of one- and two-level ProDisc-L versus simulated fusions.

PubMed

Panjabi, Manohar; Henderson, Gweneth; Abjornson, Celeste; Yue, James

2007-05-20

An in vitro human cadaveric biomechanical study. To evaluate intervertebral rotation changes due to lumbar ProDisc-L compared with simulated fusion, using follower load and multidirectional testing. Artificial discs, as opposed to the fusions, are thought to decrease the long-term accelerated degeneration at adjacent levels. A biomechanical assessment can be helpful, as the long-term clinical evaluation is impractical. Six fresh human cadaveric lumbar specimens (T12-S1) underwent multidirectional testing in flexion-extension, bilateral lateral bending, and bilateral torsion using the Hybrid test method. First, intact specimen total range of rotation (T12-S1) was determined. Second, using pure moments again, this range of rotation was achieved in each of the 5 constructs: A) ProDisc-L at L5-S1; B) fusion at L5-S1; C) ProDisc-L at L4-L5 and fusion at L5-S1; D) ProDisc-L at L4-L5 and L5-S1; and E) 2-level fusion at L4-L5 to L5-S1. Significant changes in the intervertebral rotations due to each construct were determined at the operated and nonoperated levels using repeated measures single factor ANOVA and Bonferroni statistical tests (P < 0.05). Adjacent-level effects (ALEs) were defined as the percentage changes in intervertebral rotations at the nonoperated levels due to the constructs. One- and 2-level ProDisc-L constructs showed only small ALE in any of the 3 rotations. In contrast, 1- and 2-level fusions showed increased ALE in all 3 directions (average, 7.8% and 35.3%, respectively, for 1 and 2 levels). In the disc plus fusion combination (construct C), the ALEs were similar to the 1-level fusion alone. In general, ProDisc-L preserved physiologic motions at all spinal levels, while the fusion simulations resulted in significant ALE.

ISSLS PRIZE IN BIOENGINEERING SCIENCE 2017: Automation of reading of radiological features from magnetic resonance images (MRIs) of the lumbar spine without human intervention is comparable with an expert radiologist.

PubMed

Jamaludin, Amir; Lootus, Meelis; Kadir, Timor; Zisserman, Andrew; Urban, Jill; Battié, Michele C; Fairbank, Jeremy; McCall, Iain

2017-05-01

Investigation of the automation of radiological features from magnetic resonance images (MRIs) of the lumbar spine. To automate the process of grading lumbar intervertebral discs and vertebral bodies from MRIs. MR imaging is the most common imaging technique used in investigating low back pain (LBP). Various features of degradation, based on MRIs, are commonly recorded and graded, e.g., Modic change and Pfirrmann grading of intervertebral discs. Consistent scoring and grading is important for developing robust clinical systems and research. Automation facilitates this consistency and reduces the time of radiological analysis considerably and hence the expense. 12,018 intervertebral discs, from 2009 patients, were graded by a radiologist and were then used to train: (1) a system to detect and label vertebrae and discs in a given scan, and (2) a convolutional neural network (CNN) model that predicts several radiological gradings. The performance of the model, in terms of class average accuracy, was compared with the intra-observer class average accuracy of the radiologist. The detection system achieved 95.6% accuracy in terms of disc detection and labeling. The model is able to produce predictions of multiple pathological gradings that consistently matched those of the radiologist. The model identifies 'Evidence Hotspots' that are the voxels that most contribute to the degradation scores. Automation of radiological grading is now on par with human performance. The system can be beneficial in aiding clinical diagnoses in terms of objectivity of gradings and the speed of analysis. It can also draw the attention of a radiologist to regions of degradation. This objectivity and speed is an important stepping stone in the investigation of the relationship between MRIs and clinical diagnoses of back pain in large cohorts. Level 3.

Comparison of animal discs used in disc research to human lumbar disc: torsion mechanics and collagen content.

PubMed

Showalter, Brent L; Beckstein, Jesse C; Martin, John T; Beattie, Elizabeth E; Espinoza Orías, Alejandro A; Schaer, Thomas P; Vresilovic, Edward J; Elliott, Dawn M

2012-07-01

Experimental measurement and normalization of in vitro disc torsion mechanics and collagen content for several animal species used in intervertebral disc research and comparing these with the human disc. To aid in the selection of appropriate animal models for disc research by measuring torsional mechanical properties and collagen content. There is lack of data and variability in testing protocols for comparing animal and human disc torsion mechanics and collagen content. Intervertebral disc torsion mechanics were measured and normalized by disc height and polar moment of inertia for 11 disc types in 8 mammalian species: the calf, pig, baboon, goat, sheep, rabbit, rat, and mouse lumbar discs, and cow, rat, and mouse caudal discs. Collagen content was measured and normalized by dry weight for the same discs except the rat and the mouse. Collagen fiber stretch in torsion was calculated using an analytical model. Measured torsion parameters varied by several orders of magnitude across the different species. After geometric normalization, only the sheep and pig discs were statistically different from human discs. Fiber stretch was found to be highly dependent on the assumed initial fiber angle. The collagen content of the discs was similar, especially in the outer annulus where only the calf and goat discs were statistically different from human. Disc collagen content did not correlate with torsion mechanics. Disc torsion mechanics are comparable with human lumbar discs in 9 of 11 disc types after normalization by geometry. The normalized torsion mechanics and collagen content of the multiple animal discs presented are useful for selecting and interpreting results for animal disc models. Structural organization of the fiber angle may explain the differences that were noted between species after geometric normalization.

Dysregulation of YAP by the Hippo pathway is involved in intervertebral disc degeneration, cell contact inhibition, and cell senescence.

PubMed

Zhang, Cong; Wang, Feng; Xie, Zhiyang; Chen, Lu; Sinkemani, Arjun; Yu, Haomin; Wang, Kun; Mao, Lu; Wu, Xiaotao

2018-01-05

The Hippo pathway plays important roles in wound healing, tissue repair and regeneration, and in the treatment of degenerative diseases, by regulating cell proliferation and apoptosis in mammals. Intervertebral disc degeneration (IDD) is one of the major causes of low back pain, a widespread issue associated with a heavy economic burden. However, the mechanism underlying how the Hippo pathway regulates IDD is not well understood. Here, we demonstrate that the Hippo pathway is involved in natural IDD. Activation and dephosphorylation of yes-associated protein (YAP) were observed in younger rat discs, and decreased gradually with age. Surprisingly, Hippo pathway suppression was accompanied by overexpression of YAP, caused by acute disc injury, suggesting a limited ability for self-repair in IDD. We also demonstrated that YAP is inhibited by cell-to-cell contact via the Hippo pathway in vitro . Phosphorylation by large tumor suppressor kinases 1/2 (LATS1/2) led to cytoplasmic translocation and inactivation of YAP. YAP dephosphorylation was mainly localized in the nucleus and regulated by the Hippo pathway, whereas YAP dephosphorylation occurred in the cytoplasm and was associated with nucleus pulposus cell (NPC) senescence. Moreover, NPCs were transfected with shYAP and it accelerates the premature senescence of cells by interfered Hippo pathway through YAP. Therefore, our results indicate that the Hippo pathway plays an important role in maintaining the homeostasis of intervertebral discs and controlling NPC proliferation.

[Biology and mechanobiology of the intervertebral disc].

PubMed

González Martínez, Emilio; García-Cosamalón, José; Cosamalón-Gan, Iván; Esteban Blanco, Marta; García-Suarez, Olivia; Vega, José A

The intervertebral disc (IVD) is noted for its low cell content, and being the largest avascular structure of human body. The low amount of cells in the disc have to adapt to an anaerobic metabolism with low oxygen pressure and acidic pH. Apart from surviving in an adverse microenvironment, they are exposed to a high level of mechanical stress. The biological adaptation of cells to acidosis and hyperosmolarity conditions are regulated by mechanoproteins, which are responsible for converting a mechanical signal into a cellular response, thus modifying its gene expression. Mechanobiology helps us to better understand the pathophysiology of IVD and its potential biological repair. Copyright © 2016 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

Percutaneous treatment of intervertebral disc herniation.

PubMed

Buy, Xavier; Gangi, Afshin

2010-06-01

Interventional radiology plays a major role in the management of symptomatic intervertebral disc herniations. In the absence of significant pain relief with conservative treatment including oral pain killers and anti-inflammatory drugs, selective image-guided periradicular infiltrations are generally indicated. The precise control of needle positioning allows optimal distribution of steroids along the painful nerve root. After 6 weeks of failure of conservative treatment including periradicular infiltration, treatment aiming to decompress or remove the herniation is considered. Conventional open surgery offers suboptimal results and is associated with significant morbidity. To achieve minimally invasive discal decompression, different percutaneous techniques have been developed. Their principle is to remove a small volume of nucleus, which results in an important reduction of intradiscal pressure and subsequently reduction of pressure inside the disc herniation. However, only contained disc herniations determined by computed tomography or magnetic resonance are indicated for these techniques. Thermal techniques such as radiofrequency or laser nucleotomy seem to be more effective than purely mechanical nucleotomy; indeed, they achieve discal decompression but also thermal destruction of intradiscal nociceptors, which may play a major role in the physiopathology of discal pain. The techniques of image-guided spinal periradicular infiltration and percutaneous nucleotomy with laser and radiofrequency are presented with emphasis on their best indications.

Comparison of Animal Discs Used in Disc Research to Human Lumbar Disc: Torsion Mechanics and Collagen Content

PubMed Central

Showalter, Brent L.; Beckstein, Jesse C.; Martin, John T.; Beattie, Elizabeth E.; Orías, Alejandro A. Espinoza; Schaer, Thomas P.; Vresilovic, Edward J.; Elliott, Dawn M.

2012-01-01

Study Design Experimental measurement and normalization of in vitro disc torsion mechanics and collagen content for several animal species used in intervertebral disc research and comparing these to the human disc. Objective To aid in the selection of appropriate animal models for disc research by measuring torsional mechanical properties and collagen content. Summary of Background Data There is lack of data and variability in testing protocols for comparing animal and human disc torsion mechanics and collagen content. Methods Intervertebral disc torsion mechanics were measured and normalized by disc height and polar moment of inertia for 11 disc types in 8 mammalian species: the calf, pig, baboon, goat, sheep, rabbit, rat, and mouse lumbar, and cow, rat, and mouse caudal. Collagen content was measured and normalized by dry weight for the same discs except the rat and mouse. Collagen fiber stretch in torsion was calculated using an analytical model. Results Measured torsion parameters varied by several orders of magnitude across the different species. After geometric normalization, only the sheep and pig discs were statistically different from human. Fiber stretch was found to be highly dependent on the assumed initial fiber angle. The collagen content of the discs was similar, especially in the outer annulus where only the calf and goat discs were statistically different from human. Disc collagen content did not correlate with torsion mechanics. Conclusion Disc torsion mechanics are comparable to human lumbar discs in 9 of 11 disc types after normalization by geometry. The normalized torsion mechanics and collagen content of the multiple animal discs presented is useful for selecting and interpreting results for animal models of the disc. Structural composition of the disc, such as initial fiber angle, may explain the differences that were noted between species after geometric normalization. PMID:22333953

Development of Ultrasound to Measure In-vivo Dynamic Cervical Spine Intervertebral Disc Mechanics

DTIC Science & Technology

2014-01-01

The deformation between C4 and C6 measured by the US probe was affected by bulging of the IVD and soft tissues during compressive loading as...endplates of the vertebrae and cartilaginous endplate of the discs were added to all segments. Figure 28 Coronal views of the updated C4-T1 FEM (a...the ligaments and soft tissue connections that provide stability to the cervical spine FSUs were added (Figures 30 and 31). For the anterior

Wnt signaling activates Shh signaling in early postnatal intervertebral discs, and re-activates Shh signaling in old discs in the mouse.

PubMed

Winkler, Tamara; Mahoney, Eric J; Sinner, Debora; Wylie, Christopher C; Dahia, Chitra Lekha

2014-01-01

Intervertebral discs (IVDs) are strong fibrocartilaginous joints that connect adjacent vertebrae of the spine. As discs age they become prone to failure, with neurological consequences that are often severe. Surgical repair of discs treats the result of the disease, which affects as many as one in seven people, rather than its cause. An ideal solution would be to repair degenerating discs using the mechanisms of their normal differentiation. However, these mechanisms are poorly understood. Using the mouse as a model, we previously showed that Shh signaling produced by nucleus pulposus cells activates the expression of differentiation markers, and cell proliferation, in the postnatal IVD. In the present study, we show that canonical Wnt signaling is required for the expression of Shh signaling targets in the IVD. We also show that Shh and canonical Wnt signaling pathways are down-regulated in adult IVDs. Furthermore, this down-regulation is reversible, since re-activation of the Wnt or Shh pathways in older discs can re-activate molecular markers of the IVD that are lost with age. These data suggest that biological treatments targeting Wnt and Shh signaling pathways may be feasible as a therapeutic for degenerative disc disease.

Finite element based nonlinear normalization of human lumbar intervertebral disc stiffness to account for its morphology.

PubMed

Maquer, Ghislain; Laurent, Marc; Brandejsky, Vaclav; Pretterklieber, Michael L; Zysset, Philippe K

2014-06-01

Disc degeneration, usually associated with low back pain and changes of intervertebral stiffness, represents a major health issue. As the intervertebral disc (IVD) morphology influences its stiffness, the link between mechanical properties and degenerative grade is partially lost without an efficient normalization of the stiffness with respect to the morphology. Moreover, although the behavior of soft tissues is highly nonlinear, only linear normalization protocols have been defined so far for the disc stiffness. Thus, the aim of this work is to propose a nonlinear normalization based on finite elements (FE) simulations and evaluate its impact on the stiffness of human anatomical specimens of lumbar IVD. First, a parameter study involving simulations of biomechanical tests (compression, flexion/extension, bilateral torsion and bending) on 20 FE models of IVDs with various dimensions was carried out to evaluate the effect of the disc's geometry on its compliance and establish stiffness/morphology relations necessary to the nonlinear normalization. The computed stiffness was then normalized by height (H), cross-sectional area (CSA), polar moment of inertia (J) or moments of inertia (Ixx, Iyy) to quantify the effect of both linear and nonlinear normalizations. In the second part of the study, T1-weighted MRI images were acquired to determine H, CSA, J, Ixx and Iyy of 14 human lumbar IVDs. Based on the measured morphology and pre-established relation with stiffness, linear and nonlinear normalization routines were then applied to the compliance of the specimens for each quasi-static biomechanical test. The variability of the stiffness prior to and after normalization was assessed via coefficient of variation (CV). The FE study confirmed that larger and thinner IVDs were stiffer while the normalization strongly attenuated the effect of the disc geometry on its stiffness. Yet, notwithstanding the results of the FE study, the experimental stiffness showed consistently higher CV after normalization. Assuming that geometry and material properties affect the mechanical response, they can also compensate for one another. Therefore, the larger CV after normalization can be interpreted as a strong variability of the material properties, previously hidden by the geometry's own influence. In conclusion, a new normalization protocol for the intervertebral disc stiffness in compression, flexion, extension, bilateral torsion and bending was proposed, with the possible use of MRI and FE to acquire the discs' anatomy and determine the nonlinear relations between stiffness and morphology. Such protocol may be useful to relate the disc's mechanical properties to its degree of degeneration.

Prevalence of Propionibacterium acnes in Intervertebral Discs of Patients Undergoing Lumbar Microdiscectomy: A Prospective Cross-Sectional Study

PubMed Central

Capoor, Manu N.; Ruzicka, Filip; Machackova, Tana; Jancalek, Radim; Smrcka, Martin; Schmitz, Jonathan E.; Hermanova, Marketa; Sana, Jiri; Michu, Elleni; Baird, John C.; Ahmed, Fahad S.; Maca, Karel; Lipina, Radim; Alamin, Todd F.; Coscia, Michael F.; Stonemetz, Jerry L.; Witham, Timothy; Ehrlich, Garth D.; Gokaslan, Ziya L.; Mavrommatis, Konstantinos; Birkenmaier, Christof; Fischetti, Vincent A.; Slaby, Ondrej

2016-01-01

Background The relationship between intervertebral disc degeneration and chronic infection by Propionibacterium acnes is controversial with contradictory evidence available in the literature. Previous studies investigating these relationships were under-powered and fraught with methodical differences; moreover, they have not taken into consideration P. acnes’ ability to form biofilms or attempted to quantitate the bioburden with regard to determining bacterial counts/genome equivalents as criteria to differentiate true infection from contamination. The aim of this prospective cross-sectional study was to determine the prevalence of P. acnes in patients undergoing lumbar disc microdiscectomy. Methods and Findings The sample consisted of 290 adult patients undergoing lumbar microdiscectomy for symptomatic lumbar disc herniation. An intraoperative biopsy and pre-operative clinical data were taken in all cases. One biopsy fragment was homogenized and used for quantitative anaerobic culture and a second was frozen and used for real-time PCR-based quantification of P. acnes genomes. P. acnes was identified in 115 cases (40%), coagulase-negative staphylococci in 31 cases (11%) and alpha-hemolytic streptococci in 8 cases (3%). P. acnes counts ranged from 100 to 9000 CFU/ml with a median of 400 CFU/ml. The prevalence of intervertebral discs with abundant P. acnes (≥ 1x103 CFU/ml) was 11% (39 cases). There was significant correlation between the bacterial counts obtained by culture and the number of P. acnes genomes detected by real-time PCR (r = 0.4363, p<0.0001). Conclusions In a large series of patients, the prevalence of discs with abundant P. acnes was 11%. We believe, disc tissue homogenization releases P. acnes from the biofilm so that they can then potentially be cultured, reducing the rate of false-negative cultures. Further, quantification study revealing significant bioburden based on both culture and real-time PCR minimize the likelihood that observed findings are due to contamination and supports the hypothesis P. acnes acts as a pathogen in these cases of degenerative disc disease. PMID:27536784

Prevalence of Propionibacterium acnes in Intervertebral Discs of Patients Undergoing Lumbar Microdiscectomy: A Prospective Cross-Sectional Study.

PubMed

Capoor, Manu N; Ruzicka, Filip; Machackova, Tana; Jancalek, Radim; Smrcka, Martin; Schmitz, Jonathan E; Hermanova, Marketa; Sana, Jiri; Michu, Elleni; Baird, John C; Ahmed, Fahad S; Maca, Karel; Lipina, Radim; Alamin, Todd F; Coscia, Michael F; Stonemetz, Jerry L; Witham, Timothy; Ehrlich, Garth D; Gokaslan, Ziya L; Mavrommatis, Konstantinos; Birkenmaier, Christof; Fischetti, Vincent A; Slaby, Ondrej

2016-01-01

The relationship between intervertebral disc degeneration and chronic infection by Propionibacterium acnes is controversial with contradictory evidence available in the literature. Previous studies investigating these relationships were under-powered and fraught with methodical differences; moreover, they have not taken into consideration P. acnes' ability to form biofilms or attempted to quantitate the bioburden with regard to determining bacterial counts/genome equivalents as criteria to differentiate true infection from contamination. The aim of this prospective cross-sectional study was to determine the prevalence of P. acnes in patients undergoing lumbar disc microdiscectomy. The sample consisted of 290 adult patients undergoing lumbar microdiscectomy for symptomatic lumbar disc herniation. An intraoperative biopsy and pre-operative clinical data were taken in all cases. One biopsy fragment was homogenized and used for quantitative anaerobic culture and a second was frozen and used for real-time PCR-based quantification of P. acnes genomes. P. acnes was identified in 115 cases (40%), coagulase-negative staphylococci in 31 cases (11%) and alpha-hemolytic streptococci in 8 cases (3%). P. acnes counts ranged from 100 to 9000 CFU/ml with a median of 400 CFU/ml. The prevalence of intervertebral discs with abundant P. acnes (≥ 1x103 CFU/ml) was 11% (39 cases). There was significant correlation between the bacterial counts obtained by culture and the number of P. acnes genomes detected by real-time PCR (r = 0.4363, p<0.0001). In a large series of patients, the prevalence of discs with abundant P. acnes was 11%. We believe, disc tissue homogenization releases P. acnes from the biofilm so that they can then potentially be cultured, reducing the rate of false-negative cultures. Further, quantification study revealing significant bioburden based on both culture and real-time PCR minimize the likelihood that observed findings are due to contamination and supports the hypothesis P. acnes acts as a pathogen in these cases of degenerative disc disease.

Graph cuts with invariant object-interaction priors: application to intervertebral disc segmentation.

PubMed

Ben Ayed, Ismail; Punithakumar, Kumaradevan; Garvin, Gregory; Romano, Walter; Li, Shuo

2011-01-01

This study investigates novel object-interaction priors for graph cut image segmentation with application to intervertebral disc delineation in magnetic resonance (MR) lumbar spine images. The algorithm optimizes an original cost function which constrains the solution with learned prior knowledge about the geometric interactions between different objects in the image. Based on a global measure of similarity between distributions, the proposed priors are intrinsically invariant with respect to translation and rotation. We further introduce a scale variable from which we derive an original fixed-point equation (FPE), thereby achieving scale-invariance with only few fast computations. The proposed priors relax the need of costly pose estimation (or registration) procedures and large training sets (we used a single subject for training), and can tolerate shape deformations, unlike template-based priors. Our formulation leads to an NP-hard problem which does not afford a form directly amenable to graph cut optimization. We proceeded to a relaxation of the problem via an auxiliary function, thereby obtaining a nearly real-time solution with few graph cuts. Quantitative evaluations over 60 intervertebral discs acquired from 10 subjects demonstrated that the proposed algorithm yields a high correlation with independent manual segmentations by an expert. We further demonstrate experimentally the invariance of the proposed geometric attributes. This supports the fact that a single subject is sufficient for training our algorithm, and confirms the relevance of the proposed priors to disc segmentation.

Failed back surgery syndrome: the role of symptomatic segmental single-level instability after lumbar microdiscectomy.

PubMed

Schaller, B

2004-05-01

Segmental instability represents one of several different factors that may cause or contribute to the failed back surgery syndrome after lumbar microdiscectomy. As segmental lumbar instability poses diagnostic problems by lack of clear radiological and clinical criteria, only little is known about the occurrence of this phenomenon following primary microdiscectomy. Retrospectively, the records of 2,353 patients were reviewed according to postoperative symptomatic segmental single-level instability after lumbar microdiscectomy between 1989 and 1997. Progressive neurological deficits increased (mean of 24 months; SD: 12, range 1-70) after the initial surgical procedure in 12 patients. The mean age of the four men and eight women was 43 years (SD: 6, range 40-77). The main symptoms and signs of secondary neurological deterioration were radicular pain in 9 of 12 patients, increased motor weakness in 6 of 12 patients and sensory deficits in 4 of 12 patients. All 12 symptomatic patients had radiological evidence of segmental changes correlating with the clinical symptoms and signs. All but one patient showed a decrease in the disc height greater than 30% at the time of posterior spondylodesis compared with the preoperative images before lumbar microdiscectomy. All patients underwent secondary laminectomy and posterior lumbar sponylodesis. Postoperatively, pain improved in 8 of 9 patients, motor weakness in 3 of 6 patients, and sensory deficits in 2 of 4 patients. During the follow-up period of 72+/-7 months, one patient required a third operation to alleviate spinal stenosis at the upper end of the laminectomy. Patients with secondary segmental instability following microdiscectomy were mainly in their 40s. Postoperative narrowing of the intervertebral space following lumbar microdiscectomy is correlated to the degree of intervertebral disc resection. It can therefore be concluded that (1) patients in their 40s are prone to postoperative narrowing of the intervertebral disc space and hence subsequent intervertebral instability and (2) that a small extent of intervertebral disc resection and preservation of the "segmental frame" may be beneficial in those patients. The present study demonstrated for the first time that the degree of extensive operative techniques in microdiscectomy increased the risk of subsequent segmental instability. In addition, narrowing of the intervertebral space of more than 30% represents a clear radiological sign of segmental instability.

The Role of Adipokines in Intervertebral Disc Degeneration.

PubMed

Sharma, Anirudh

2018-04-24

Intervertebral disc degeneration (IDD) is an important cause of low back pain. Recent evidence suggests that in addition to abnormal and excessive mechanical loading, inflammation may be a key driver for both IDD and low back pain. Obesity, a known mechanical risk factor of IDD, is now increasingly being recognized as a systemic inflammatory state with adipokines being postulated as likely inflammatory mediators. The aim of this review was to summarize the current literature regarding the inflammatory role of adipokines in the pathophysiology of IDD. A systematic literature search was performed using the OVID Medline, EMBASE and PubMed databases to identify all studies assessing IDD and adipokines. Fifteen studies were included in the present review. Leptin was the most commonly assessed adipokine. Ten of 15 studies were conducted in humans; three in rats and two in both humans and rats. Studies focused on a variety of topics ranging from receptor identification, pathway analysis, genetic associations, and proteonomics. Currently, data from both human and animal experiments demonstrate significant effects of leptin and adiponectin on the internal milieu of intervertebral discs. However, future studies are needed to determine the molecular pathway relationships between adipokines in the pathophysiology of IDD as avenues for future therapeutic targets.

Morphometric Study of the Lumbar Posterior Longitudinal Ligament

PubMed Central

Lee, Sang Beom; Chang, Jae Chil; Lee, Gwang Soo; Hwang, Jae Chan; Bae, Hack Gun; Doh, Jae Won

2018-01-01

Objective Morphometric data for the lumbar posterior longitudinal ligament (PLL) was investigated to identify whether there is a difference in the morphometry of the PLL of the lumbar spine at each level with respect to the pattern of intervertebral disc displacement. Methods In 14 formalin-fixed adult cadavers (12 males and 2 females), from L1 to L5, the authors measured the width and height of the PLL and compared them with other landmarks such as the disc and the pedicle. Results Horizontally, at the upper margin of the disc, the central portion of the superficial PLL covered 17.8–36.9% of the disc width and the fan-like portion of the PLL covered 63.9–76.7% of the disc width. At the level of the median portion of the disc, the PLL covered 69.1–74.5% of the disc width. Vertically, at the level of the medial margin of the pedicle, the fan-like portion of the PLL covered 23.5–29.9% of the disc height. In general, a significant difference in length was not found in the right-left and male-female comparisons. Conclusion This study presents the morphometric data on the pattern of intervertebral disc displacement and helps to improve the knowledge of the surgical anatomy of the lumbar PLL. PMID:29354240

Human Cartilage Endplate Permeability Varies with Degeneration and Intervertebral Disc Site

PubMed Central

DeLucca, John F.; Cortes, Daniel H.; Jacobs, Nathan T.; Vresilovic, Edward J.; Duncan, Randall L.; Elliott, Dawn M.

2016-01-01

Despite the critical functions the human cartilage endplate (CEP) plays in the intervertebral disc, little is known about its structural and mechanical properties and their changes with degeneration. Quantifying these changes with degeneration is important for understanding how the CEP contributes to the function and pathology of the disc. Therefore the objectives of this study were to quantify the effect of disc degeneration on human CEP mechanical properties, determine the influence of superior and inferior disc site on mechanics and composition, and simulate the role of collagen fibers in CEP and disc mechanics using a validated finite element model. Confined compression data and biochemical composition data were used in a biphasic-swelling model to calculate compressive extrafibrillar elastic and permeability properties. Tensile properties were obtained by applying published tensile test data to an ellipsoidal fiber distribution. Results showed that with degeneration CEP permeability decreased 50–60% suggesting that transport is inhibited in the degenerate disc. CEP fibers are organized parallel to the vertebrae and nucleus pulposus and may contribute to large shear strains (0.1–0.2) and delamination failure of the CEP commonly seen in herniated disc tissue. Fiber-reinforcement also reduces CEP axial strains thereby enhancing fluid flux by a factor of 1.8. Collectively, these results suggest that the structure and mechanics of the CEP may play critical roles in the solute transport and disc mechanics. PMID:26874969

The effects of dynamic loading on the intervertebral disc.

PubMed

Chan, Samantha C W; Ferguson, Stephen J; Gantenbein-Ritter, Benjamin

2011-11-01

Loading is important to maintain the balance of matrix turnover in the intervertebral disc (IVD). Daily cyclic diurnal assists in the transport of large soluble factors across the IVD and its surrounding circulation and applies direct and indirect stimulus to disc cells. Acute mechanical injury and accumulated overloading, however, could induce disc degeneration. Recently, there is more information available on how cyclic loading, especially axial compression and hydrostatic pressure, affects IVD cell biology. This review summarises recent studies on the response of the IVD and stem cells to applied cyclic compression and hydrostatic pressure. These studies investigate the possible role of loading in the initiation and progression of disc degeneration as well as quantifying a physiological loading condition for the study of disc degeneration biological therapy. Subsequently, a possible physiological/beneficial loading range is proposed. This physiological/beneficial loading could provide insight into how to design loading regimes in specific system for the testing of various biological therapies such as cell therapy, chemical therapy or tissue engineering constructs to achieve a better final outcome. In addition, the parameter space of 'physiological' loading may also be an important factor for the differentiation of stem cells towards most ideally 'discogenic' cells for tissue engineering purpose.

Ultrastructure of inclusion bodies in annulus cells in the degenerating human intervertebral disc.

PubMed

Gruber, H E; Hanley, E N

2009-06-01

The rough endoplasmic reticulum (rER) of the cell has an architectural editing function that checks whether protein structure and three-dimensional assembly have occurred properly prior to export of newly synthesized material out of the cell. If these have been faulty, the material is retained within the rER as an inclusion body. Inclusion bodies have been identified previously in chondrocytes and osteoblasts in chondrodysplasias and osteogenesis imperfecta. Inclusion bodies in intervertebral disc cells, however, have only recently been recognized. Our objectives were to use transmission electron microscopy to analyze more fully inclusion bodies in the annulus pulposus and to study the extracellular matrix (ECM) surrounding cells containing inclusion bodies. ECM frequently encapsulated cells with inclusion bodies, and commonly contained prominent banded aggregates of Type VI collagen. Inclusion body material had several morphologies, including relatively smooth, homogeneous material, or a rougher, less homogeneous feature. Such findings expand our knowledge of the fine structure of the human disc cell and ECM during disc degeneration, and indicate the potential utility of ultrastructural identification of discs with intracellular inclusion bodies as a screening method for molecular studies directed toward identification of defective gene products in degenerating discs.

[Minimally invasive approach for cervical spondylotic radiculopathy].

PubMed

Ding, Liang; Sun, Taicun; Huang, Yonghui

2010-01-01

To summarize the recent minimally invasive approach for cervical spondylotic radiculopathy (CSR). The recent literature at home and abroad concerning minimally invasive approach for CSR was reviewed and summarized. There were two techniques of minimally invasive approach for CSR at present: percutaneous puncture techniques and endoscopic techniques. The degenerate intervertebral disc was resected or nucleolysis by percutaneous puncture technique if CSR was caused by mild or moderate intervertebral disc herniations. The cervical microendoscopic discectomy and foraminotomy was an effective minimally invasive approach which could provide a clear view. The endoscopy techniques were suitable to treat CSR caused by foraminal osteophytes, lateral disc herniations, local ligamentum flavum thickening and spondylotic foraminal stenosis. The minimally invasive procedure has the advantages of simple handling, minimally invasive and low incidence of complications. But the scope of indications is relatively narrow at present.

Are animal models useful for studying human disc disorders/degeneration?

PubMed Central

Eisenstein, Stephen M.; Ito, Keita; Little, Christopher; Kettler, A. Annette; Masuda, Koichi; Melrose, James; Ralphs, Jim; Stokes, Ian; Wilke, Hans Joachim

2007-01-01

Intervertebral disc (IVD) degeneration is an often investigated pathophysiological condition because of its implication in causing low back pain. As human material for such studies is difficult to obtain because of ethical and government regulatory restriction, animal tissue, organs and in vivo models have often been used for this purpose. However, there are many differences in cell population, tissue composition, disc and spine anatomy, development, physiology and mechanical properties, between animal species and human. Both naturally occurring and induced degenerative changes may differ significantly from those seen in humans. This paper reviews the many animal models developed for the study of IVD degeneration aetiopathogenesis and treatments thereof. In particular, the limitations and relevance of these models to the human condition are examined, and some general consensus guidelines are presented. Although animal models are invaluable to increase our understanding of disc biology, because of the differences between species, care must be taken when used to study human disc degeneration and much more effort is needed to facilitate research on human disc material. PMID:17632738

Human cells derived from degenerate intervertebral discs respond differently to those derived from non-degenerate intervertebral discs following application of dynamic hydrostatic pressure.

PubMed

Le Maitre, Christine Lyn; Frain, Jennie; Fotheringham, Andrew P; Freemont, Anthony J; Hoyland, Judith Alison

2008-01-01

The intervertebral disc (IVD) is one of the body's most important load-bearing structures with the major mechanical force experienced in the nucleus pulposus (NP) being hydrostatic pressure (HP). Physiological levels of HP have an anabolic effect on IVD matrix metabolism in cells derived from non-degenerate animal and herniated IVD while excessive HP has a catabolic effect. However, no studies have investigated the response of non-degenerate and degenerate human disc cells derived from non-herniated discs to HP. Here we investigate the effect of physiological HP on such cells using a novel loading rig. Human IVD cells (both NP and AF) cultured in alginate were subjected to dynamic HP (0.8-1.7 MPa 0.5 Hz) for 2 h. Cell viability was assessed, RNA extracted and qRT-PCR for 18 s, c-fos, Sox-9, collagen type II, aggrecan and MMP-3 performed. Cell viability was unaffected by the loading regime. In non-degenerate NP cells, HP increased c-fos, aggrecan, Sox-9 and collagen type II (significantly so in the case of c-fos and aggrecan), but not MMP-3 gene expression. In contrast, application of HP to AF or degenerate NP cells had no effect on target gene expression. Our data shows that cells obtained from the healthy NP respond to dynamic HP by up-regulating genes indicative of healthy matrix homeostasis. However, responses differed in degenerate NP cells suggesting that an altered mechanotransduction pathway may be operational.

Inflammatory microRNA-194 and -515 attenuate the biosynthesis of chondroitin sulfate during human intervertebral disc degeneration.

PubMed

Hu, Bo; Xu, Chen; Tian, Ye; Shi, Changgui; Zhang, Ying; Deng, Lianfu; Zhou, Hongyu; Cao, Peng; Chen, Huajiang; Yuan, Wen

2017-07-25

Intervertebral disc degeneration (IDD) is characterized by dehydration and loss of extracellular matrixes in the nucleus pulposus region. Chondroitin sulfate has been found to be the water-binding molecule that played a key role in IDD. Although investigators have reported that inflammatory cytokines are involved in the reduction of chondroitin sulfate in IDD, but the underlying mechanism is unrevealed. Since chondroitin sulfate synthesis is controlled by chondroitin sulfate glycosyltransferases CHSY-1/2/3 and CSGALNACT-1/2, their functional role and regulatory mechanism in IDD is not fully studied. Here, we set out to investigate the function and regulatory roles of these factors during IDD development. We found that among these chondroitin sulfate glycosyltransferases, CHSY-1/2/3 are significantly down-regulated in severe IDD samples than mild IDD samples. In vitro experiments revealed that Interleukin-1β and Tumor Necrosis Factor-α stimulation led to significant reduction of CHSY-1/2/3 at protein level than mRNA level in NP cells, indicating a post-transcriptional regulatory mechanisms are involved. By computational prediction and analysis, we found that inflammatory cytokines stimulated microRNA-194 and -515 target CHSY-1/2/3 mRNA and significantly interrupt their translation and downstream chondroitin sulfate deposition. Inhibition of microRNA-194 and -515 however, significantly rescued CHSY-1/2/3 expressions and chondroitin sulfate deposition. These findings together demonstrated a vital role of inflammatory stimulated microRNAs in promoting intervertebral disc degeneration by interrupt chondroitin sulfate synthesis, which may provide new insights into the mechanism and therapeutic approaches in IDD.

Hydrogels in acellular and cellular strategies for intervertebral disc regeneration.

PubMed

Pereira, D R; Silva-Correia, J; Oliveira, J M; Reis, R L

2013-02-01

Low back pain is an extremely common illness syndrome that causes patient suffering and disability and requires urgent solutions to improve the quality of life of these patients. Treatment options aimed to regenerate the intervertebral disc (IVD) are still under development. The cellular complexity of IVD, and consequently its fine regulatory system, makes it a challenge to the scientific community. Biomaterials-based therapies are the most interesting solutions to date, whereby tissue engineering and regenerative medicine (TE&RM) strategies are included. By using such strategies, i.e., combining biomaterials, cells, and biomolecules, the ultimate goal of reaching a complete integration between native and neo-tissue can be achieved. Hydrogels are promising materials for restoring IVD, mainly nucleus pulposus (NP). This study presents an overview of the use of hydrogels in acellular and cellular strategies for intervertebral disc regeneration. To better understand IVD and its functioning, this study will focus on several aspects: anatomy, pathophysiology, cellular and biomolecular performance, intrinsic healing processes, and current therapies. In addition, the application of hydrogels as NP substitutes will be addressed due to their similarities to NP mechanical properties and extracellular matrix. These hydrogels can be used in cellular strategies when combined with cells from different sources, or in acellular strategies by performing the functionalization of the hydrogels with biomolecules. In addition, a brief summary of therapies based on simple injection for primary biological repair will be examined. Finally, special emphasis will focus on reviewing original studies reporting on the use of autologous cells and biomolecules such as platelet-rich plasma and their potential clinical applications. Copyright © 2011 John Wiley & Sons, Ltd.

A minimally invasive in-fiber Bragg grating sensor for intervertebral disc pressure measurements

NASA Astrophysics Data System (ADS)

Dennison, Christopher R.; Wild, Peter M.; Wilson, David R.; Cripton, Peter A.

2008-08-01

We present an in-fiber Bragg grating (FBG) based intervertebral disc (IVD) pressure sensor that has pressure sensitivity seven times greater than that of a bare fiber, and a major diameter and sensing area of only 400 µm and 0.03 mm2, respectively. This is the only optical, the smallest and the most mechanically compliant disc pressure sensor reported in the literature. This is also an improvement over other FBG pressure sensors that achieve increased sensitivity through mechanical amplification schemes, usually resulting in major diameters and sensing lengths of many millimeters. Sensor sensitivity is predicted using numerical models, and the predicted sensitivity is verified through experimental calibrations. The sensor is validated by conducting IVD pressure measurements in porcine discs and comparing the FBG measurements to those obtained using the current standard sensor for IVD pressure. The predicted sensitivity of the FBG sensor matched with that measured experimentally. IVD pressure measurements showed excellent repeatability and agreement with those obtained from the standard sensor. Unlike the current larger sensors, the FBG sensor could be used in discs with small disc height (i.e. cervical or degenerated discs). Therefore, there is potential to conduct new measurements that could lead to new understanding of the biomechanics.

Biomarkers of Spontaneous Recovery from Traumatic Spinal Cord Injury

DTIC Science & Technology

2017-10-01

this was continued challenges with recruitment and retention, which we hope will be mitigated by our inclusion of additional sites of excellence from...Disc. Disability and pain from degenerated intervertebral discs (IVD) affects >40% of U.S adults, costs >$100 billion annually and the etiology is

Notochord-dependent expression of MFH1 and PAX1 cooperates to maintain the proliferation of sclerotome cells during the vertebral column development.

PubMed

Furumoto, T A; Miura, N; Akasaka, T; Mizutani-Koseki, Y; Sudo, H; Fukuda, K; Maekawa, M; Yuasa, S; Fu, Y; Moriya, H; Taniguchi, M; Imai, K; Dahl, E; Balling, R; Pavlova, M; Gossler, A; Koseki, H

1999-06-01

During axial skeleton development, the notochord is essential for the induction of the sclerotome and for the subsequent differentiation of cartilage forming the vertebral bodies and intervertebral discs. These functions are mainly mediated by the diffusible signaling molecule Sonic hedgehog. The products of the paired-box-containing Pax1 and the mesenchyme forkhead-1 (Mfh1) genes are expressed in the developing sclerotome and are essential for the normal development of the vertebral column. Here, we demonstrate that Mfh1 like Pax1 expression is dependent on Sonic hedgehog signals from the notochord, and Mfh1 and Pax1 act synergistically to generate the vertebral column. In Mfh1/Pax1 double mutants, dorsomedial structures of the vertebrae are missing, resulting in extreme spina bifida accompanied by subcutaneous myelomeningocoele, and the vertebral bodies and intervertebral discs are missing. The morphological defects in Mfh1/Pax1 double mutants strongly correlate with the reduction of the mitotic rate of sclerotome cells. Thus, both the Mfh1 and the Pax1 gene products cooperate to mediate Sonic hedgehog-dependent proliferation of sclerotome cells. Copyright 1999 Academic Press.

Upregulation of BDNF and NGF in cervical intervertebral discs exposed to painful whole-body vibration.

PubMed

Kartha, Sonia; Zeeman, Martha E; Baig, Hassam A; Guarino, Benjamin B; Winkelstein, Beth A

2014-09-01

In vivo study defining expression of the neurotrophins, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), in cervical intervertebral discs after painful whole-body vibration (WBV). The goal of this study is to determine if BDNF and NGF are expressed in cervical discs after painful WBV in a rat model. WBV is a possible source of neck pain and has been implicated as increasing the risk for disc disorders. Typically, aneural regions of painful human lumbar discs exhibit hyperinnervation, suggesting nerve ingrowth as potentially contributing to disc degeneration and pain. BDNF and NGF are upregulated in painfully degenerate lumbar discs and hypothesized to contribute to this pathology. Male Holtzman rats underwent 7 days of repeated WBV (15 Hz, 30 min/d) or sham exposures, followed by 7 days of rest. Cervical discs were collected for analysis of BDNF and NGF expression through RT-qPCR and Western blot analysis. Immunohistochemistry also evaluated their regional expression in the disc. Vibration significantly increases BDNF messenger ribonucleic acid (mRNA) levels (P=0.036), as well as total-NGF mRNA (P=0.035). Protein expression of both BDNF (P=0.006) and the 75-kDa NGF (P=0.045) increase by nearly 4- and 10-fold, respectively. Both BDNF mRNA (R=0.396; P=0.012) and protein (R=0.280; P=0.035) levels are significantly correlated with the degree of behavioral sensitivity (i.e., pain) at day 14. Total-NGF mRNA is also significantly correlated with the extent of behavioral sensitivity (R=0.276; P=0.044). Both neurotrophins are most increased in the inner annulus fibrosus and nucleus pulposus. The increases in BDNF and NGF in the cervical discs after painful vibration are observed in typically aneural regions of the disc, consistent with reports of its hyperinnervation. Yet, the induction of nerve ingrowth into the disc was not explicitly investigated. Neurotrophin expression also correlates with behavioral sensitivity, suggesting a role for both neurotrophins in the development of disc pain. N/A.

Evaluation of intervertebral disc regeneration with implantation of bone marrow mesenchymal stem cells (BMSCs) using quantitative T2 mapping: a study in rabbits.

PubMed

Cai, Feng; Wu, Xiao-Tao; Xie, Xin-Hui; Wang, Feng; Hong, Xin; Zhuang, Su-Yang; Zhu, Lei; Rui, Yun-Feng; Shi, Rui

2015-01-01

The aim of the study was to investigate the curative effects of transplantation of bone marrow mesenchymal stem cells (BMSCs) on intervertebral disc regeneration and to investigate the feasibility of the quantitative T2 mapping method for evaluating repair of the nucleus pulposus after implantation of BMSCs. Forty-eight New Zealand white rabbits were used to establish the lumber disc degenerative model by stabbing the annulus fibrosus and then randomly divided into four groups, i.e. two weeks afterwards, BMSCs or phosphate-buffered saline (PBS) were transplanted into degenerative discs (BMSCs group and PBS group), while the operated rabbits without implantation of BMSCs or PBS served as the sham group and the rabbits without operation were used as the control group. At weeks two, six and ten after operation, the T2 values and disc height indices (DHI) were calculated by magnetic resonance imaging (MRI 3.0 T), and the gene expressions of type II collagen (COL2) and aggrecan (ACAN) in degenerative discs were evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR). T2 values for the nucleus pulposus were correlated with ACAN or COL2 expression by regression analysis. Cell clusters, disorganised fibres, interlamellar glycosaminoglycan (GAG) matrix and vascularisation were observed in lumber degenerative discs. BMSCs could be found to survive in intervertebral discs and differentiate into nucleus pulposus-like cells expressing COL2 and ACAN. The gene expression of COL2 and ACAN increased during ten weeks after transplantation as well as the T2 signal intensity and T2 value. The DHI in the BMSCs group decreased more slowly than that in PBS and sham groups. The T2 value correlated significantly with the gene expression of ACAN and COL2 in the nucleus pulposus. Transplantation of BMSCs was able to promote the regeneration of degenerative discs. Quantitative and non-invasive T2 mapping could be used to evaluate the regeneration of the nucleus pulposus with good sensitivity.

Stress in Lumbar Intervertebral Discs during Distraction

PubMed Central

Gay, Ralph E.; Ilharreborde, Brice; Zhao, Kristin D.; Berglund, Lawrence J.; Bronfort, Gert; An, Kai-Nan

2008-01-01

BACKGROUND CONTEXT The intervertebral disc is a common source of low back pain. Prospective studies suggest that treatments that intermittently distract the disc might be beneficial for chronic low back pain. Although the potential exists for distraction therapies to affect the disc biomechanically their effect on intradiscal stress is debated. PURPOSE To determine if distraction alone, distraction combined with flexion or distraction combined with extension can reduce nucleus pulposus pressure and posterior anulus compressive stress in cadaveric lumbar discs compared to simulated standing or lying. STUDY DESIGN Laboratory study using single cadaveric motion segments. OUTCOME MEASURES Strain gauge measures of nucleus pulposus pressure and compressive stress in the anterior and posterior annulus fibrosus METHODS Intradiscal stress profilometry was performed on 15 motion segments during 5 simulated conditions: standing, lying, and 3 distracted conditions. Disc degeneration was graded by inspection from 1 (normal) to 4 (severe degeneration). RESULTS All distraction conditions markedly reduced nucleus pressure compared to either simulated standing or lying. There was no difference between distraction with flexion and distraction with extension in regard to posterior annulus compressive stress. Discs with little or no degeneration appeared to distributed compressive stress differently than those with moderate or severe degeneration. CONCLUSIONS Distraction appears to predictably reduce nucleus pulposus pressure. The effect of distraction therapy on the distribution of compressive stress may be dependent in part on the health of the disc. PMID:17981092

Low Intensity Pulsed Ultrasound (LIPUS) for the treatment of intervertebral disc degeneration

NASA Astrophysics Data System (ADS)

Horne, Devante; Jones, Peter; Salgaonkar, Vasant; Adams, Matt; Ozilgen, B. Arda; Zahos, Peter; Tang, Xinyan; Liebenberg, Ellen; Coughlin, Dezba; Lotz, Jeffrey; Diederich, Chris

2017-02-01

Discogenic back pain presents a major public health issue, with current therapeutic interventions limited to short-term symptom relief without providing regenerative remedies for diseased intervertebral discs (IVD). Many of these interventions are invasive and can diminish the biomechanical integrity of the IVDs. Low intensity pulsed ultrasound (LIPUS) is a potential treatment option that is both non-invasive and regenerative. LIPUS has been shown to be a clinically effective method for the enhancement of wound and fracture healing. Recent in vitro studies have shown that LIPUS stimulation induces an upregulation functional matrix proteins and downregulation of inflammatory factors in cultured IVD cells. However, we do not know the effects of LIPUS on an in vivo model for intervertebral disc degeneration. The objective of this study was to show technical feasibility of building a LIPUS system that can target the rat tail IVD and apply this setup to a model for acute IVD degeneration. A LIPUS exposimetry system was built using a 1.0 MHz planar transducer and custom housing. Ex vivo intensity measurements demonstrated LIPUS delivery to the center of the rat tail IVD. Using an established stab-incision model for disc degeneration, LIPUS was applied for 20 minutes daily for five days. For rats that displayed a significant injury response, LIPUS treatment caused significant upregulation of Collagen II and downregulation of Tumor Necrosis Factor - α gene expression. Our preliminary studies indicate technical feasibility of targeted delivery of ultrasound to a rat tail IVD for studies of LIPUS biological effects.

Prevalence and geographic distribution of herniated intervertebral disc in Korean 19-year-old male from 2008 to 2009: a study based on Korean conscription -national and geographic prevalence of herniated intervertebral disc in Korean 19YO male-.

PubMed

Lee, Sang Hun; Oh, Chang Hyun; Yoon, Seung Hwan; Park, Hyeong-chun; Park, Chong Oon

2013-09-01

This study was to determine the prevalence of herniated intervertebral disc (HIVD) among Korean 19-year-old male in a large national sample and to compare the prevalence across geographic regions based on the data of conscription. We analyzed the conscription data of 615508 cases who were 19-year-old male, given an examination for conscription at nationwide Korean Military Manpower Administration from January 2008 to December 2009. Prevalence was determined by dividing the number of cases by the number of persons enrolled for 2 years. The analyses included of a cross-tabulations and nonparametric chi-square to compare the prevalence according to geographic region, disc severity, and conscription year. The prevalence of HIVD among 19-year-old male was 0.47%. Seoul had the highest prevalence of HIVD (total HIVD was 0.60%, and severe HIVD was 0.44%). The prevalence of HIVD was lower in Jeollabuk- do and Jeollanam-do (total HIVD was 0.25-0.27%, and severe HIVD was 0.16-0.17%). Annual prevalence of HIVD was slightly decreased in 2009, but geographic distribution annually was not different. In Korean 19-year-old male, the national prevalence of adolescent HIVD was 0.60%, but different geographic distribution was observed. It is quite possible that secondary contributing factor(s) interfere with the different geographic prevalence of HIVD.

Chemometric evaluation of concentrations of trace elements in intervertebral disc tissue in patient with degenerative disc disease.

PubMed

Kubaszewski, Łukasz; Zioła-Frankowska, Anetta; Gasik, Zuzanna; Frankowski, Marcin; Dąbrowski, Mikołaj; Molisak, Bartłomiej; Kaczmarczyk, Jacek; Gasik, Robert

2017-12-23

The work is designed to uncover the pattern of mutual relation among trace elements and epidemiological data in the degenerated intervertebral disk tissue in humans. Hitherto the reason of the degenerative process is not fully understood. Trace elements are the basic components of the biological compound related both its metabolism as well as environmental exposure. The relation pattern among elements occurs gives new perspective in solving the cause of the disease. We have analysed trace elements content in the 30 intervertebral disc from 22 patients with degenerative disc disease. The concentrations of Al, Cu, Cd, Mo, Ni and Pb were determined with Atomic Absorption Spectrometry. To analyse the multidimentional relation between trace element concentration and epidemiological data the chemometric analysis was applied. The similarity have been shown in occurrence of following pairs: Cd-Mo as well as Mg-Zn. The second pair was correlated with Pb concentration. Pb levels are observed to be competitive to Cu concentration. Cd concentration was related to Zn and Mg deficiency. No single but rather cluster of epidemiological data show observable influence on the TE tissue variance. Zn and Cu was related to the male sex. Operation with orthopedic implants were related to combined Al, Mo and Zn concentration. This is the first chemometric analysis of trace elements in disk tissue. It shows multidimentional relations that are missed by the classical statistic. The analysis shows significant relation. The nature of the relations is the basis for further metabolic and environmental research.

Why do some intervertebral discs degenerate, when others (in the same spine) do not?

PubMed

Adams, Michael A; Lama, Polly; Zehra, Uruj; Dolan, Patricia

2015-03-01

This review suggests why some discs degenerate rather than age normally. Intervertebral discs are avascular pads of fibrocartilage that allow movement between vertebral bodies. Human discs have a low cell density and a limited ability to adapt to mechanical demands. With increasing age, the matrix becomes yellowed, fibrous, and brittle, but if disc structure remains intact, there is little impairment in function, and minimal ingrowth of blood vessels or nerves. Approximately half of old lumbar discs degenerate in the sense of becoming physically disrupted. The posterior annulus and lower lumbar discs are most affected, presumably because they are most heavily loaded. Age and genetic inheritance can weaken discs to such an extent that they are physically disrupted during everyday activities. Damage to the endplate or annulus typically decompresses the nucleus, concentrates stress within the annulus, and allows ingrowth of nerves and blood vessels. Matrix disruption progresses by mechanical and biological means. The site of initial damage leads to two disc degeneration "phenotypes": endplate-driven degeneration is common in the upper lumbar and thoracic spine, and annulus-driven degeneration is common at L4-S1. Discogenic back pain can be initiated by tissue disruption, and amplified by inflammation and infection. Healing is possible in the outer annulus only, where cell density is highest. We conclude that some discs degenerate because they are disrupted by excessive mechanical loading. This can occur without trauma if tissues are weakened by age and genetic inheritance. Moderate mechanical loading, in contrast, strengthens all spinal tissues, including discs. © 2014 Wiley Periodicals, Inc.

Intervertebral disc biomechanical analysis using the finite element modeling based on medical images.

PubMed

Li, Haiyun; Wang, Zheng

2006-01-01

In this paper, a 3D geometric model of the intervertebral and lumbar disks has been presented, which integrated the spine CT and MRI data-based anatomical structure. Based on the geometric model, a 3D finite element model of an L1-L2 segment was created. Loads, which simulate the pressure from above were applied to the FEM, while a boundary condition describing the relative L1-L2 displacement is imposed on the FEM to account for 3D physiological states. The simulation calculation illustrates the stress and strain distribution and deformation of the spine. The method has two characteristics compared to previous studies: first, the finite element model of the lumbar are based on the data directly derived from medical images such as CTs and MRIs. Second, the result of analysis will be more accurate than using the data of geometric parameters. The FEM provides a promising tool in clinical diagnosis and for optimizing individual therapy in the intervertebral disc herniation.

Human cartilage endplate permeability varies with degeneration and intervertebral disc site.

PubMed

DeLucca, John F; Cortes, Daniel H; Jacobs, Nathan T; Vresilovic, Edward J; Duncan, Randall L; Elliott, Dawn M

2016-02-29

Despite the critical functions the human cartilage endplate (CEP) plays in the intervertebral disc, little is known about its structural and mechanical properties and their changes with degeneration. Quantifying these changes with degeneration is important for understanding how the CEP contributes to the function and pathology of the disc. Therefore the objectives of this study were to quantify the effect of disc degeneration on human CEP mechanical properties, determine the influence of superior and inferior disc site on mechanics and composition, and simulate the role of collagen fibers in CEP and disc mechanics using a validated finite element model. Confined compression data and biochemical composition data were used in a biphasic-swelling model to calculate compressive extrafibrillar elastic and permeability properties. Tensile properties were obtained by applying published tensile test data to an ellipsoidal fiber distribution. Results showed that with degeneration CEP permeability decreased 50-60% suggesting that transport is inhibited in the degenerate disc. CEP fibers are organized parallel to the vertebrae and nucleus pulposus and may contribute to large shear strains (0.1-0.2) and delamination failure of the CEP commonly seen in herniated disc tissue. Fiber-reinforcement also reduces CEP axial strains thereby enhancing fluid flux by a factor of 1.8. Collectively, these results suggest that the structure and mechanics of the CEP may play critical roles in the solute transport and disc mechanics. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Finite element analysis of lumbar pelvic and proximal femur model with simulate lumbar rotatory manipulation].

PubMed

Hu, Hua; Xiong, Chang-Yuan; Han, Guo-Wu

2012-07-01

To study the changes of displacement and stress in the model of lumbar pelvic and proximal femur during lumbar rotatory manipulation. The date of lumbar pelvic and proximal femur CT scan by Mimics 10.01 software was established a lumbar pelvic and proximal femur geometric model, then the model was modified with Geomagic 9, at last the modified model was imported into hypermesh 10 and meshed with tetrahedron, at the same time,add disc and ligaments. According to the principle of lumbar rotatory manipulation,the lumbar rotatory manipulation were decomposed. The mechanical parameters assigned into the three-dimensional finite element model. The changes of displacement and stress in the model of lunbar pelvic and proximal femur under the four conditions were calculated with Abaqus model of Hypermesh 10. 1) Under the same condition,the displacement order of lumbar was L1>L2>L3>L5 L5, anterior column > middle column > posterior column. 2) Under the different conditions, the displacement order of lumbar,case 3>case 1>case 4>case 2. 3) Under the same conditions, the displacement order of lumbar inter-vertebral disc from L1,2 to L5S1 was L1,2>L2,3>L3,4>L4,5>L5S1, as for the same inter-vertebral disc, the order was: second quadrant>third quadrant>first quadrant>fourth quadrant. 4) Under the different conditions,the displacement order of the inter-vertebral disc was L1,2>L2,3>L3,4>L4,5>L5S1, but to same inter-vertebral disc: case 3>case 4>case 1 >case 2. 5) There were apparent displacement and stress concentration in pelvis and hip during the manipulation. 1) The principles of lumbar rotation manipulation closely related to the relative displacement caused by rotation of various parts of lumbar pelvic and proximal femur model; 2) During the process of lumbar rotatory manipulation, the angle of lateral bending and flexion can not be randomly increased; 3) During the process of lumbar rotatory manipulation, all the conditions of lumbar pelvic and proximal femur must be considered to determine indications and contraindications.

Sirtuin 6 prevents matrix degradation through inhibition of the NF-κB pathway in intervertebral disc degeneration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kang, Liang; Hu, Jia; Weng, Yuxiong

Intervertebral disc degeneration (IDD) is marked by imbalanced metabolism of the extracellular matrix (ECM) in the nucleus pulposus (NP) of intervertebral discs. This study aimed to determine whether sirtuin 6 (SIRT6), a member of the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases, protects the NP from ECM degradation in IDD. Our study showed that expression of SIRT6 markedly decreased during IDD progression. Overexpression of wild-type SIRT6, but not a catalytically inactive mutant, prevented IL-1β-induced NP ECM degradation. SIRT6 depletion by RNA interference in NP cells caused ECM degradation. Moreover, SIRT6 physically interacted with nuclear factor-κB (NF-κB) catalytic subunit p65, transcriptionalmore » activity of which was significantly suppressed by SIRT6 overexpression. These results suggest that SIRT6 prevented NP ECM degradation in vitro via inhibiting NF-κB-dependent transcriptional activity and that this effect depended on its deacetylase activity. - Highlights: • SIRT6 expression is decreased in degenerative nucleus pulposus (NP) tissues. • SIRT6 overexpression lowers IL-1β-induced matrix degradation of NP. • SIRT6 inhibition induces matrix degradation of NP. • SIRT6 prevents matrix degradation of NP via the NF-κB signaling pathway.« less

Role of load history in intervertebral disc mechanics and intradiscal pressure generation.

PubMed

Hwang, David; Gabai, Adam S; Yu, Miao; Yew, Alvin G; Hsieh, Adam H

2012-01-01

Solid-fluid interactions play an important role in mediating viscoelastic behaviour of biological tissues. In the intervertebral disc, water content is governed by a number of factors, including age, disease and mechanical loads, leading to changes in stiffness characteristics. We hypothesized that zonal stress distributions depend on load history, or the prior stresses experienced by the disc. To investigate these effects, rat caudal motion segments were subjected to compressive creep biomechanical testing in vitro using a protocol that consisted of two phases: a Prestress Phase (varied to represent different histories of load) followed immediately by an Exertion Phase, identical across all Prestress groups. Three analytical models were used to fit the experimental data in order to evaluate load history effects on gross and zonal disc mechanics. Model results indicated that while gross transient response was insensitive to load history, there may be changes in the internal mechanics of the disc. In particular, a fluid transport model suggested that the role of the nucleus pulposus in resisting creep during Exertion depended on Prestress conditions. Separate experiments using similarly defined load history regimens were performed to verify these predictions by measuring intradiscal pressure with a fibre optic sensor. We found that the ability for intradiscal pressure generation was load history-dependent and exhibited even greater sensitivity than predicted by analytical models. A 0.5 MPa Exertion load resulted in 537.2 kPa IDP for low magnitude Prestress compared with 373.7 kPa for high magnitude Prestress. Based on these measurements, we developed a simple model that may describe the pressure-shear environment in the nucleus pulposus. These findings may have important implications on our understanding of how mechanical stress contributes to disc health and disease etiology.

[The "window" surgical exposure strategy of the upper anterior cervical retropharyngeal approach for anterior decompression at upper cervical spine].

PubMed

Wu, Xiang-Yang; Zhang, Zhe; Wu, Jian; Lü, Jun; Gu, Xiao-Hui

2009-11-01

To investigate the "window" surgical exposure strategy of the upper anterior cervical retropharyngeal approach for the exposure and decompression and instrumentation of the upper cervical spine. From Jan. 2000 to July 2008, 5 patients with upper cervical spinal injuries were treated by surgical operation included 4 males and 1 female with and average age of 35 years old ranging from 16 to 68 years. There were 2 cases of Hangman's fractures (type II ), 2 of C2.3 intervertebral disc displacement and 1 of C2 vertebral body tuberculosis. All patients underwent the upper cervical anterior retropharyngeal approach through the "window" between the hypoglossal nerve and the superior laryngeal nerve and pharynx and carotid artery. Two patients of Hangman's fractures underwent the C2,3 intervertebral disc discectomy, bone graft fusion and internal fixation. Two patients of C2,3 intervertebral disc displacement underwent the C2,3 intervertebral disc discectomy, decompression bone graft fusion and internal fixation. One patient of C2 vertebral body tuberculosis was dissected and resected and the focus and the cavity was filled by bone autografting. C1 anterior arch to C3 anterior vertebral body were successful exposed. Lesion resection or decompression and fusion were successful in all patients. All patients were followed-up for from 5 to 26 months (means 13.5 months). There was no important vascular and nerve injury and no wound infection. Neutral symptoms was improved and all patient got successful fusion. The "window" surgical exposure surgical technique of the upper cervical anterior retropharyngeal approach is a favorable strategy. This approach strategy can be performed with full exposure for C1-C3 anterior anatomical structure, and can get minimally invasive surgery results and few and far between wound complication, that is safe if corresponding experience is achieved.

In vivo effects of bupivacaine and gadobutrol on the intervertebral disc following discoblock and discography: a histological analysis.

PubMed

Strube, Patrick; Pfitzner, Berit M; Streitparth, Florian; Hartwig, Tony; Putzier, Michael

2017-01-01

The aim of the present study was to histologically compare chondrotoxicity in surgically harvested intervertebral discs (IVDs) of patients following discoblock, discography, or no preoperative intervention. Thirty patients (IVD degeneration Modic ≥ 2°, Pfirrmann 3° or 4°) at L4/5 or L5/S1 who were planned for anterior lumbar interbody fusion were randomly assigned to three groups (open MRI: group DG - discography with gadobutrol; group DB - discoblock with bupivacaine at 4 weeks prior to surgery; group C - no intervention). The intervertebral discs were histologically evaluated and compared using ANOVA and Bonferroni tests for cell count, apoptosis, and proliferation. A reduced cell count (groups DG vs. DB vs. C: 14.9 ± 7.1, 9.2 ± 3.8, and 16.6 ± 5.2 cells/mm 2 , respectively; p ANOVA  = 0.016), increased apoptosis (groups DG vs. DB vs. C: 34.9 ± 10.2, 47.4 ± 16.3, 32.6 ± 12.2 %, respectively; p ANOVA  = 0.039) and increased cell proliferation (post hoc pDB vs. DG or C p < 0.001; for 3-7 cell monoclonal cell nests: groups DG vs. DB vs. C: 2.4 ± 1, 3.9 ± 1, 2.2 ± 1.1, respectively; p intervention x nest size  = 0.006) were found in the IVDs of patients in group DB. This in vivo study suggests that chondrotoxic effects occur in IVD cells after the intradiscal injection of bupivacaine but not after gadobutrol administration. • Local bupivacaine administration to intervertebral discs leads to cell toxicity and proliferation. • Gadobutrol demonstrated no significant effect on cell count, apoptosis, or cell proliferation. • In vivo cytotoxicity was demonstrated histologically in humans for the first time. • Addition/administration of bupivacaine during discographies must be judged critically.

Exosomes as potential alternatives to stem cell therapy for intervertebral disc degeneration: in-vitro study on exosomes in interaction of nucleus pulposus cells and bone marrow mesenchymal stem cells.

PubMed

Lu, Kang; Li, Hai-Yin; Yang, Kuang; Wu, Jun-Long; Cai, Xiao-Wei; Zhou, Yue; Li, Chang-Qing

2017-05-10

The stem cell-based therapies for intervertebral disc degeneration have been widely studied. However, the mechanisms of mesenchymal stem cells interacting with intervertebral disc cells, such as nucleus pulposus cells (NPCs), remain unknown. Exosomes as a vital paracrine mechanism in cell-cell communication have been highly focused on. The purpose of this study was to detect the role of exosomes derived from bone marrow mesenchymal stem cells (BM-MSCs) and NPCs in their interaction with corresponding cells. The exosomes secreted by BM-MSCs and NPCs were purified by differential centrifugation and identified by transmission electron microscope and immunoblot analysis of exosomal marker proteins. Fluorescence confocal microscopy was used to examine the uptake of exosomes by recipient cells. The effects of NPC exosomes on the migration and differentiation of BM-MSCs were determined by transwell migration assays and quantitative RT-PCR analysis of NPC phenotypic genes. Western blot analysis was performed to examine proteins such as aggrecan, sox-9, collagen II and hif-1α in the induced BM-MSCs. Proliferation and the gene expression profile of NPCs induced by BM-MSC exosomes were measured by Cell Counting Kit-8 and qRT-PCR analysis, respectively. Both the NPCs and BM-MSCs secreted exosomes, and these exosomes underwent uptake by the corresponding cells. NPC-derived exosomes promoted BM-MSC migration and induced BM-MSC differentiation to a nucleus pulposus-like phenotype. BM-MSC-derived exosomes promoted NPC proliferation and healthier extracellular matrix production in the degenerate NPCs. Our study indicates that the exosomes act as an important vehicle in information exchange between BM-MSCs and NPCs. Given a variety of functions and multiple advantages, exosomes alone or loaded with specific genes and drugs would be an appropriate option in a cell-free therapy strategy for intervertebral disc degeneration.

Alterations in intervertebral disc composition, matrix homeostasis and biomechanical behavior in the UCD-T2DM rat model of type 2 diabetes

PubMed Central

Fields, Aaron J.; Berg-Johansen, Britta; Metz, Lionel N.; Miller, Stephanie; La, Brandan; Liebenberg, Ellen C.; Coughlin, Dezba G.; Graham, James L.; Stanhope, Kimber L.; Havel, Peter J.; Lotz, Jeffrey C.

2015-01-01

Type 2 diabetes (T2D) adversely affects many tissues, and the greater incidence of discogenic low back pain among diabetic patients suggests that the intervertebral disc is affected too. Using a rat model of polygenic obese T2D, we demonstrate that diabetes compromises several aspects of disc composition, matrix homeostasis and biomechanical behavior. Coccygeal motion segments were harvested from 6-month-old lean Sprague-Dawley rats, obese Sprague-Dawley rats, and diabetic obese UCD-T2DM rats (diabetic for 69 ± 7 days). Findings indicated that diabetes but not obesity reduced disc glycosaminoglycan and water contents, and these degenerative changes correlated with increased vertebral endplate thickness and decreased endplate porosity, and with higher levels of the advanced glycation end-product (AGE) pentosidine. Consistent with their diminished glycosaminoglycan and water contents and their higher AGE levels, discs from diabetic rats were stiffer and exhibited less creep when compressed. At the matrix level, elevated expression of hypoxia-inducible genes and catabolic markers in the discs from diabetic rats coincided with increased oxidative stress and greater interactions between AGEs and one of their receptors (RAGE). Taken together, these findings indicate that endplate sclerosis, increased oxidative stress and AGE/RAGE-mediated interactions could be important factors for explaining the greater incidence of disc pathology in T2D. PMID:25641259

[Study on the effect of vertebrae semi-dislocation on the stress distribution in facet joint and interuertebral disc of patients with cervical syndrome based on the three dimensional finite element model].

PubMed

Zhang, Ming-cai; Lü, Si-zhe; Cheng, Ying-wu; Gu, Li-xu; Zhan, Hong-sheng; Shi, Yin-yu; Wang, Xiang; Huang, Shi-rong

2011-02-01

To study the effect of vertebrae semi-dislocation on the stress distribution in facet joint and interuertebral disc of patients with cervical syndrome using three dimensional finite element model. A patient with cervical spondylosis was randomly chosen, who was male, 28 years old, and diagnosed as cervical vertebra semidislocation by dynamic and static palpation and X-ray, and scanned from C(1) to C(7) by 0.75 mm slice thickness of CT. Based on the CT data, the software was used to construct the three dimensional finite element model of cervical vertebra semidislocation (C(4)-C(6)). Based on the model,virtual manipulation was used to correct the vertebra semidislocation by the software, and the stress distribution was analyzed. The result of finite element analysis showed that the stress distribution of C(5-6) facet joint and intervertebral disc changed after virtual manipulation. The vertebra semidislocation leads to the abnormal stress distribution of facet joint and intervertebral disc.

Distinction between the extracellular matrix of the nucleus pulposus and hyaline cartilage: a requisite for tissue engineering of intervertebral disc.

PubMed

Mwale, F; Roughley, P; Antoniou, J

2004-12-15

Tissue engineering of intervertebral discs (IVD) using mesenchymal stem cells (MSCs) induced to differentiate into a disc-cell phenotype has been considered as an alternative treatment for disc degeneration. However, since there is no unique marker characteristic of discs and since hyaline cartilage and immature nucleus pulposus (NP) possess similar macromolecules in their extracellular matrix, it is currently difficult to recognize MSC conversion to a disc cell. This study was performed to compare the proteoglycan to collagen ratio (measured as GAG to hydroxyproline ratio) in the NP of normal disc to that of the hyaline cartilage of the endplate within the same group of individuals and test the hypothesis that this ratio can be used for in vivo studies to distinguish between a normal NP and hyaline cartilage phenotype. Whole human lumbar spine specimens from fresh cadavers, ranging in age from 12 weeks to 79 years, were used to harvest the IVDs and adjacent endplates. The GAG to hydroxyproline ratio within the NP of young adults is approximately 27:1, whereas the ratio within the hyaline cartilage endplate of the same aged individuals is about 2:1. The production of an extracellular matrix with a high proteoglycan to collagen ratio can be used in vivo to distinguish NP cells from chondrocytes, and could help in identifying a NP-like phenotype in vivo as opposed to a chondrocyte when MSCs are induced to differentiate for tissue engineering of a disc.

Reduced Nucleus Pulposus Glycosaminoglycan Content Alters Intervertebral Disc Dynamic Viscoelastic Mechanics

PubMed Central

Boxberger, John I.; Orlansky, Amy S.; Sen, Sounok; Elliott, Dawn M.

2009-01-01

The intervertebral disc functions over a range of dynamic loading regimes including axial loads applied across a spectrum of frequencies at varying compressive loads. Biochemical changes occurring in early degeneration, including reduced nucleus pulposus glycosaminoglycan content, may alter disc mechanical behavior and thus may contribute to the progression of degeneration. The objective of this study was to determine disc dynamic viscoelastic properties under several equilibrium loads and loading frequencies, and further, to determine how reduced nucleus glycosaminglycan content alters dynamic mechanics. We hypothesized (1) that dynamic stiffness would be elevated with increasing equilibrium load and increasing frequency, (2) that the disc would behave more elastically at higher frequencies, and finally, (3) that dynamic stiffness would be reduced at low equilibrium loads under all frequencies due to nucleus glycosaminoglycan loss. We mechanically tested control and chondroitinase-ABC injected rat lumbar motion segments at several equilibrium loads using oscillatory loading at frequencies ranging from 0.05 to 5 Hz. The rat lumbar disc behaved non-linearly with higher dynamic stiffness at elevated compressive loads irrespective of frequency. Phase angle was not affected by equilibrium load, although it decreased as frequency was increased. Reduced glycosaminoglycan decreased dynamic stiffness at low loads but not at high equilibrium loads and led to increased phase angle at all loads and frequencies. The findings of this study demonstrate the effect of equilibrium load and loading frequencies on dynamic disc mechanics and indicate possible mechanical mechanisms through which disc degeneration can progress. PMID:19539936

Regional variations in the density and arrangement of elastic fibres in the anulus fibrosus of the human lumbar disc

PubMed Central

Smith, Lachlan J; Fazzalari, Nicola L

2006-01-01

Elastic fibres are critical components of the extracellular matrix in dynamic biological structures that undergo extension and recoil. Their presence has been demonstrated in the anulus fibrosus of the human lumbar intervertebral disc; however, a detailed regional analysis of their density and arrangement has not been undertaken, limiting our understanding of their structural and functional roles. In this investigation we have quantitatively described regional variations in elastic fibre density in the anulus fibrosus of the human L3–L4 intervertebral disc using histochemistry and light microscopy. Additionally, a multiplanar comparison of patterns of elastic fibre distribution in the intralamellar and interlamellar zones was undertaken. Novel imaging techniques were developed to facilitate the visualization of elastic fibres otherwise masked by dense surrounding matrix. Elastic fibre density was found to be significantly higher in the lamellae of the posterolateral region of the anulus than the anterolateral, and significantly higher in the outer regions than the inner, suggesting that elastic fibre density in each region of the anulus is commensurate with the magnitude of the tensile deformations experienced in bending and torsion. Elastic fibre arrangments in intralamellar and interlamellar zones were shown to be architecturally distinct, suggesting that they perform multiple functional roles within the anulus matrix structural hierarchy. PMID:16928204

Lactoferricin enhances BMP7-stimulated anabolic pathways in intervertebral disc cells.

PubMed

Ellman, Michael B; Kim, Jaesung; An, Howard S; Chen, Di; Kc, Ranjan; Li, Xin; Xiao, Guozhi; Yan, Dongyao; Suh, Joon; van Wjnen, Andre J; Wang, James H-C; Kim, Su-Gwan; Im, Hee-Jeong

2013-07-25

Bone-morphogenetic protein-7 (BMP7) is a well-known anabolic and anti-catabolic growth factor on intervertebral disc (IVD) matrix and cell homeostasis. Similarly, Lactoferricin B (LfcinB) has recently been shown to have pro-anabolic, anti-catabolic, anti-oxidative and/or anti-inflammatory effects in bovine disc cells in vitro. In this study, we investigated the potential benefits of using combined peptide therapy with LfcinB and BMP7 for intervertebral disc matrix repair and to understand cellular and signaling mechanisms controlled by these factors. We studied the effects of BMP7 and LfcinB as individual treatments and combined therapy on bovine nucleus pulposus (NP) cells by assessing proteoglycan (PG) accumulation and synthesis, and the gene expression of matrix protein aggrecan and transcription factor SOX-9. We also analyzed the role of Noggin, a BMP antagonist, in IVD tissue and examined its effect after stimulation with LfcinB. To understand the molecular mechanisms by which LfcinB synergizes with BMP7, we investigated the ERK-SP1 axis as a downstream intracellular signaling regulator involved in BMP7 and LfcinB-mediated activities. Treatment of bovine NP cells cultured in alginate with LfcinB plus BMP7 synergistically stimulates PG synthesis and accumulation in part by upregulation of aggrecan gene expression. The synergism results from LfcinB-mediated activation of Sp1 and SMAD signaling pathways by (i) phosphorylation of SMAD 1/5/8; (ii) downregulation of SMAD inhibitory factors [i.e., noggin and SMAD6 (inhibitory SMAD)]; and (iii) upregulation of SMAD4 (universal co-SMAD). These data indicate that LfcinB-suppression of Noggin may eliminate the negative feedback of BMP7, thereby maximizing biological activity of BMP7 and ultimately shifting homeostasis to a pro-anabolic state in disc cells. We propose that combination growth factor therapy using BMP7 and LfcinB may be beneficial for treatment of disc degeneration. Copyright © 2013 Elsevier B.V. All rights reserved.

Disc cell clusters in pathological human intervertebral discs are associated with increased stress protein immunostaining.

PubMed

Sharp, Christopher A; Roberts, Sally; Evans, Helena; Brown, Sharon J

2009-11-01

Intervertebral disc (IVD) cells within the annulus fibrosus (AF) and nucleus pulposus (NP) maintain distinct functional extracellular matrices and operate within a potentially noxious and stressful environment. How disc cells respond to stress and whether stress is responsible for triggering degeneration is unknown. Disc cell proliferation and cluster formation are most marked in degenerate IVDs, possibly indicating attempts at matrix repair. In other tissues, stress proteins increase rapidly after stress protecting cell function and, although implicated in degeneration of articular cartilage, have received little attention in degenerative IVD pathologies. We have compared the distribution of stress protein immunolocalization in pathological and control IVDs. Disc tissues were obtained at surgery from 43 patients with degenerative disc disease (DDD) and herniation, and 12 controls at postmortem. Tissues were immunostained with a polyclonal antibody for heat shock factor 1 (HSF-1) and monoclonal antibodies for the heat shock proteins, Hsp27 and Hsp72, using an indirect immunoperoxidase method. Positively stained cells were expressed as a percentage of the total. Cell cluster formation was also assessed. The proportion of cells in clusters was similar in the AF (both 2%) and NP (8 and 9%) of control and DDD samples, whereas in herniated tissues this was increased (AF 12%, NP 14%). Stress antigen staining tended to be more frequent in clustered rather than in single/doublet cells, and this was significant (P < 0.005) in both the AF and NP of herniated discs. Clustered cells, which are most common in herniated discs, may be mounting a protective response to abnormal environmental factors associated with disc degeneration. A better understanding of the stress response in IVD cells may allow its utilization in disc cell therapies.

Integrating MRI-based geometry, composition and fiber architecture in a finite element model of the human intervertebral disc.

PubMed

Stadelmann, Marc A; Maquer, Ghislain; Voumard, Benjamin; Grant, Aaron; Hackney, David B; Vermathen, Peter; Alkalay, Ron N; Zysset, Philippe K

2018-05-17

Intervertebral disc degeneration is a common disease that is often related to impaired mechanical function, herniations and chronic back pain. The degenerative process induces alterations of the disc's shape, composition and structure that can be visualized in vivo using magnetic resonance imaging (MRI). Numerical tools such as finite element analysis (FEA) have the potential to relate MRI-based information to the altered mechanical behavior of the disc. However, in terms of geometry, composition and fiber architecture, current FE models rely on observations made on healthy discs and might therefore not be well suited to study the degeneration process. To address the issue, we propose a new, more realistic FE methodology based on diffusion tensor imaging (DTI). For this study, a human disc joint was imaged in a high-field MR scanner with proton-density weighted (PD) and DTI sequences. The PD image was segmented and an anatomy-specific mesh was generated. Assuming accordance between local principal diffusion direction and local mean collagen fiber alignment, corresponding fiber angles were assigned to each element. Those element-wise fiber directions and PD intensities allowed the homogenized model to smoothly account for composition and fibrous structure of the disc. The disc's in vitro mechanical behavior was quantified under tension, compression, flexion, extension, lateral bending and rotation. The six resulting load-displacement curves could be replicated by the FE model, which supports our approach as a first proof of concept towards patient-specific disc modeling. Copyright © 2018 Elsevier Ltd. All rights reserved.

Nonlinear dynamics of the human lumbar intervertebral disc.

PubMed

Marini, Giacomo; Huber, Gerd; Püschel, Klaus; Ferguson, Stephen J

2015-02-05

Systems with a quasi-static response similar to the axial response of the intervertebral disc (i.e. progressive stiffening) often present complex dynamics, characterized by peculiar nonlinearities in the frequency response. However, such characteristics have not been reported for the dynamic response of the disc. The accurate understanding of disc dynamics is essential to investigate the unclear correlation between whole body vibration and low back pain. The present study investigated the dynamic response of the disc, including its potential nonlinear response, over a range of loading conditions. Human lumbar discs were tested by applying a static preload to the top and a sinusoidal displacement at the bottom of the disc. The frequency of the stimuli was set to increase linearly from a low frequency to a high frequency limit and back down. In general, the response showed nonlinear and asymmetric characteristics. For each test, the disc had different response in the frequency-increasing compared to the frequency-decreasing sweep. In particular, the system presented abrupt changes of the oscillation amplitude at specific frequencies, which differed between the two sweeps. This behaviour indicates that the system oscillation has a different equilibrium condition depending on the path followed by the stimuli. Preload and amplitude of the oscillation directly influenced the disc response by changing the nonlinear dynamics and frequency of the jump-phenomenon. These results show that the characterization of the dynamic response of physiological systems should be readdressed to determine potential nonlinearities. Their direct effect on the system function should be further investigated. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of Axial Torsion on Disc Height Distribution: an In Vivo Study

PubMed Central

Espinoza Orías, Alejandro A.; Mammoser, Nicole M.; Triano, John J.; An, Howard S.; Andersson, Gunnar B.J.; Inoue, Nozomu

2016-01-01

Objectives Axial rotation of the torso is commonly used during manipulation treatment of low back pain. Little is known about the effect of these positons on disc morphology. Rotation is a three-dimensional event that is inadequately represented with planar images in the clinic. True quantification of the intervertebral gap can be achieved with a disc height distribution. The objective of this study was to analyze disc height distribution patterns during torsion relevant to manipulation in vivo. Methods Eighty-one volunteers were CT-scanned both in supine and in right 50° rotation positions. Virtual models of each intervertebral gap representing the disc were created with the inferior endplate of each ‘disc’ set as the reference surface and separated into five anatomical zones: four peripheral and one central, corresponding to the footprint of the annulus fibrosus and nucleus pulposus, respectively. Whole-disc and individual anatomical zone disc height distributions were calculated in both positions, and were compared against each other with ANOVA, with significance set at p < 0.05. Results Mean neutral disc height was 7.32 (1.59) mm. With 50° rotation, a small but significant increase to 7.44 (1.52) mm (p < 0.0002) was observed. The right side showed larger separation in most levels, except at L5/S1. The posterior and right zones increased in height upon axial rotation of the spine (p < 0.0001), while the left, anterior and central decreased. Conclusions This study quantified important tensile/compressive changes disc height during torsion. The implications of these mutually opposing changes on spinal manipulation are still unknown. PMID:27059249

Development of a Detailed Volumetric Finite Element Model of the Spine to Simulate Surgical Correction of Spinal Deformities

PubMed Central

Driscoll, Mark; Mac-Thiong, Jean-Marc; Labelle, Hubert; Parent, Stefan

2013-01-01

A large spectrum of medical devices exists; it aims to correct deformities associated with spinal disorders. The development of a detailed volumetric finite element model of the osteoligamentous spine would serve as a valuable tool to assess, compare, and optimize spinal devices. Thus the purpose of the study was to develop and initiate validation of a detailed osteoligamentous finite element model of the spine with simulated correction from spinal instrumentation. A finite element of the spine from T1 to L5 was developed using properties and geometry from the published literature and patient data. Spinal instrumentation, consisting of segmental translation of a scoliotic spine, was emulated. Postoperative patient and relevant published data of intervertebral disc stress, screw/vertebra pullout forces, and spinal profiles was used to evaluate the models validity. Intervertebral disc and vertebral reaction stresses respected published in vivo, ex vivo, and in silico values. Screw/vertebra reaction forces agreed with accepted pullout threshold values. Cobb angle measurements of spinal deformity following simulated surgical instrumentation corroborated with patient data. This computational biomechanical analysis validated a detailed volumetric spine model. Future studies seek to exploit the model to explore the performance of corrective spinal devices. PMID:23991426

Prevalence and Geographic Distribution of Herniated Intervertebral Disc in Korean 19-Year-Old Male from 2008 to 2009: A Study Based on Korean Conscription -National and Geographic Prevalence of Herniated Intervertebral Disc in Korean 19YO Male-

PubMed Central

Lee, Sang Hun; Oh, Chang Hyun; Park, Hyeong-chun; Park, Chong Oon

2013-01-01

Purpose This study was to determine the prevalence of herniated intervertebral disc (HIVD) among Korean 19-year-old male in a large national sample and to compare the prevalence across geographic regions based on the data of conscription. Materials and Methods We analyzed the conscription data of 615508 cases who were 19-year-old male, given an examination for conscription at nationwide Korean Military Manpower Administration from January 2008 to December 2009. Prevalence was determined by dividing the number of cases by the number of persons enrolled for 2 years. The analyses included of a cross-tabulations and nonparametric chi-square to compare the prevalence according to geographic region, disc severity, and conscription year. Results The prevalence of HIVD among 19-year-old male was 0.47%. Seoul had the highest prevalence of HIVD (total HIVD was 0.60%, and severe HIVD was 0.44%). The prevalence of HIVD was lower in Jeollabuk-do and Jeollanam-do (total HIVD was 0.25-0.27%, and severe HIVD was 0.16-0.17%). Annual prevalence of HIVD was slightly decreased in 2009, but geographic distribution annually was not different. Conclusion In Korean 19-year-old male, the national prevalence of adolescent HIVD was 0.60%, but different geographic distribution was observed. It is quite possible that secondary contributing factor(s) interfere with the different geographic prevalence of HIVD. PMID:23918557

Development of gellan gum-based microparticles/hydrogel matrices for application in the intervertebral disc regeneration.

PubMed

Pereira, Diana Ribeiro; Silva-Correia, Joana; Caridade, Sofia Glória; Oliveira, Joao T; Sousa, Rui A; Salgado, Antonio J; Oliveira, Joaquim M; Mano, João F; Sousa, Nuno; Reis, Rui L

2011-10-01

Low back pain is one of the most reported medical conditions associated to intervertebral disc (IVD) degeneration. Nucleus pulposus (NP) is often regarded as the structure where IVD degeneration begins. Gellan gum (GG)-based hydrogels for acellular and cellular tissue engineering strategies have been developed for finding applications as NP substitutes. The innovative strategy is based on the reinforcement of the hydrogel matrix with biocompatible and biodegradable GG microparticles (MPs), which are expected to improve the mechanical properties, while allowing to tailor its degradation rate. In this study, several GG MP/hydrogel disc formulations were prepared by means of mixing high acyl GG (0.75% (w/v)) and low acyl GG (2% (w/v)) GG aqueous solutions at different ratios, namely, 75%:25% (v/v), 50%:50% (v/v), and 25%:75% (v/v), respectively. The GG MP size was measured using a stereo microscope, and their dispersion within the hydrogel matrix was evaluated by means of staining the MPs with Toluidine Blue-O. The developed GG MPs/hydrogel discs were physicochemically characterized by Fourier-transform infrared spectroscopy and (1)H-nuclear magnetic resonance spectroscopy. The swelling behavior and degradation rate were assessed by immersion in a phosphate buffer saline for 14 days. The morphology and mechanical behavior were investigated by scanning electron microscopy and dynamic mechanical analysis, respectively. The mechanical properties of the hydrogel disc were improved by mixing the gels with the MPs. In addition, the possible cytotoxicity of the leachables released by MPs/hydrogel discs was screened in vitro, using a mouse lung fibroblast cell line (L929 cells). To investigate the encapsulation efficacy of L929 cells into the GG MPs/hydrogel discs, cells were stained with DAPI blue/Texas Red-Phalloidin and observed by confocal microscopy, after 24, 48, and 72 h of culturing. A cell viability assay was also performed using Calcein AM staining. The cell culture studies demonstrated that MPs/hydrogel discs are noncytotoxic over L929 cells. It was also demonstrated that L929 cells can be successfully encapsulated into the GG MPs of different formulations, remaining viable after 72 h of culturing. This study showed that GG hydrogel matrices reinforced with cell-loaded MPs could be a candidate strategy for NP regeneration. © Mary Ann Liebert, Inc.

Comparison of radiographic changes after ACDF versus Bryan disc arthroplasty in single and bi-level cases

PubMed Central

Limson, Marc Anthony; Kim, Soo-Bum; Arbatin, Jose Joefrey F.; Chang, Kee-Young; Park, Moon-Soo; Shin, Jae-hyuk; Ju, Yeong-Su

2009-01-01

The object of this study is to compare radiographic outcomes of anterior cervical decompression and fusion (ACDF) versus cervical disc replacement using the Bryan Cervical Disc Prosthesis (Medtronic Sofamor Danek, Memphis, TN) in terms of range of motion (ROM), Functional spinal unit (FSU), overall sagittal alignment (C2–C7), anterior intervertebral height (AIH), posterior intervertebral height (PIH) and radiographic changes at the implanted and adjacent levels. The study consisted of 105 patients. A total of 63 Bryan disc were placed in 51 patients. A single level procedure was performed in 39 patients and a two-level procedure in the other 12. Fifty-four patients underwent ACDF, 26 single level cases and 28 double level cases. The Bryan group had a mean follow-up 19 months (12–38). Mean follow-up for the ACDF group was 20 months (12–40 months). All patients were evaluated using static and dynamic cervical spine radiographs as well as MR imaging. All patients underwent anterior cervical discectomy followed by autogenous bone graft with plate (or implantation of a cage) or the Bryan artificial disc prosthesis. Clinical evaluation included the visual analogue scale (VAS), and neck disability index (NDI). Radiographic evaluation included static and dynamic flexion-extension radiographs using the computer software (Infinitt PiviewSTAR 5051) program. ROM, disc space angle, intervertebral height were measured at the operative site and adjacent levels. FSU and overall sagittal alignment (C2–C7) were also measured pre-operatively, postoperatively and at final follow-up. Radiological change was analyzed using χ2 test (95% confidence interval). Other data were analyzed using the mixed model (SAS enterprises guide 4.1 versions). There was clinical improvement within each group in terms of VAS and NDI scores from pre-op to final follow-up but not significantly between the two groups for both single (VAS p = 0.8371, NDI p = 0.2872) and double (VAS p = 0.2938, NDI p = 0.6753) level surgeries. Overall, ROM and intervertebral height was relatively well maintained during the follow-up in the Bryan group compared to ACDF. Regardless of the number of levels operated on, significant differences were noted for overall ROM of the cervical spine (p < 0.0001) and all other levels except at the upper adjacent level for single level surgeries (p = 0.2872). Statistically significant (p < 0.0001 and p = 0.0172) differences in the trend of intervertebral height measurements between the two groups were noted at all levels except for the AIH of single level surgeries at the upper (p = 0.1264) and lower (p = 0.7598) adjacent levels as well as PIH for double level surgeries at the upper (p = 0.8363) adjacent level. Radiological change was 3.5 times more observed for the ACDF group. Clinical status of both groups, regardless of the number of levels, showed improvement. Although clinical outcomes between the two groups were not significantly different at final follow-up, radiographic parameters, namely ROM and intervertebral heights at the operated site, some adjacent levels as well as FSU and overall sagittal alignment of the cervical spine were relatively well maintained in Bryan group compared to ACDF group. We surmise that to a certain degree, the maintenance of these parameters could contribute to reduce development of adjacent level change. Noteworthy is that radiographic change was 3.5 times more observed for ACDF surgeries. A longer period of evaluation is needed, to see if all these radiographic changes will translate to symptomatic adjacent level disease. PMID:19127374

[Research progress on mechanical performance evaluation of artificial intervertebral disc].

PubMed

Li, Rui; Wang, Song; Liao, Zhenhua; Liu, Weiqiang

2018-03-01

The mechanical properties of artificial intervertebral disc (AID) are related to long-term reliability of prosthesis. There are three testing methods involved in the mechanical performance evaluation of AID based on different tools: the testing method using mechanical simulator, in vitro specimen testing method and finite element analysis method. In this study, the testing standard, testing equipment and materials of AID were firstly introduced. Then, the present status of AID static mechanical properties test (static axial compression, static axial compression-shear), dynamic mechanical properties test (dynamic axial compression, dynamic axial compression-shear), creep and stress relaxation test, device pushout test, core pushout test, subsidence test, etc. were focused on. The experimental techniques using in vitro specimen testing method and testing results of available artificial discs were summarized. The experimental methods and research status of finite element analysis were also summarized. Finally, the research trends of AID mechanical performance evaluation were forecasted. The simulator, load, dynamic cycle, motion mode, specimen and test standard would be important research fields in the future.

Microarray analysis of laser capture microdissected-anulus cells from the human intervertebral disc.

PubMed

Gruber, Helen E; Mougeot, Jean-Luc; Hoelscher, Gretchen; Ingram, Jane A; Hanley, Edward N

2007-05-15

Five Thompson Grade I/II discs (Group 1), 7 Grade III discs (Group 2), and 3 Grade IV discs (Group IV) were studied here in a project approved by the authors' Human Subjects Institutional Review Board. Our objective was to use laser capture microdissection (LCM) to harvest cells from the human anulus and to derive gene expression profiles using microarray analysis. Appropriate gene expression is essential in the intervertebral disc for maintenance of extracellular matrix (ECM), ECM remodeling, and maintenance of a viable disc cell population. During disc degeneration, cell numbers drop, making gene expression studies challenging. LCM was used to harvest cells from paraffin-embedded sections of human anulus tissue. Gene profiling used Affymetrix GeneChip Human X3P arrays. ANOVA and SAM permutation analysis were applied to dCHIP normalized, filtered, and log-transformed gene expression data ( approximately 33,500 probes), and data analyzed to identify genes that were significantly differentially expressed between the 3 groups. We identified 47 genes that were significantly differentially expressed between the 3 groups (P < 0.001 and lowest q values). Compared with the healthiest discs (Grade I/II), 13 genes were up-regulated and 19 down-regulated in both the Grade III and the Grade IV discs. Genes with biologic significance regulated during degeneration involved cell senescence, low cell division rates, hypoxia-related genes, heat-shock protein 70 interacting protein, neuropilin 2, and interleukin-23p19 (interleukin-12 family). Results expand our understanding of disc aging and degeneration and show that LCM is a valuable technique that can be used to collect mRNA amounts adequate for microarray analysis from the sparse cell population of the human anulus.

Effects of Axial Torsion on Disc Height Distribution: An In Vivo Study.

PubMed

Espinoza Orías, Alejandro A; Mammoser, Nicole M; Triano, John J; An, Howard S; Andersson, Gunnar B J; Inoue, Nozomu

2016-05-01

Axial rotation of the torso is commonly used during manipulation treatment of low back pain. Little is known about the effect of these positions on disc morphology. Rotation is a three-dimensional event that is inadequately represented with planar images in the clinic. True quantification of the intervertebral gap can be achieved with a disc height distribution. The objective of this study was to analyze disc height distribution patterns during torsion relevant to manipulation in vivo. Eighty-one volunteers were computed tomography-scanned both in supine and in right 50° rotation positions. Virtual models of each intervertebral gap representing the disc were created with the inferior endplate of each "disc" set as the reference surface and separated into 5 anatomical zones: 4 peripheral and 1 central, corresponding to the footprint of the annulus fibrosus and nucleus pulposus, respectively. Whole-disc and individual anatomical zone disc height distributions were calculated in both positions and were compared against each other with analysis of variance, with significance set at P < .05. Mean neutral disc height was 7.32 mm (1.59 mm). With 50° rotation, a small but significant increase to 7.44 mm (1.52 mm) (P < .0002) was observed. The right side showed larger separation in most levels, except at L5/S1. The posterior and right zones increased in height upon axial rotation of the spine (P < .0001), whereas the left, anterior, and central decreased. This study quantified important tensile/compressive changes disc height during torsion. The implications of these mutually opposing changes on spinal manipulation are still unknown. Copyright © 2016 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

[Treatment of postoperative nonunion of fracture of lower limb with bone grafting by intervertebral disc endoscope].

PubMed

Zhang, Jianlin; Tan, Yu'e; Ye, Jun; Han, Fangmin

2012-02-01

To explore the effectiveness of bone grafting by intervertebral disc endoscope for postoperative nonunion of fracture of lower limb. Between August 2004 and August 2008, 40 patients (23 males and 17 females) with postoperative nonunion of femoral and tibial fracture, aged 20-63 years (mean, 41.5 years) were treated. Nonunion of fracture occurred at 10-16 months after internal fixation. During the first operation, the internal fixation included interlocking intramedullary nailing of femoral fracture in 12 cases and plate in 16 cases, and interlocking intramedullary nailing of tibial fractures in 9 cases and plate in 3 cases. The X-ray films showed hypertrophic nonunion in 24 cases, common nonunion in 3 cases, and atrophic nonunion in 13 cases. The average operation time was 61 minutes (range, 40-80 minutes), and the blood loss was 80-130 mL (mean, 100 mL). The hospitalization time were 6-11 days (mean, 8.1 days). Incisions healed by first intention in all patients with no complication of infection or neurovascular injury. Forty patients were followed up 10-16 months (mean, 12.3 months). The X-ray films showed that all patients achieved healing of fracture after 4-10 months (mean, 6.8 months). No pain, disfunction, or internal fixation failure occurred. Bone grafting by intervertebral disc endoscope is an effective method for treating postoperative nonunion of femoral and tibial fracture.

A selective inhibition of c-Fos/activator protein-1 as a potential therapeutic target for intervertebral disc degeneration and associated pain.

PubMed

Makino, Hiroto; Seki, Shoji; Yahara, Yasuhito; Shiozawa, Shunichi; Aikawa, Yukihiko; Motomura, Hiraku; Nogami, Makiko; Watanabe, Kenta; Sainoh, Takeshi; Ito, Hisakatsu; Tsumaki, Noriyuki; Kawaguchi, Yoshiharu; Yamazaki, Mitsuaki; Kimura, Tomoatsu

2017-12-05

Intervertebral disc (IVD) degeneration is a major cause of low back pain. The transcription factor c-Fos/Activator Protein-1 (AP-1) controls the expression of inflammatory cytokines and matrix metalloproteinases (MMPs) that contribute to the pathogenesis IVD degeneration. We investigated the effects of inhibition of c-Fos/AP-1 on IVD degeneration and associated pain. A selective inhibitor, T-5224, significantly suppressed the interleukin-1β-induced up-regulation of Mmp-3, Mmp-13 and Adamts-5 transcription in human nucleus pulposus cells and in a mouse explant culture model of IVD degeneration. We used a tail disc percutaneous needle puncture method to further assess the effects of oral administration of T-5224 on IVD degeneration. Analysis of disc height, T2-magnetic resonance imaging (MRI) findings, and histology revealed that IVD degeneration was significantly mitigated by T-5224. Further, oral administration of T-5224 ameliorated pain as indicated by the extended tail-flick latency in response to heat stimulation of rats with needle-puncture-induced IVD degeneration. These findings suggest that the inhibition of c-Fos/AP-1 prevents disc degeneration and its associated pain and that T-5224 may serve as a drug for the prevention of IVD degeneration.

Hyaluronic Acid (HA)-Polyethylene glycol (PEG) as injectable hydrogel for intervertebral disc degeneration patients therapy

NASA Astrophysics Data System (ADS)

Putri Kwarta, Cityta; Widiyanti, Prihartini; Siswanto

2017-05-01

Chronic Low Back Pain (CLBP) is one health problem that is often encountered in a community. Inject-able hydrogels are the newest way to restore the disc thickness and hydration caused by disc degeneration by means of minimally invasive surgery. Thus, polymers can be combined to improve the characteristic properties of inject-able hydrogels, leading to use of Hyaluronic Acid (a natural polymer) and Polyethylene glycol (PEG) with Horse Radish Peroxide (HRP) cross linker enzymes. The swelling test results, which approaches were the ideal disc values, were sampled with variation of enzyme concentrations of 0.25 µmol/min/mL. The enzyme concentrations were 33.95%. The degradation test proved that the sample degradation increased along with the decrease of the HRP enzyme concentration. The results of the cytotoxicity assay with MTT assay method showed that all samples resulted in the 90% of living cells are not toxic. In vitro injection, models demonstrated that higher concentration of the enzymes was less state of gel which would rupture when released from the agarose gel. The functional group characterization shows the cross linking bonding in sample with enzyme adding. The conclusion of this study is PEG-HA-HRP enzyme are safe polymer composites which have a potential to be applied as an injectable hydrogel for intervertebral disc degeneration.

Prediction of glycosaminoglycan synthesis in intervertebral disc under mechanical loading.

PubMed

Gao, Xin; Zhu, Qiaoqiao; Gu, Weiyong

2016-09-06

The loss of glycosaminoglycan (GAG) content is a major biochemical change during intervertebral disc (IVD) degeneration. Abnormal mechanical loading is one of the major factors causing disc degeneration. In this study, a multiscale mathematical model was developed to quantify the effect of mechanical loading on GAG synthesis. This model was based on a recently developed cell volume dependent GAG synthesis theory that predicts the variation of GAG synthesis rate of a cell under the influence of mechanical stimuli, and the biphasic theory that describes the deformation of IVD under mechanical loading. The GAG synthesis (at the cell level) was coupled with the mechanical loading (at the tissue level) via a cell-matrix unit approach which established a relationship between the variation of cell dilatation and the local tissue dilatation. This multiscale mathematical model was used to predict the effect of static load (creep load) on GAG synthesis in bovine tail discs. The predicted results are in the range of experimental results. This model was also used to investigate the effect of static (0.2MPa) and diurnal loads (0.1/0.3MPa and 0.15/0.25MPa in 12/12 hours shift with an average of 0.2MPa over a cycle) on GAG synthesis. It was found that static load and diurnal loads have different effects on GAG synthesis in a diurnal cycle, and the diurnal load effects depend on the amplitude of the load. The model is important to understand the effect of mechanical loading at the tissue level on GAG synthesis at the cellular level, as well as to optimize the mechanical loading in growing engineered tissue. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ablation of intervertebral discs in dogs using a MicroJet-assisted dye-enhanced injection device coupled with the diode laser

NASA Astrophysics Data System (ADS)

Bartels, Kenneth E.; Henry, George A.; Dickey, D. Thomas; Stair, Ernest L.; Powell, Ronald; Schafer, Steven A.; Nordquist, Robert E.; Frederickson, Christopher J.; Hayes, Donald J.; Wallace, David B.

1998-07-01

Use of holmium laser energy for vaporization/coagulation of the nucleus pulposus in canine intervertebral discs has been previously reported and is currently being applied clinically in veterinary medicine. The procedure was originally developed in the canine model and intended for potential human use. Since the pulsed (15 Hz) holmium laser energy exerts photomechanical and photothermal effects, the potential for extrusion of additional disc material to the detriment of the patient is possible using the procedure developed for the dog. To reduce this potential complication, use of diode laser (805 nm - CW mode) energy, coupled with indocyanine green (ICG) as a selective laser energy absorber, was formulated as a possible alternative. Delivery of the ICG and diode laser energy was through a MicroJet device that could dispense dye interactively between individual laser 'shots.' Results have shown that it is possible to selectively ablate nucleus pulposus in the canine model using the device described. Acute observations (gross and histopathologic) illustrate that accurate placement of the spinal needle before introduction of the MicroJet device is critically dependent on the expertise of the interventional radiologist. In addition, the success of the overall technique depends on consistent delivery of both ICG and diode laser energy. Minimizing tissue carbonization on the tip of the MicroJet device is also of crucial importance for effective application of the technique in clinical veterinary medicine.

38 CFR 4.66 - Sacroiliac joint.

Code of Federal Regulations, 2013 CFR

2013-07-01

... accompanied by limitation of flexion and extension of the hip. Traumatism is a rare cause of disability in... paralysis attributable to disease affecting the lumbar vertebrae and the intervertebral disc. ...

38 CFR 4.66 - Sacroiliac joint.

Code of Federal Regulations, 2014 CFR

2014-07-01

... accompanied by limitation of flexion and extension of the hip. Traumatism is a rare cause of disability in... paralysis attributable to disease affecting the lumbar vertebrae and the intervertebral disc. ...

38 CFR 4.66 - Sacroiliac joint.

Code of Federal Regulations, 2012 CFR

2012-07-01

... accompanied by limitation of flexion and extension of the hip. Traumatism is a rare cause of disability in... paralysis attributable to disease affecting the lumbar vertebrae and the intervertebral disc. ...

38 CFR 4.66 - Sacroiliac joint.

Code of Federal Regulations, 2010 CFR

2010-07-01

... accompanied by limitation of flexion and extension of the hip. Traumatism is a rare cause of disability in... paralysis attributable to disease affecting the lumbar vertebrae and the intervertebral disc. ...

38 CFR 4.66 - Sacroiliac joint.

Code of Federal Regulations, 2011 CFR

2011-07-01

... accompanied by limitation of flexion and extension of the hip. Traumatism is a rare cause of disability in... paralysis attributable to disease affecting the lumbar vertebrae and the intervertebral disc. ...

Effects of Tobacco Smoking on the Degeneration of the Intervertebral Disc: A Finite Element Study

PubMed Central

Elmasry, Shady; Asfour, Shihab; de Rivero Vaccari, Juan Pablo; Travascio, Francesco

2015-01-01

Tobacco smoking is associated with numerous pathological conditions. Compelling experimental evidence associates smoking to the degeneration of the intervertebral disc (IVD). In particular, it has been shown that nicotine down-regulates both the proliferation rate and glycosaminoglycan (GAG) biosynthesis of disc cells. Moreover, tobacco smoking causes the constriction of the vascular network surrounding the IVD, thus reducing the exchange of nutrients and anabolic agents from the blood vessels to the disc. It has been hypothesized that both nicotine presence in the IVD and the reduced solute exchange are responsible for the degeneration of the disc due to tobacco smoking, but their effects on tissue homeostasis have never been quantified. In this study, a previously presented computational model describing the homeostasis of the IVD was deployed to investigate the effects of impaired solute supply and nicotine-mediated down-regulation of cell proliferation and biosynthetic activity on the health of the disc. We found that the nicotine-mediated down-regulation of cell anabolism mostly affected the GAG concentration at the cartilage endplate, reducing it up to 65% of the value attained in normal physiological conditions. In contrast, the reduction of solutes exchange between blood vessels and disc tissue mostly affected the nucleus pulposus, whose cell density and GAG levels were reduced up to 50% of their normal physiological levels. The effectiveness of quitting smoking on the regeneration of a degenerated IVD was also investigated, and showed to have limited benefit on the health of the disc. A cell-based therapy in conjunction with smoke cessation provided significant improvements in disc health, suggesting that, besides quitting smoking, additional treatments should be implemented in the attempt to recover the health of an IVD degenerated by tobacco smoking. PMID:26301590

Imaging of Herniated Discs of the Cervical Spine: Inter-Modality Differences between 64-Slice Multidetector CT and 1.5-T MRI

PubMed Central

Yi, Ji Sook; Han, Jong Kyu; Kim, Hyun-Joo

2015-01-01

Objective To assess inter-modality variability when evaluating cervical intervertebral disc herniation using 64-slice multidetector-row computed tomography (MDCT) and magnetic resonance imaging (MRI). Materials and Methods Three musculoskeletal radiologists independently reviewed cervical spine 1.5-T MRI and 64-slice MDCT data on C2-3 though C6-7 of 51 patients in the context of intervertebral disc herniation. Interobserver and inter-modality agreements were expressed as unweighted kappa values. Weighted kappa statistics were used to assess the extents of agreement in terms of the number of involved segments (NIS) in disc herniation and epicenter measurements collected using MDCT and MRI. Results The interobserver agreement rates upon evaluation of disc morphology by the three radiologists were in fair to moderate agreement (k = 0.39-0.53 for MDCT images; k = 0.45-0.56 for MRIs). When the disc morphology was categorized into two and four grades, the inter-modality agreement rates were moderate (k-value, 0.59) and substantial (k-value, 0.66), respectively. The inter-modality agreements for evaluations of the NIS (k-value, 0.78) and the epicenter (k-value, 0.79) were substantial. Also, the interobserver agreements for the NIS (CT; k-value, 0.85 and MRI; k-value, 0.88) and epicenter (CT; k-value, 0.74 and MRI; k-value, 0.70) evaluations by two readers were substantial. MDCT tended to underestimate the extent of herniated disc lesions compared with MRI. Conclusion Multidetector-row computed tomography and MRI showed a moderate-to-substantial degree of inter-modality agreement for the assessment of herniated cervical discs. MDCT images have a tendency to underestimate the anterior/posterior extent of the herniated disc compared with MRI. PMID:26175589

How Long and Low Can You Go? Effect of Conformation on the Risk of Thoracolumbar Intervertebral Disc Extrusion in Domestic Dogs

PubMed Central

Packer, Rowena M. A.; Hendricks, Anke; Volk, Holger A.; Shihab, Nadia K.; Burn, Charlotte C.

2013-01-01

Intervertebral disc extrusion (IVDE) is a common neurological disorder in certain dog breeds, resulting in spinal cord compression and injury that can cause pain and neurological deficits. Most disc extrusions are reported in chondrodystrophic breeds (e.g. Dachshunds, Basset Hounds, Pekingese), where selection for ‘long and low’ morphologies is linked with intervertebral discs abnormalities that predispose dogs to IVDE. The aim of this study was to quantify the relationship between relative thoracolumbar vertebral column length and IVDE risk in diverse breeds. A 14 month cross-sectional study of dogs entering a UK small animal referral hospital for diverse disorders including IVDE was carried out. Dogs were measured on breed-defining morphometrics, including back length (BL) and height at the withers (HW). Of 700 dogs recruited from this referral population, measured and clinically examined, 79 were diagnosed with thoracolumbar IVDE following diagnostic imaging ± surgery. The BL:HW ratio was positively associated with IVDE risk, indicating that relatively longer dogs were at increased risk, e.g. the probability of IVDE was 0.30 for Miniature Dachshunds when BL:HW ratio equalled 1.1, compared to 0.68 when BL:HW ratio equalled 1.5. Additionally, both being overweight and skeletally smaller significantly increased IVDE risk. Therefore, selection for longer backs and miniaturisation should be discouraged in high-risk breeds to reduce IVDE risk. In higher risk individuals, maintaining a lean body shape is particularly important to reduce the risk of IVDE. Results are reported as probabilities to aid decision-making regarding breed standards and screening programmes reflecting the degree of risk acceptable to stakeholders. PMID:23894518

How long and low can you go? Effect of conformation on the risk of thoracolumbar intervertebral disc extrusion in domestic dogs.

PubMed

Packer, Rowena M A; Hendricks, Anke; Volk, Holger A; Shihab, Nadia K; Burn, Charlotte C

2013-01-01

Intervertebral disc extrusion (IVDE) is a common neurological disorder in certain dog breeds, resulting in spinal cord compression and injury that can cause pain and neurological deficits. Most disc extrusions are reported in chondrodystrophic breeds (e.g. Dachshunds, Basset Hounds, Pekingese), where selection for 'long and low' morphologies is linked with intervertebral discs abnormalities that predispose dogs to IVDE. The aim of this study was to quantify the relationship between relative thoracolumbar vertebral column length and IVDE risk in diverse breeds. A 14 month cross-sectional study of dogs entering a UK small animal referral hospital for diverse disorders including IVDE was carried out. Dogs were measured on breed-defining morphometrics, including back length (BL) and height at the withers (HW). Of 700 dogs recruited from this referral population, measured and clinically examined, 79 were diagnosed with thoracolumbar IVDE following diagnostic imaging ± surgery. The BL:HW ratio was positively associated with IVDE risk, indicating that relatively longer dogs were at increased risk, e.g. the probability of IVDE was 0.30 for Miniature Dachshunds when BL:HW ratio equalled 1.1, compared to 0.68 when BL:HW ratio equalled 1.5. Additionally, both being overweight and skeletally smaller significantly increased IVDE risk. Therefore, selection for longer backs and miniaturisation should be discouraged in high-risk breeds to reduce IVDE risk. In higher risk individuals, maintaining a lean body shape is particularly important to reduce the risk of IVDE. Results are reported as probabilities to aid decision-making regarding breed standards and screening programmes reflecting the degree of risk acceptable to stakeholders.

The effect of the X-Stop implantation on intervertebral foramen, segmental spinal canal length and disc space in elderly patients with lumbar spinal stenosis.

PubMed

Wan, Zongmiao; Wang, Shaobai; Kozanek, Michal; Xia, Qun; Mansfield, Frederick L; Lü, Guohua; Wood, Kirkham B; Li, Guoan

2012-03-01

To evaluate the biomechanical effect of the X-Stop device on the intervertebral foramen (IVF) and segmental spinal canal length (SSCL), as well as the intervertebral disc space at the implanted and the adjacent segments in patients with lumbar spinal stenosis (LSS). Eight elderly patients with LSS, scheduled for X-stop implantation, were CT or MRI scanned to construct 3D vertebral models (L2-S1). Before and after the surgery, each patient was also imaged using a dual-fluoroscopic image system during weight-bearing standing and maximum extension-flexion. The positions of the vertebrae were then determined using an established 2D-3D model matching method. The data revealed that the postoperative IVF area was significantly increased by 32.9% (or 32 mm2) (p<0.05) and the IVF width was increased by 24.4% (or 1.1 mm, p=0.06) during extension, but with minimal change in standing and flexion. The IVF heights were significantly (p<0.05) increased at standing by 1.2 mm and extension by 1.8 mm, but not at flexion. The SSCL were significantly (p<0.05) increased at extension by 1.2 mm, but not at standing and flexion. Anterior disc space of the implanted level was significantly decreased from 8.0 to 6.6 mm during standing. The X-Stop implantation efficiently enlarged the IVF area in the elderly patients with LSS at the operated level with little biomechanical effect immediately on the superior and inferior adjacent levels. However, it reduced the anterior disc space at the implanted level.

Anatomy of the Spine

MedlinePlus

... is called the conus medullaris. There is a thread that continues from the conus called the filum ... bodies, the facet joint created by their articular processes, the intervertebral disc between them and the associated ...

Lactoferricin Enhances BMP7-Stimulated Anabolic Pathways in Intervertebral Disc Cells

PubMed Central

Ellman, Michael B; Kim, Jaesung; An, Howard S; Chen, Di; Kc, Ranjan; Li, Xin; Xiao, Guozhi; Yan, Dongyao; Suh, Joon; van Wijnen, Andre J.; Wang, James H-C; Kim, Su-Gwan; Im, Hee-Jeong

2013-01-01

Bone-morphogenetic protein-7 (BMP7) is a well-known anabolic and anti-catabolic growth factor on intervertebral (IVD) matrix and cell homeostasis. Similarly, lactoferricin B (LfcinB) has recently been shown to have pro-anabolic, anti-catabolic, anti-oxidative and/or anti-inflammatory effects in bovine disc cells in vitro. In this study, we investigated the potential benefits of using combined peptide therapy with LfcinB and BMP7 for intervertebral disc (IVD) matrix repair and to understand cellular and signaling mechanisms controlled by these factors. We studied the effects of BMP7 and LfcinB as individual treatments and combined therapy on bovine nucleus pulposus (NP) cells by assessing proteoglycan (PG) accumulation and synthesis, and the expression of matrix protein aggrecan and transcription factor SOX-9. We also analyzed the role of noggin, a BMP antagonist, in IVD tissue and examined its effect after stimulation with LfcinB. To understand the molecular mechanisms by which LfcinB synergizes with BMP7, we investigated the ERK-SP1 axis as a downstream intracellular signaling regulator involved in BMP7 and LfcinB-mediated activities. Treatment of bovine NP cells cultured in alginate with LfcinB plus BMP7 synergistically stimulates PG synthesis and accumulation in part by upregulation of aggrecan gene expression. The synergism results from LfcinB-mediated activation of Sp1 and SMAD signaling pathways by (i) phosphorylation of SMAD 1/5/8; (ii) downregulation of SMAD inhibitory factors [i.e., noggin (BMP receptor antagonist) and SMAD6 (inhibitory SMAD)]; and (iii) upregulation of SMAD4 (universal co-SMAD). These data indicate that LfcinB-suppression of noggin may eliminate the negative feedback of BMP7, thereby maximizing biological activity of BMP7 and ultimately shifting homeostasis to a pro-anabolic state in disc cells. We propose that combination growth factor therapy using BMP7 and LfcinB may be beneficial for treatment of disc degeneration. PMID:23644135

[Effect of electroacupuncture intervention on expression of extracellular matrix collagen and metabolic enzymes].

PubMed

Liao, Jun; Zhang, Le; Ke, Mei-gui; Xu, Teng

2013-12-01

To observe the effect of electroacupuncture (EA) at "Dazhui" (GV 14) on the contents of extracellular matrix (ECM), collagen type II (COL-II), collagen type V (COL-V), matrix metalloproteinase (MMP)-13, tissue inhibitor of metalloproteinase (TIMP)-1 in rats with cervicovertebral disc degeneration so as to explore its mechanism underlying relief of intervertebral disc degeneration. A total of 28 SD rats were randomly divided into sham group (n = 7), model group (n = 7), EA group (n = 7) and medication group (n = 7). The model of cervical intervertebral disc degeneration was established by trans-section of the deep neck splenius, the longest muscles of head, neck costocervicalis, head semi-spinatus muscle, supraspinous ligament and interspinal ligaments of cervical 2-7 segments, etc. to produce imbalance between the dynamic and static force. EA was applied to "Dazhui" (GV 14) for 30 min, once daily for 28 days, with a 2 days' interval between two courses. Animals of the medication group were treated by oral administration of meloxicam tablets (0.75 mg/kg) once daily for 28 days, with a 2 days' interval between two courses. Immunohistochemistry was used to measure the expression of ECM, COL- II, COL-V, MMP-13 and TIMP-1 in the cervicovertebral disc tissue. Compared with the sham group, the expression levels of ECM and COL-II proteins in the cervicovertebral disc tissue were significantly decreased in the model group (P < 0.01), while COL-V and MMP-13 expression levels in the model group were significantly increased (P < 0.01, P < 0.05). Compared with the model group, both ECM and COL-Il expression levels were considerably increased in the EA group and medication group (P < 0.01), while COL-V and MMP-13 expression levels were considerably down-regulated (P < 0.01, P < 0.05). No significant differences were found among the four groups in TIMP-1 expression levels (P > 0.05). EA of "Dazhui" (GV 14) can effectively regulate extracellular matrix system in rats with cervical intervertebral disc degeneration, which is possibly related to its effect in relieving cervical spondylosis.

[LOCATION CHANGE OF ROTATION CENTER AFTER SINGLE SEGMENTAL CERVICAL DISC REPLACEMENT WITH ProDisc-C].

PubMed

Lou, Jigang; Liu, Hao; Rong, Xin; Gong, Quan; Song, Yueming; Li, Tao

2015-01-01

To evaluate the effectiveness of the single segmental cervical disc replacement with ProDisc-C, and to explore the location change of the flexion/extension center of rotation (COR) of the target level as well as its clinical significance. Between June 2010 and February 2012, 23 patients underwent single segmental cervical disc replacement with ProDisc-C, and the clinical data were retrospectively analyzed. Of 23 patients, 9 were male, and 14 were female with the age range from 27 to 65 years (mean, 45 years), and the disease duration ranged from 10 to 84 months (mean, 25 months). There were 15 patients with radiculopathy, 5 patients with myelopathy, and 3 patients with mixed cervical spondylosis. The involved segments were C4,5 in 5 cases, C5,6 in 14 cases, and C6,7 in 4 cases. Japanese Orthopaedic Association (JOA) score and neck disability index (NDI) were adopted to evaluate the effectiveness. Preoperative and Postoperative radiographic parameters, such as cervical overall range of motion (ROM), target segmental ROM, the adjacent segmental ROM, and intervertebral height were compared. Besides, the location changes of the COR of the target level were further analyzed by the alteration of its coordinates (COR-X, COR-Y), and the relationships between the location changes of the COR and the effectiveness or the radiographic results were analyzed. All the operations were completed successfully; 1 case had hoarseness after operation, which disappeared at 3 months after operation. All cases were followed up 18.3 months on average (range, 6-36 months). There was no device migration, loosening, subsidence, or fracture at last follow-up. The JOA score increased significantly and the NDI score decreased significantly at last follow-up when compared with preoperative scores (P < 0.05). No difference was found in the cervical overall ROM, target segmental ROM, the adjacent segmental ROM, and the COR-Y of the target level between pre-operation and last follow-up (P > 0.05); while the intervertebral height and the COR-X increased significantly (P < 0.05). The change of the COR-X had no obvious correlation with the postoperative JOA, NDI, and target segmental ROM (P > 0.05). According to whether the difference of the COR-X between pre- and post-operation was less than the average value 1.86 mm or not, the patients were divided into 2 groups; significant difference was shown in the postoperative target segmental ROM between 2 groups (P < 0.05), but no significant difference was found in the postoperative JOA, NDI, cervical overall ROM, adjacent segmental ROM, and the intervertebral height between 2 groups (P > 0.05). Single segmental cervical disc replacement with ProDisc-C can obtain satisfactory outcomes. The cervical overall ROM, target segmental ROM, and adjacent segmental ROM can be effectively maintained, and the intervertebral height is increased. The location of the flexion/extension COR of the target segment shifts forward after insertion of the ProDisc-C prosthesis, and the postoperative target segmental ROM becomes smaller as the distance of the displacement of the COR becomes greater.

Towards an affordable deep learning system: automated intervertebral disc detection in x-ray images

NASA Astrophysics Data System (ADS)

Sa, Ruhan; Owens, William; Wiegand, Raymond; Chaudhary, Vipin

2017-03-01

Adult Spinal Deformity is a prominent medical issue with about 68% of the elderly population suffering from the disease.1 Detailed biomechanical assessment is needed both in the presurgical planning of structural spinal deformity as well as in early functional biomechanical compensation in ambulatory spinal pain patients. When considering automation of this process, we have to look at photographic intervertebral disc detection technique as a way to produce a detailed model of the spine with appropriate measurements required to make efficient and accurate decisions on patient care. Deep convolutional neural network (CNN) has given remarkable results in object recognition tasks in recent years. However, massive training data, computational resources and long training time is needed for both training a deep network from scratch or finetuning a network. Using pretrained model as feature extractor has shown promising result for moderate sized medical data.2 However, most work have extracted features from the last layer and little has been explored in terms of the number of convolutional layers needed for best performance. In this work we trained Support Vector Machine (SVM) classifiers on different layers of CaffeNet3 features to show that deeper the better concept does not hold for task such as intervertebral disc detection. Furthermore, our experimental results show the potential of using very small training data, such as 15 annotated medical images in our experiment, to yield satisfactory classification performance with accuracy up to 97.2%.

Retroperitoneal oblique corridor to the L2-S1 intervertebral discs in the lateral position: an anatomic study.

PubMed

Davis, Timothy T; Hynes, Richard A; Fung, Daniel A; Spann, Scott W; MacMillan, Michael; Kwon, Brian; Liu, John; Acosta, Frank; Drochner, Thomas E

2014-11-01

Access to the intervertebral discs from L2-S1 in one surgical position can be challenging. The transpsoas minimally invasive surgical (MIS) approach is preferred by many surgeons, but this approach poses potential risk to neural structures of the lumbar plexus as they course through the psoas. The lumbar plexus and iliac crest often restrict the L4-5 disc access, and the L5-S1 level has not been a viable option from a direct lateral approach. The purpose of the present study was to investigate an MIS oblique corridor to the L2-S1 intervertebral disc space in cadaveric specimens while keeping the specimens in a lateral decubitus position with minimal disruption of the psoas and lumbar plexus. Twenty fresh-frozen full-torso cadaveric specimens were dissected, and an oblique anatomical corridor to access the L2-S1 discs was examined. Measurements were taken in a static state and with mild retraction of the psoas. The access corridor was defined at L2-5 as the left lateral border of the aorta (or iliac artery) and the anterior medial border of the psoas. The L5-S1 corridor of access was defined transversely from the midsagittal line of the inferior endplate of L-5 to the medial border of the left common iliac vessel and vertically to the first vascular structure that crosses midline. The mean access corridor diameters in the static state and with mild psoas retraction, respectively, were as follows: at L2-3, 18.60 mm and 25.50 mm; at L3-4, 19.25 mm and 27.05 mm; and at L4-5, 15.00 mm and 24.45 mm. The L5-S1 corridor mean values were 14.75 mm transversely, from midline to the left common iliac vessel and 23.85 mm from the inferior endplate of L-5 cephalad to the first midline vessel. The oblique corridor allows access to the L2-S1 discs while keeping the patient in a lateral decubitus position without a break in the table. Minimal psoas retraction without significant tendon disruption allowed for a generous corridor to the disc space. The L5-S1 disc space can be accessed from an oblique angle consistently with gentle retraction of the iliac vessels. This study supports the potential of an MIS oblique retroperitoneal approach to the L2-S1 discs.

Collagen turnover in normal and degenerate human intervertebral discs as determined by the racemization of aspartic acid.

PubMed

Sivan, Sarit-Sara; Wachtel, Ellen; Tsitron, Eve; Sakkee, Nico; van der Ham, Frits; Degroot, Jeroen; Roberts, Sally; Maroudas, Alice

2008-04-04

Knowledge of rates of protein turnover is important for a quantitative understanding of tissue synthesis and catabolism. In this work, we have used the racemization of aspartic acid as a marker for the turnover of collagen obtained from healthy and pathological human intervertebral disc matrices. We measured the ratio of the d- and l-isomers in collagen extracted from these tissues as a function of age between 16 and 77 years. For collagen taken from healthy discs, the fractional increase of d-Asp was found to be 6.74 x 10(-4)/year; for degenerate discs, the corresponding rate was 5.18 x 10(-4)/year. Using the racemization rate found previously for the stable population of collagen molecules in dentin, we found that the rate of collagen turnover (k(T)) in discs is not constant but rather a decreasing function of age. The average turnover rate in normal disc between the ages of 20 and 40 is 0.00728 +/- 0.00275/year, and that between the ages of 50 and 80 is 0.00323 +/- 0.000947/year, which correspond to average half-lives of 95 and 215 years, respectively. Turnover of collagen from degenerate discs may be more rapid than that found for normal discs; however, statistical analysis leaves this point uncertain. The finding of a similar correlation between the accumulation of d-Asp and that of pentosidine for three normal collagenous tissues further supports the idea that the accumulation of pentosidine in a particular tissue can, along with the racemization of aspartic acid, be used as a reliable measure of protein turnover.

METABOLIC EFFECTS OF ANGULATION, COMPRESSION AND REDUCED MOBILITY ON ANNULUS FIBROSIS IN A MODEL OF ALTERED MECHANICAL ENVIRONMENT IN SCOLIOSIS

PubMed Central

Stokes, Ian A.F.; McBride, Carole; Aronsson, David D.; Roughley, Peter J.

2013-01-01

Study Design Comparison of disc tissue from rat tails in six groups having different mechanical conditions imposed. Objectives To identify disc annulus changes associated with the supposed altered biomechanical environment in a spine with scoliosis deformity using an immature rat model that produces disc narrowing and wedging. Background Intervertebral discs become wedged and narrowed in a scoliosis curve, probably due in part to altered biomechanical environment. Methods Tail discs of 5-week-old immature Sprague-Dawley rats were subjected to an altered mechanical environment using an external apparatus applying permutations of loading and deformity for 5 weeks. Four groups of rats (A) 15 degrees Angulation, (B) Angulation with 0.1 MPa Compression, (C) 0.1 MPa Compression, and (R) Reduced mobility, together with a sham and a control group were studied. Disc height changes and matrix composition (water, DNA, GAG and HA content) were measured after 5 weeks, and proline and sulphate incorporation and mRNA expression were measured at 5 days and 5 weeks. Results After 5 weeks, disc space was significantly narrowed relative to internal controls in all four intervention groups. Water content and cellularity (DNA content) were not different at interventional levels relative to internal controls and not different between the concave and convex sides of the angulated discs. There was increased GAG content in compressed tissue (in Groups B and C), as expected, and compression resulted in a decrease in hyaluronic acid size. Slightly increased incorporation of tritiated-proline into the concave side of angulated discs and compressed discs was observed. Asymmetries of gene expression in Groups A and B, and some group-wise differences, did not identify consistent patterns associating the discs’ responses to mechanical alterations. Conclusions Intervertebral discs in this model underwent substantial narrowing after 5 weeks, with minimal alteration in tissue composition and minimal evidence of metabolic changes. PMID:27927288

Genetics Home Reference: intervertebral disc disease

MedlinePlus

... periodic or chronic pain in the back or neck. Pain is often worse when sitting, bending, twisting, or ... Version: Low Back Pain Merck Manual Consumer Version: Neck Pain Patient Support and Advocacy Resources (3 links) American ...

An experimental and finite element poroelastic creep response analysis of an intervertebral hydrogel disc model in axial compression.

PubMed

Silva, P; Crozier, S; Veidt, M; Pearcy, M J

2005-07-01

A hydrogel intervertebral disc (IVD) model consisting of an inner nucleus core and an outer anulus ring was manufactured from 30 and 35% by weight Poly(vinyl alcohol) hydrogel (PVA-H) concentrations and subjected to axial compression in between saturated porous endplates at 200 N for 11 h, 30 min. Repeat experiments (n=4) on different samples (N=2) show good reproducibility of fluid loss and axial deformation. An axisymmetric nonlinear poroelastic finite element model with variable permeability was developed using commercial finite element software to compare axial deformation and predicted fluid loss with experimental data. The FE predictions indicate differential fluid loss similar to that of biological IVDs, with the nucleus losing more water than the anulus, and there is overall good agreement between experimental and finite element predicted fluid loss. The stress distribution pattern indicates important similarities with the biological IVD that includes stress transference from the nucleus to the anulus upon sustained loading and renders it suitable as a model that can be used in future studies to better understand the role of fluid and stress in biological IVDs.

Glucosamine Supplementation Demonstrates a Negative Effect On Intervertebral Disc Matrix in an Animal Model of Disc Degeneration

PubMed Central

Jacobs, Lloydine; Vo, Nam; Coehlo, J. Paulo; Dong, Qing; Bechara, Bernard; Woods, Barrett; Hempen, Eric; Hartman, Robert; Preuss, Harry; Balk, Judith; Kang, James; Sowa, Gwendolyn

2013-01-01

Study Design Laboratory based controlled in vivo study Objective To determine the in vivo effects of oral glucosamine sulfate on intervertebral disc degeneration Summary of Background Data Although glucosamine has demonstrated beneficial effect in articular cartilage, clinical benefit is uncertain. A CDC report from 2009 reported that many patients are using glucosamine supplementation for low back pain (LBP), without significant evidence to support its use. Because disc degeneration is a major contributor of LBP, we explored the effects of glucosamine on disc matrix homeostasis in an animal model of disc degeneration. Methods Eighteen skeletally mature New Zealand White rabbits were divided into four groups: control, annular puncture, glucosamine, and annular puncture+glucosamine. Glucosamine treated rabbits received daily oral supplementation with 107mg/day (weight based equivalent to human 1500mg/day). Annular puncture surgery involved puncturing the annulus fibrosus (AF) of 3 lumbar discs with a 16G needle to induce degeneration. Serial MRIs were obtained at 0, 4, 8, 12, and 20 weeks. Discs were harvested at 20 weeks for determination of glycosaminoglycan(GAG) content, relative gene expression measured by RT-PCR, and histological analyses. Results The MRI index and NP area of injured discs of glucosamine treated animals with annular puncture was found to be lower than that of degenerated discs from rabbits not supplemented with glucosamine. Consistent with this, decreased glycosaminoglycan was demonstrated in glucosamine fed animals, as determined by both histological and GAG content. Gene expression was consistent with a detrimental effect on matrix. Conclusions These data demonstrate that the net effect on matrix in an animal model in vivo, as measured by gene expression, MRI, histology, and total proteoglycan is anti-anabolic. This raises concern over this commonly used supplement, and future research is needed to establish the clinical relevance of these findings. PMID:23324939

Artificial Cervical Vertebra and Intervertebral Complex Replacement through the Anterior Approach in Animal Model: A Biomechanical and In Vivo Evaluation of a Successful Goat Model

PubMed Central

Qin, Jie; He, Xijing; Wang, Dong; Qi, Peng; Guo, Lei; Huang, Sihua; Cai, Xuan; Li, Haopeng; Wang, Rui

2012-01-01

This was an in vitro and in vivo study to develop a novel artificial cervical vertebra and intervertebral complex (ACVC) joint in a goat model to provide a new method for treating degenerative disc disease in the cervical spine. The objectives of this study were to test the safety, validity, and effectiveness of ACVC by goat model and to provide preclinical data for a clinical trial in humans in future. We designed the ACVC based on the radiological and anatomical data on goat and human cervical spines, established an animal model by implanting the ACVC into goat cervical spines in vitro prior to in vivo implantation through the anterior approach, and evaluated clinical, radiological, biomechanical parameters after implantation. The X-ray radiological data revealed similarities between goat and human intervertebral angles at the levels of C2-3, C3-4, and C4-5, and between goat and human lordosis angles at the levels of C3-4 and C4-5. In the in vivo implantation, the goats successfully endured the entire experimental procedure and recovered well after the surgery. The radiological results showed that there was no dislocation of the ACVC and that the ACVC successfully restored the intervertebral disc height after the surgery. The biomechanical data showed that there was no significant difference in range of motion (ROM) or neural zone (NZ) between the control group and the ACVC group in flexion-extension and lateral bending before or after the fatigue test. The ROM and NZ of the ACVC group were greater than those of the control group for rotation. In conclusion, the goat provides an excellent animal model for the biomechanical study of the cervical spine. The ACVC is able to provide instant stability after surgery and to preserve normal motion in the cervical spine. PMID:23300816

Assessment of Intervertebral Disc Degeneration Based on Quantitative MRI Analysis: an in vivo study

PubMed Central

Grunert, Peter; Hudson, Katherine D.; Macielak, Michael R.; Aronowitz, Eric; Borde, Brandon H.; Alimi, Marjan; Njoku, Innocent; Ballon, Douglas; Tsiouris, Apostolos John; Bonassar, Lawrence J.; Härtl, Roger

2015-01-01

Study design Animal experimental study Objective To evaluate a novel quantitative imaging technique for assessing disc degeneration. Summary of Background Data T2-relaxation time (T2-RT) measurements have been used to quantitatively assess disc degeneration. T2 values correlate with the water content of inter vertebral disc tissue and thereby allow for the indirect measurement of nucleus pulposus (NP) hydration. Methods We developed an algorithm to subtract out MRI voxels not representing NP tissue based on T2-RT values. Filtered NP voxels were used to measure nuclear size by their amount and nuclear hydration by their mean T2-RT. This technique was applied to 24 rat-tail intervertebral discs’ (IVDs), which had been punctured with an 18-gauge needle according to different techniques to induce varying degrees of degeneration. NP voxel count and average T2-RT were used as parameters to assess the degeneration process at 1 and 3 months post puncture. NP voxel counts were evaluated against X-ray disc height measurements and qualitative MRI studies based on the Pfirrmann grading system. Tails were collected for histology to correlate NP voxel counts to histological disc degeneration grades and to NP cross-sectional area measurements. Results NP voxel count measurements showed strong correlations to qualitative MRI analyses (R2=0.79, p<0.0001), histological degeneration grades (R2=0.902, p<0.0001) and histological NP cross-sectional area measurements (R2=0.887, p<0.0001). In contrast to NP voxel counts, the mean T2-RT for each punctured group remained constant between months 1 and 3. The mean T2-RTs for the punctured groups did not show a statistically significant difference from those of healthy IVDs (63.55ms ±5.88ms month 1 and 62.61ms ±5.02ms) at either time point. Conclusion The NP voxel count proved to be a valid parameter to quantitatively assess disc degeneration in a needle puncture model. The mean NP T2-RT does not change significantly in needle-puncture induced degenerated IVDs. IVDs can be segmented into different tissue components according to their innate T2-RT. PMID:24384655

Running exercise strengthens the intervertebral disc

PubMed Central

Belavý, Daniel L.; Quittner, Matthew J.; Ridgers, Nicola; Ling, Yuan; Connell, David; Rantalainen, Timo

2017-01-01

There is currently no evidence that the intervertebral discs (IVDs) can respond positively to exercise in humans. Some authors have argued that IVD metabolism in humans is too slow to respond anabolically to exercise within the human lifespan. Here we show that chronic running exercise in men and women is associated with better IVD composition (hydration and proteoglycan content) and with IVD hypertrophy. Via quantitative assessment of physical activity we further find that accelerations at fast walking and slow running (2 m/s), but not high-impact tasks, lower intensity walking or static positions, correlated to positive IVD characteristics. These findings represent the first evidence in humans that exercise can be beneficial for the IVD and provide support for the notion that specific exercise protocols may improve IVD material properties in the spine. We anticipate that our findings will be a starting point to better define exercise protocols and physical activity profiles for IVD anabolism in humans. PMID:28422125

Computation models simulating notochordal cell extinction during early ageing of an intervertebral disc.

PubMed

Louman-Gardiner, K M; Coombe, D; Hunter, C J

2011-12-01

Lower back pain due to intervertebral disc (IVD) degeneration is a prevalent problem which drastically affects the quality of life of millions of sufferers. Healthy IVDs begin with high populations of notochordal cells in the nucleus pulposus, while by the second stage of degeneration, these cells will be replaced by chondrocyte-like cells. Because the IVD is avascular, these cells rely on passive diffusion of nutrients to survive. It is thought that this transition in cell phenotype causes the shift of the IVD's physical properties, which impede the flow of nutrients. Our computational model of the IVD illustrates its ability to simulate the evolving chemical and mechanical environments occurring during the early ageing process. We demonstrate that, due to the insufficient nutrient supply and accompanying changes in physical properties of the IVD, there was a resultant exponential decay in the number of notochordal cells over time.

The Application of Fiber-Reinforced Materials in Disc Repair

PubMed Central

Pei, Bao-Qing; Li, Hui; Zhu, Gang; Li, De-Yu; Fan, Yu-Bo; Wu, Shu-Qin

2013-01-01

The intervertebral disc degeneration and injury are the most common spinal diseases with tremendous financial and social implications. Regenerative therapies for disc repair are promising treatments. Fiber-reinforced materials (FRMs) are a kind of composites by embedding the fibers into the matrix materials. FRMs can maintain the original properties of the matrix and enhance the mechanical properties. By now, there are still some problems for disc repair such as the unsatisfied static strength and dynamic properties for disc implants. The application of FRMs may resolve these problems to some extent. In this review, six parts such as background of FRMs in tissue repair, the comparison of mechanical properties between natural disc and some typical FRMs, the repair standard and FRMs applications in disc repair, and the possible research directions for FRMs' in the future are stated. PMID:24383057

Effects of radial compression on a novel simulated intervertebral disc-like assembly using bone marrow-derived mesenchymal stem cell cell-sheets for annulus fibrosus regeneration.

PubMed

See, Eugene Yong-Shun; Toh, Siew Lok; Goh, James Cho-Hong

2011-10-01

The aim of this study was to develop a tissue engineering approach in regenerating the annulus fibrosus (AF) as part of an overall strategy to produce a tissue-engineered intervertebral disc (IVD) replacement. To determine whether a rehabilitative simulation regime on bone marrow–derived mesenchymal stem cell cell-sheet is able to aid the regeneration of the AF. No previous study has used bone marrow–derived mesenchymal stem cell cell-sheets simulated by a rehabilitative regime to regenerate the AF. The approach was to use bone marrow–derived stem cells to form cell-sheets and incorporating them onto silk scaffolds to simulate the native lamellae of the AF. The in vitro experimental model used to study the efficacy of such a system was made up of the tissue engineering AF construct wrapped around a silicone disc to form a simulated IVD-like assembly. The assembly was cultured within a custom-designed bioreactor that provided a compressive mechanical stimulation onto the silicone disc. The silicone nucleus pulposus would bulge radially and compress the simulated AF to mimic the physiological conditions. The simulated IVD-like assembly was compressed using a rehabilitative regime that lasted for 4 weeks at 0.25 Hz, for 15 minutes each day. With the rehabilitative regime, the cell-sheets remained viable but showed a decrease in cell numbers and viability. Gene expression analysis showed significant upregulation of IVD-related genes and there was an increased ratio of collagen type II to collagen type I found within the extracellular matrix. The results suggested that a rehabilitative regime caused extensive remodeling to take place within the simulated IVD-like assembly, producing extracellular matrix similar to that found in the inner AF.

Development and Implementation of a Transversely Isotropic Hyperelastic Constitutive Model With Two Fiber Families to Represent Anisotropic Soft Biological Tissues

DTIC Science & Technology

2014-06-01

brain tissue and skeletal muscles , is also discussed. transversely isotropic hyperelastic, two fiber families, nearly incompressible, anisotropic...comprised of fibrous structures, such as muscles , ligaments, tendons, intervertebral discs and the brain, often exhibit strong anisotropy along these fiber ...directions, e.g., collagen fibers of the cornea, striated muscle fibers in skeletal muscles , multiple axonal directions within the brain. In each case

Catabolic Effects of Endothelial Cell-Derived Microparticles on Disc Cells: Implications in Intervertebral Disc Neovascularization and Degeneration

PubMed Central

Pohl, Pedro H. I.; Lozito, Thomas P.; Cuperman, Thais; Yurube, Takashi; Moon, Hong J.; Ngo, Kevin; Tuan, Rocky S.; Croix, Claudette St.; Sowa, Gwendolyn A.; Rodrigues, Luciano M. R.; Kang, James D.; Vo, Nam V.

2017-01-01

Neovascularization of intervertebral discs, a phenomenon considered pathological since normal discs are primarily avascular structures, occurs most frequently in annulus fibrosus (AF) of degenerated discs. Endothelial cells (ECs) are involved in this process, but the mechanism of the interaction between AF and endothelial cells is unclear. In this study we evaluated the effects on matrix catabolic activity of AF cells by the extracellular endothelial microparticles (EMPs) and soluble protein factors (SUP fraction) produced from ECs. Passage 1 human AF cells grown in monolayer cultures were treated for 72 hours with 250μg of EMPs or SUP fraction isolated from culture of the microvascular endothelial cell line, HEMC-I. Live-cell imaging revealed uptake of EMPs by AF cells. RT-PCR analysis demonstrated increased mRNA expression of MMP-1 (50.3 fold), MMP-3 (4.5 fold) and MMP-13 (5.5 fold) in AF cell cultures treated with EMPs compared to untreated control. Western analysis also demonstrated increased MMP protein expression in EMP-treated AF cells. AF cells treated with the SUP fraction also exhibited a dramatic increase in MMP mRNA and protein expression. Increased MMP expression is primarily due to EMP or SUP stimulation of AF cells since EMPs or SUP fraction alone contained negligible amount of MMPs. Interestingly, MMP activity was elevated in AF cell cultures treated with EMPs but not with SUP. This study revealed enhanced matrix catabolism as a molecular consequence of action of ECs on AF cells via EMPs, which might be expected during neo-angiogenesis of degenerating disc. PMID:27246627

Detection of low back pain using pH level-dependent imaging of the intervertebral disc using the ratio of R1ρ dispersion and -OH chemical exchange saturation transfer (RROC).

PubMed

Liu, Qi; Tawackoli, Wafa; Pelled, Gadi; Fan, Zhaoyang; Jin, Ning; Natsuaki, Yutaka; Bi, Xiaoming; Gart, Avrom; Bae, Hyun; Gazit, Dan; Li, Debiao

2015-03-01

Low pH is associated with intervertebral disc (IVD)-generated low back pain (LBP). The purpose of this work was to develop an in vivo pH level-dependent magnetic resonance imaging (MRI) method for detecting discogenic LBP, without using exogenous contrast agents. The ratio of R1ρ dispersion and chemical exchange saturation transfer (CEST) (RROC) was used for pH-level dependent imaging of the IVD while eliminating the effect of labile proton concentration. The technique was validated by numerical simulations and studies on phantoms and ex vivo porcine spines. Four male (ages 42.8 ± 18.3) and two female patients (ages 55.5 ± 2.1) with LBP and scheduled for discography were examined with the method on a 3.0 Tesla MR scanner. RROC measurements were compared with discography outcomes using paired t-test. Simulation and phantom results indicated RROC is a concentration independent and pH level-dependent technique. Porcine spine study results found higher RROC value was related to lower pH level. Painful discs based on discography had significant higher RROC values than those with negative diagnosis (P < 0.05). RROC imaging is a promising pH level dependent MRI technique that has the potential to be a noninvasive imaging tool to detect painful IVDs in vivo. © 2014 Wiley Periodicals, Inc.

Canine intervertebral disc disease: a review of etiologic and predisposing factors.

PubMed

Verheijen, J; Bouw, J

1982-01-01

In this report the literature on etiologic and predisposing factors of disc disease in the dog is reviewed and discussed. Hypochondroplasia is considered to be important in the etiology of disc disease. After some consideration on nomenclature and morphology, the genetic background of hypochondroplasia is described. The histochemical morphological and developmental similarities and differences between and within various dog breeds are discussed. Macroscopically visible features that predispose to disc disease are outlined. The biomechanical bow-string model of the vertebral column is reviewed. In the discussion the various literature data are interrelated to show how disc disease might be reduced by breeding measures without implicating the breed characteristics. Literature recommendations to help the individual dog are included.

A potential role for cell-based therapeutics in the treatment of intervertebral disc herniation.

PubMed

Ganey, Timothy M; Meisel, Hans Joerg

2002-10-01

Lower back pain and disc degeneration negatively affect quality of life and impose an enormous financial burden. An extensive body of scientific work has evolved that characterizes the disc, demonstrating spinal anatomy and morphology that contribute to risk and likely promote failure. Ultimately, matrix failure is responsible for mechanical failure, which in turn results in spinal compromise anatomically and subsequent pain. One intervening approach to breaking this sequence has been to repopulate the anatomy with autologous disc chondrocytes--cells capable of restoring the matrix and retaining the mechanical balance by which the disc functions. This strategy has been implemented both in patients and in animal models, and early results, although preliminary, support the premise as a positive approach.

2D segmentation of intervertebral discs and its degree of degeneration from T2-weighted magnetic resonance images

NASA Astrophysics Data System (ADS)

Castro-Mateos, Isaac; Pozo, José Maria; Lazary, Aron; Frangi, Alejandro F.

2014-03-01

Low back pain (LBP) is a disorder suffered by a large population around the world. A key factor causing this illness is Intervertebral Disc (IVD) degeneration, whose early diagnosis could help in preventing this widespread condition. Clinicians base their diagnosis on visual inspection of 2D slices of Magnetic Resonance (MR) images, which is subject to large interobserver variability. In this work, an automatic classification method is presented, which provides the Pfirrmann degree of degeneration from a mid-sagittal MR slice. The proposed method utilizes Active Contour Models, with a new geometrical energy, to achieve an initial segmentation, which is further improved using fuzzy C-means. Then, IVDs are classified according to their degree of degeneration. This classification is attained by employing Adaboost on five specific features: the mean and the variance of the probability map of the nucleus using two different approaches and the eccentricity of the fitting ellipse to the contour of the IVD. The classification method was evaluated using a cohort of 150 intervertebral discs assessed by three experts, resulting in a mean specificity (93%) and sensitivity (83%) similar to the one provided by every expert with respect to the most voted value. The segmentation accuracy was evaluated using the Dice Similarity Index (DSI) and Root Mean Square Error (RMSE) of the point-to-contour distance. The mean DSI ± 2 standard deviation was 91:7% ±5:6%, the mean RMSE was 0:82mm and the 95 percentile was 1:36mm. These results were found accurate when compared to the state-of-the-art.

The serine proteinase inhibitory proteins of the chondrodystrophoid (beagle) and non-chondrodystrophoid (greyhound) canine intervertebral disc.

PubMed

Melrose, J; Taylor, T K; Ghosh, P

1997-06-01

Trypsin inhibitory proteins of low buoyant density (p < or = 1.35 g/mL) fractions were prepared by CsCl density gradient ultracentrifugation of 4 M guanidinium hydrochloride extracts of lumbar beagle and greyhound annulus fibrosus and nucleus pulposus from animals aged 1 to 6 years. Affinity blotting with biotinylated trypsin was used to identify active trypsin inhibitory protein species; these species were also identified immunologically by Western blotting using antibodies against bovine pancreatic trypsin inhibitor (BPTI), and human inter-alpha-trypsin inhibitor (ITI). None of the trypsin inhibitory species evident in Western blots were reactive with anti-human alpha1-proteinase inhibitor (alpha-1-PI), alpha2-macroglobulin or secretory leucocyte proteinase inhibitor. The greyhound intervertebral disc samples generally had higher levels of active trypsin inhibitor species per unit weight of tissue extracted, and a more extensive range of inhibitor species. Inhibitor species of 30, 32, 34 kDa were identified in both beagle and greyhound intervertebral disc samples; these species were generally most prominent in the annulus fibrosus samples. In contrast, the nucleus pulposus samples contained relatively large trypsin inhibitor species; the anti-BPTI detected an inhibitor species of approximately 85-90 kDa; anti-ITI detected species of 120-250 kDa; biotinylated trypsin detected species of 60-110 kDa. A small molecular mass trypsin inhibitor species of 6 kDa, which was of similar mobility to BPTI, was also detected in annulus fibrosus samples; however, this species did not react with anti-BPTI.

Ulf Fernström (1915-1985) and his Contributions to the Development of Artificial Disc Replacements.

PubMed

Fisahn, Christian; Burgess, Brittni; Iwanaga, Joe; Chapman, Jens R; Oskouian, Rod J; Tubbs, R Shane

2017-02-01

Artificial disc replacements, which serve the function of separating vertebrae to allow for proper spinal alignment, can help treat debilitating low back pain in patients who have failed other conservative methods of treatment. A Swedish surgeon, Ulf Fernström, was the pioneer of artificial disc replacement, and his contribution in the form of Fernström balls dramatically altered spinal surgery and technique by showing the proper technique and implant that should be used for areas requiring motion in many planes. Ulf Fernström created his artificial disc inspired by the movement of the hip and knee joints. His implants attempted to restore disc spacing and articulation in patients who had failed conservative measures of treatment. Fernström balls were the first implants of their kind and represent the first attempt at artificial disc replacement. However, many surgeons and researchers questioned Fernström balls, claiming that their lack of elastic properties could damage patients. Of the wide range of implants on the market for the intervertebral disc space, all designs and applications of products stem from the initial discovery made by Fernström, thus making him a pioneer in disc replacement. Copyright © 2016 Elsevier Inc. All rights reserved.

Active Duty Access to Specialty Care Within the Great Plains Regional Medical Command: A Cost Benefit Analysis

DTIC Science & Technology

1998-06-01

Spondylosis of unspecified site without mention of myelopathy Scar conditions and fibrosis of skin Lumbar intervertebral disc without myelopathy Table 16...SOOH 20 HAND SURGERY MMU 17 PULMONARY DISEASE SOOL 13 DISC SURGERY ( LUMBAR ) MMC 12 CARDIOLOGY SSO 11 OPTHAMOLOGY MMR 10 RHEUMATOLOGY (Froom...SSU 56 Urology MMG 44 Gastroenterology MMC 43 Cardiology SOOL 43 Disk Surgery ( Lumbar ) SSR 42 Otorhinolaryngology MMO 37 Oncology (Medical) MMU

A Baseline Historical Analysis of Neck and Back-Related Morbidity in the U.S. Army: Occupational Risks Potentially Related to Head-Supported Mass

DTIC Science & Technology

2005-09-01

disorder with myelopathy, unspecified region 722.73 Intervertebral disc disorder w/ myelopathy, lumbar region 721.3 Lumbosacral spondylosis without...Disc disorder, lumbar region 721.42 Spondylosis with myelopathy, lumbar region 724.6 Disorders of sacrum 738.4 Acquired spondylolisthesis...particular, increases risk for spondylosis and accentuates age-related decreases in spinal lordosis(20). In addition to the ballistic protection

Expression of receptors for putative anabolic growth factors in human intervertebral disc: implications for repair and regeneration of the disc.

PubMed

Le Maitre, Christine L; Richardson, Stephen M A; Baird, Pauline; Freemont, Anthony J; Hoyland, Judith A

2005-12-01

Low back pain (LBP) is a common, debilitating and economically important disorder. Current evidence implicates loss of intervertebral disc (IVD) matrix consequent upon 'degeneration' as a major cause of LBP. Degeneration of the IVD involves increases in degradative enzymes and decreases in the extracellular matrix (ECM) component in a process that is controlled by a range of cytokines and growth factors. Studies have suggested using anabolic growth factors to regenerate the normal matrix of the IVD, hence restoring disc height and reversing degenerative disc disease. However, for such therapies to be successful it is vital that the target cells (i.e. the disc cells) express the appropriate receptors. This immunohistochemical study has for the first time investigated the expression and localization of four potentially beneficial growth factor receptors (i.e. TGFbetaRII, BMPRII, FGFR3 and IGFRI) in non-degenerate and degenerate human IVDs. Receptor expression was quantified across regions of the normal and degenerate disc and showed that cells of the nucleus pulposus (NP) and inner annulus fibrosus (IAF) expressed significantly higher levels of the four growth factor receptors investigated. There were no significant differences between the four growth factor expression in non-degenerate and degenerate biopsies. However, expression of TGFbetaRII, FGFR3 and IGFRI, but not BMP RII, were observed in the ingrowing blood vessels that characterize part of the disease aetiology. In conclusion, this study has demonstrated the expression of the four growth factor receptors at similar levels in the chondrocyte-like cells of the NP and IAF in both non-degenerate and degenerate discs, implicating a role in normal disc homeostasis and suggesting that the application of these growth factors to the degenerate human IVD would stimulate matrix production. However, the expression of some of the growth factor receptors on ingrowing blood vessels might be problematic in a therapeutic approach. Copyright 2005 Pathological Society of Great Britain and Ireland.

C-130J Human Vibration

DTIC Science & Technology

2005-08-01

Hulshof , 1999; Dupuis & Zerlett, 1986; Kittusamy & Buchholz, 2004; Seidel, 1993). There is also evidence of intervertebral disc problems and...Bovenzi, M., & Hulshof , C.T.J. (1999). An updated review of epidemiologic studies on the relationship between exposure to whole-body vibration and

Development of injectable hydrogels for nucleus pulposus replacement

NASA Astrophysics Data System (ADS)

Thomas, Jonathan D.

Intervertebral disc degeneration has been reported as the underlying cause for 75% of cases of lower back pain and is marked by dehydration of the nucleus pulposus within the intervertebral disc. There have been many implant designs to replace the nucleus pulposus. Some researchers have proposed the replacement of the nucleus pulposus with hydrogel materials. The insertion of devices made from these materials further compromises the annulus of the disc. An ideal nucleus replacement could be injected into the disc space and form a solid in vivo. However, injectable replacements using curing elastomers and thermoplastic materials are not ideal because of the potentially harmful exothermic heat evolved from their reactions and the toxicity of the reactants used. We propose a hydrogel system that can be injected as a liquid at 25°C and solidified to yield a hydrogel within the intervertebral disc at 37°C. In aqueous solutions, these polymers have Lower Critical Solution Temperatures (LCST) between 25-37°C, making them unique candidate materials for this application. Poly(N-isopropylacrylamide) (PNIPAAm) is the most widely studied LCST polymer due to its drastic transition near body temperature. However, by itself, pure PNIPAAm forms a hydrogel that has low water content and can readily undergo plastic deformation. To increase the water content and impart elasticity to PNIPAAm hydrogels, grafted and branched hydrogel systems were created that incorporated the thermogelling PNIPAAm and hydrophilic poly(ethylene glycol) (PEG). In this research, the effects of polymer composition and monomer to initiator ratio, which controls polymer MW, on the in vitro swelling properties (mass, chemical, and compressive mechanical stability) of hydrogels formed from aqueous solutions of these polymers were evaluated. Immersion studies were also conducted in solutions to simulate the osmotic environment of the nucleus pulposus. The effects of repeated compression and unloading cycles on the water content and dimensional recovery of hydrogels made from three candidate polymer formulations were also determined. Unlike PNIPAAm and PEG grafted PNIPAAm hydrogels, PEG branched hydrogels have covalently linked networks. Addition of 7 mol% PEG branches to PNIPAAm resulted in a hydrogel with a higher water content and better elastic recovery than hydrogels made from pure PNIPAAm. PEG branched PNIPAAm hydrogels were shown to have mass, chemical, and compressive mechanical stability in vitro. Furthermore, these hydrogels showed superior dimensional recovery after compressive cycling than pure PNIPAAm and PEG grafted PNIPAAm hydrogels. The 7 mol% PEG branched PNIPAAm hydrogels have suitable swelling and mechanical properties to potentially serve as a nucleus pulposus replacement.

Biomechanical implications of lumbar spinal ligament transection.

PubMed

Von Forell, Gregory A; Bowden, Anton E

2014-11-01

Many lumbar spine surgeries either intentionally or inadvertently damage or transect spinal ligaments. The purpose of this work was to quantify the previously unknown biomechanical consequences of isolated spinal ligament transection on the remaining spinal ligaments (stress transfer), vertebrae (bone remodelling stimulus) and intervertebral discs (disc pressure) of the lumbar spine. A finite element model of the full lumbar spine was developed and validated against experimental data and tested in the primary modes of spinal motion in the intact condition. Once a ligament was removed, stress increased in the remaining spinal ligaments and changes occurred in vertebral strain energy, but disc pressure remained similar. All major biomechanical changes occurred at the same spinal level as the transected ligament, with minor changes at adjacent levels. This work demonstrates that iatrogenic damage to spinal ligaments disturbs the load sharing within the spinal ligament network and may induce significant clinically relevant changes in the spinal motion segment.

MRI signal distribution within the intervertebral disc as a biomarker of adolescent idiopathic scoliosis and spondylolisthesis.

PubMed

Gervais, Julien; Périé, Delphine; Parent, Stefan; Labelle, Hubert; Aubin, Carl-Eric

2012-12-03

Early stages of scoliosis and spondylolisthesis entail changes in the intervertebral disc (IVD) structure and biochemistry. The current clinical use of MR T2-weighted images is limited to visual inspection. Our hypothesis is that the distribution of the MRI signal intensity within the IVD in T2-weighted images depends on the spinal pathology and on its severity. Therefore, this study aims to develop the AMRSID (analysis of MR signal intensity distribution) method to analyze the 3D distribution of the MR signal intensity within the IVD and to evaluate their sensitivity to scoliosis and spondylolisthesis and their severities. This study was realized on 79 adolescents who underwent a MRI acquisition (sagittal T2-weighted images) before their orthopedic or surgical treatment. Five groups were considered: low severity scoliosis (Cobb angle ≤50°), high severity scoliosis (Cobb angles >50°), low severity spondylolisthesis (Meyerding grades I and II), high severity spondylolisthesis (Meyerding grades III, IV and V) and control. The distribution of the MRI signal intensity within the IVD was analyzed using the descriptive statistics of histograms normalized by either cerebrospinal fluid or bone signal intensity, weighted centers and volume ratios. Differences between pathology and severity groups were assessed using one- and two-way ANOVAs. There were significant (p < 0.05) variations of indices between scoliosis, spondylolithesis and control groups and between low and high severity groups. The cerebrospinal fluid normalization was able to detect differences between healthy and pathologic IVDs whereas the bone normalization, which reflects both bone and IVD health, detected more differences between the severities of these pathologies. This study proves for the first time that changes in the intervertebral disc, non visible to the naked eye on sagittal T2-weighted MR images of the spine, can be detected from specific indices describing the distribution of the MR signal intensity. Moreover, these indices are able to discriminate between scoliosis and spondylolisthesis and their severities, and provide essential information on the composition and structure of the discs whatever the pathology considered. The AMRSID method may have the potential to complement the current diagnostic tools available in clinics to improve the diagnostic with earlier biomarkers, the prognosis of evolution and the treatment options of scoliosis and spondylolisthesis.

Optimal Spectral Regions For Laser Excited Fluorescence Diagnostics For Point Of Care Application

NASA Astrophysics Data System (ADS)

Vaitkuviene, A.; Gėgžna, V.; Varanius, D.; Vaitkus, J.

2011-09-01

The tissue fluorescence gives the response of light emitting molecule signature, and characterizes the cell composition and peculiarities of metabolism. Both are useful for the biomedical diagnostics, as reported in previous our and others works. The present work demonstrates the results of application of laser excited autofluorescence for diagnostics of pathology in genital tissues, and the feasibility for the bedside at "point of care—off lab" application. A portable device using the USB spectrophotometer, micro laser (355 nm Nd:YAG, 0,5 ns pulse, repetition rate 10 kHz, output power 15 mW), three channel optical fiber and computer with diagnostic program was designed and ready for clinical trial to be used for cytology and biopsy specimen on site diagnostics, and for the endoscopy/puncture procedures. The biopsy and cytology samples, as well as intervertebral disc specimen were evaluated by pathology experts and the fluorescence spectra were investigated in the fresh and preserved specimens. The spectra were recorded in the spectral range 350-900 nm. At the initial stage the Gaussian components of spectra were found and the Mann-Whitney test was used for the groups' differentiation and the spectral regions for optimal diagnostics purpose were found. Then a formal dividing of spectra in the components or the definite width bands, where the main difference of the different group spectra was observed, was used to compare these groups. The ROC analysis based diagnostic algorithms were created for medical prognosis. The positive prognostic values and negative prediction values were determined for cervical Liquid PAP smear supernatant sediment diagnosis of being Cervicitis and Norma versus CIN2+. In a case of intervertebral disc the analysis allows to get the additional information about the disc degeneration status. All these results demonstrated an efficiency of the proposed procedure and the designed device could be tested at the point-of-care site or for intervertebral disc operations.

Quantitative Discomanometry: Correlation of Intradiscal Pressure Values to Pain Reduction in Patients With Intervertebral Disc Herniation Treated With Percutaneous, Minimally Invasive, Image-Guided Techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Filippiadis, Dimitrios K., E-mail: dfilippiadis@yahoo.gr; Mazioti, A., E-mail: argyromazioti@yahoo.gr; Papakonstantinou, O., E-mail: sogofianol@gmail.com

Purpose: To illustrate quantitative discomanometry's (QD) diagnostic efficacy and predictive value in discogenic-pain evaluation in a prospective study correlating intradiscal pressure values with pain reduction after percutaneous image-guided technique (i.e., percutaneous decompression, PD). Materials and Methods: During the last 3 years, 36 patients [21 male and 15 female (mean age 36 {+-} 5.8 years)] with intervertebral disc hernia underwent QD before PD. Under absolute sterilization and fluoroscopy, a mixture of contrast medium and normal saline (3:1 ratio) was injected. A discmonitor performed a constant rate injection and recorded pressure and volume values, thus producing the relative pressure-volume curve. PD wasmore » then performed. Pain reduction and improved mobility were recorded at 3, 12, and 24 months after PD using clinical evaluation and a numeric visual scale (NVS; 0 to 10 units). Results: Mean pain values of 7.5 {+-} 1.9 (range 4 to 8) NVS units were recorded before PD; these decreased to 2.9 {+-} 2.44 at 3 months, 1.0 {+-} 1.9 at 12 months, and 1.0 {+-} 1.9 NVS units at 24 months after PD. Recorded correlations (pressure, volume, significant pain-reduction values) with bilateral statistical significance included a maximum injected volume of 2.4 ml (p = 0.045), P{sub o} < 14 psi [initial pressure required to inject 0.1 ml of the mixture inside the disc (p = 0.05)], P{sub max} {<=} 65 psi [greatest pressure value on the curve (p = 0.018)], and P{sub max} - P{sub o} {<=} 47 psi (p = 0.038). Patients meeting these pressure or volume cut-off points, either independently or as a total, had significant pain reduction (>4 NVS units) after PD. No complications were noted. Conclusions: QD is an efficient technique that may have predictive value for discogenic pain evaluation. It might serve as a useful tool for patient selection for intervertebral disc therapies.« less

A comparison between porcine, ovine, and bovine intervertebral disc anatomy and single lamella annulus fibrosus tensile properties.

PubMed

Monaco, Lauren A; DeWitte-Orr, Stephanie J; Gregory, Diane E

2016-02-01

This project aimed to compare gross anatomical measures and biomechanical properties of single lamellae from the annulus fibrosus of ovine and porcine lumbar vertebrae, and bovine tail vertebrae. The morphology of the vertebrae of these species differ significantly both from each other and from human, yet how these differences alter biomechanical properties is unknown. Geometric parameters measured in this study included: 1) absolute and relative intervertebral (IVD) and vertebral body height and 2) absolute and relative intervertebral disc (IVD) anterior-posterior (AP) and medial-lateral (ML) widths. Single lamella tensile properties included toe-region stress and stretch ratio, stiffness, and tensile strength. As expected, the bovine tail IVD revealed a more circular shape compared with both the ovine and porcine lumbar IVD. The bovine tail also had the largest IVD to vertebral body height ratio (due to having the highest absolute IVD height). Bovine tail lamellae were also found to be strongest and stiffest (in tension) while ovine lumbar lamellae were weakest and most compliant. Histological analysis revealed the greatest proportion of collagen in the bovine corroborating findings of increased strength and stiffness. The observed differences in anatomical shape, connective tissue composition, and tensile properties need to be considered when choosing an appropriate model for IVD research. © 2015 Wiley Periodicals, Inc.

Injection of AAV2-BMP2 and AAV2-TIMP1 into the nucleus pulposus slows the course of intervertebral disc degeneration in an in vivo rabbit model.

PubMed

Leckie, Steven K; Bechara, Bernard P; Hartman, Robert A; Sowa, Gwendolyn A; Woods, Barrett I; Coelho, Joao P; Witt, William T; Dong, Qing D; Bowman, Brent W; Bell, Kevin M; Vo, Nam V; Wang, Bing; Kang, James D

2012-01-01

Intervertebral disc degeneration (IDD) is a common cause of back pain. Patients who fail conservative management may face the morbidity of surgery. Alternative treatment modalities could have a significant impact on disease progression and patients' quality of life. To determine if the injection of a virus vector carrying a therapeutic gene directly into the nucleus pulposus improves the course of IDD. Prospective randomized controlled animal study. Thirty-four skeletally mature New Zealand white rabbits were used. In the treatment group, L2-L3, L3-L4, and L4-L5 discs were punctured in accordance with a previously validated rabbit annulotomy model for IDD and then subsequently treated with adeno-associated virus serotype 2 (AAV2) vector carrying genes for either bone morphogenetic protein 2 (BMP2) or tissue inhibitor of metalloproteinase 1 (TIMP1). A nonoperative control group, nonpunctured sham surgical group, and punctured control group were also evaluated. Serial magnetic resonance imaging (MRI) studies at 0, 6, and 12 weeks were obtained, and a validated MRI analysis program was used to quantify degeneration. The rabbits were sacrificed at 12 weeks, and L4-L5 discs were analyzed histologically. Viscoelastic properties of the L3-L4 discs were analyzed using uniaxial load-normalized displacement testing. Creep curves were mathematically modeled according to a previously validated two-phase exponential model. Serum samples obtained at 0, 6, and 12 weeks were assayed for biochemical evidence of degeneration. The punctured group demonstrated MRI and histologic evidence of degeneration as expected. The treatment groups demonstrated less MRI and histologic evidence of degeneration than the punctured group. The serum biochemical marker C-telopeptide of collagen type II increased rapidly in the punctured group, but the treated groups returned to control values by 12 weeks. The treatment groups demonstrated several viscoelastic properties that were distinct from control and punctured values. Treatment of punctured rabbit intervertebral discs with AAV2-BMP2 or AAV2-TIMP1 helps delay degenerative changes, as seen on MRI, histologic sampling, serum biochemical analysis, and biomechanical testing. Although data from animal models should be extrapolated to the human condition with caution, this study supports the potential use of gene therapy for the treatment of IDD. Copyright © 2012 Elsevier Inc. All rights reserved.

Automatic diagnosis of lumbar disc herniation with shape and appearance features from MRI

NASA Astrophysics Data System (ADS)

Alomari, Raja'S.; Corso, Jason J.; Chaudhary, Vipin; Dhillon, Gurmeet

2010-03-01

Intervertebral disc herniation is a major reason for lower back pain (LBP), which is the second most common neurological ailment in the United States. Automation of herniated disc diagnosis reduces the large burden on radiologists who have to diagnose hundreds of cases each day using clinical MRI. We present a method for automatic diagnosis of lumbar disc herniation using appearance and shape features. We jointly use the intensity signal for modeling the appearance of herniated disc and the active shape model for modeling the shape of herniated disc. We utilize a Gibbs distribution for classification of discs using appearance and shape features. We use 33 clinical MRI cases of the lumbar area for training and testing both appearance and shape models. We achieve over 91% accuracy in detection of herniation in a cross-validation experiment with specificity of 91% and sensitivity of 94%.

A PHASED REHABILITATION PROTOCOL FOR ATHLETES WITH LUMBAR INTERVERTEBRAL DISC HERNIATION

PubMed Central

VanGelder, Leonard H.; Vaughn, Daniel W.

2013-01-01

Conservative non-surgical management of a herniated lumbar intervertebral disc (HLD) in athletes is a complex task due to the dramatic forces imparted on the spine during sport participation. The demands placed upon the athlete during rehabilitation and return to sport are unique not only from a sport specific perspective, but also regarding return to the sport strength and conditioning programs utilized for sport preparation. Many prescriptions fail to address postural and motor control faults specific to athletic development, which may prevent full return to sport after suffering a HLD or predispose the athlete to future exacerbations of a HLD. Strength exercises involving squatting, deadlifting, and Olympic power lifts are large components of the typical athlete's conditioning program, therefore some progressions are provided to address potential underlying problems in the athlete's technique that may have contributed to their HLD in the first place. The purpose of this clinical commentary is to propose a framework for rehabilitation that is built around the phases of healing of the disc. Phase I: Non-Rotational/Non-Flexion Phase (Acute Inflammatory Phase), Phase II: Counter rotation/Flexion Phase (Repair Phase), Phase III: Rotational Phase/Power development (Remodeling Phase), and Phase IV: Full return to sport. This clinical commentary provides a theoretical basis for these phases based on available literature as well as reviewing many popular current practice trends in the management of an HLD. The authors recognize the limits of any general exercise rehabilitation recommendation with regard to return to sport, as well as any general strength and conditioning program. It is vital that an individual assessment and prescription is made for every athlete which reviews and addresses movement in all planes of motion under all necessary extrinsic and intrinsic demands to that athlete. Level of Evidence: 5 PMID:24175134

Can the pattern of vertebral marrow oedema differentiate intervertebral disc infection from degenerative changes?

PubMed

Shrot, S; Sayah, A; Berkowitz, F

2017-07-01

To evaluate whether various patterns of bone marrow oedema could be used to discriminate between infection and degenerative change. Seventy patients with imaging features suspicious for discitis and available clinical follow-up were blindly reviewed for vertebral marrow oedema on sagittal short-tau inversion recovery (STIR) images according to the following patterns: I, vertebra oedema is adjacent to the intervertebral space and sharply-marginated; II, vertebral oedema is adjacent to the intervertebral space but not sharply marginated from normal marrow or involves the entire vertebral body; and III, vertebral oedema is distant from the endplate with intervening hypointense marrow signal. Of 45 patients with a clinical diagnosis of discitis, pattern II was the most common oedema pattern (64%). Approximately 20% and 9% of discitis patients showed patterns I and III, respectively. In patients with degenerative changes, 44% patients showed pattern I, 32% showed pattern II, and 24% showed pattern III. Pattern II had a sensitivity, specificity, and positive predictive value of 0.64, 0.68, and 0.78 for diagnosing spine infection, respectively. Although bone marrow oedema in infective discitis most often extends from the disc space and has indistinct margins, the oedema may also have sharp margins or be remote from the involved intervertebral space. Bone marrow oedema patterns of infective discitis overlap with those of degenerative disease and are not sufficiently reliable to exclude infection in cases with magnetic resonance imaging findings suggestive of discitis. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Minimally invasive photopolymerization in intervertebral disc tissue cavities

NASA Astrophysics Data System (ADS)

Schmocker, Andreas M.; Khoushabi, Azadeh; Gantenbein-Ritter, Benjamin; Chan, Samantha; Bonél, Harald Marcel; Bourban, Pierre-Etienne; Mânson, Jan Anders; Schizas, Constantin; Pioletti, Dominique; Moser, Christophe

2014-03-01

Photopolymerized hydrogels are commonly used for a broad range of biomedical applications. As long as the polymer volume is accessible, gels can easily be hardened using light illumination. However, in clinics, especially for minimally invasive surgery, it becomes highly challenging to control photopolymerization. The ratios between polymerizationvolume and radiating-surface-area are several orders of magnitude higher than for ex-vivo settings. Also tissue scattering occurs and influences the reaction. We developed a Monte Carlo model for photopolymerization, which takes into account the solid/liquid phase changes, moving solid/liquid-boundaries and refraction on these boundaries as well as tissue scattering in arbitrarily designable tissue cavities. The model provides a tool to tailor both the light probe and the scattering/absorption properties of the photopolymer for applications such as medical implants or tissue replacements. Based on the simulations, we have previously shown that by adding scattering additives to the liquid monomer, the photopolymerized volume was considerably increased. In this study, we have used bovine intervertebral disc cavities, as a model for spinal degeneration, to study photopolymerization in-vitro. The cavity is created by enzyme digestion. Using a custom designed probe, hydrogels were injected and photopolymerized. Magnetic resonance imaging (MRI) and visual inspection tools were employed to investigate the successful photopolymerization outcomes. The results provide insights for the development of novel endoscopic light-scattering polymerization probes paving the way for a new generation of implantable hydrogels.

Neuroprotective effects of curcumin alleviate lumbar intervertebral disc degeneration through regulating the expression of iNOS, COX‑2, TGF‑β1/2, MMP‑9 and BDNF in a rat model.

PubMed

Hu, Yuan; Tang, Jin-Shu; Hou, Shu-Xun; Shi, Xiu-Xiu; Qin, Jiang; Zhang, Tie-Song; Wang, Xiao-Jing

2017-11-01

Curcumin is a natural product with antimutagenic, antitumor, antioxidant and neuroprotective properties. However, to the best of our knowledge, curcumin has yet to be investigated for the treatment of lumbar intervertebral disc degeneration LIDD). The aim of the present study was to investigate whether curcumin can alleviate LIDD through regulating the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)‑2, transforming growth factor (TGF)‑β1/2, matrix metalloproteinase (MMP)‑9 and brain‑derived neurotrophic factor (BDNF) in a rat model of LIDD. The results of the present study suggest that pretreatment with curcumin can prevent the development of LIDD in rats. It was revealed that treatment with curcumin significantly reduced interleukin (IL)‑1β and IL‑6, iNOS, COX‑2 and MMP‑9 levels in rats with LIDD. In addition, treatment with curcumin reduced the mRNA expression levels of TGF‑β1 and TGF‑β2, whereas it increased the mRNA expression levels of BDNF in rats with LIDD. In conclusion, the present findings indicate that curcumin may exert protective effects on LIDD development, exerting its action through the regulation of iNOS, COX‑2, TGF‑β1/2, MMP‑9 and BDNF.

Cost-effectiveness of lumbar artificial intervertebral disc replacement: driven by the choice of comparator.

PubMed

Parkinson, Bonny; Goodall, Stephen; Thavaneswaran, Prema

2013-09-01

Lower back pain is a common and costly condition in Australia. This paper aims to conduct an economic evaluation of lumbar artificial intervertebral disc replacement (AIDR) compared with lumbar fusion for the treatment of patients suffering from significant axial back pain and/or radicular (nerve root) pain, secondary to disc degeneration or prolapse, who have failed conservative treatment. A cost-effectiveness approach was used to compare costs and benefits of AIDR to five fusion approaches. Resource use was based on Medicare Benefits Schedule claims data and expert opinion. Effectiveness and re-operation rates were based on published randomized controlled trials. The key clinical outcomes considered were narcotic medication discontinuation, achievement of overall clinical success, achievement of Oswestry Disability Index success and quality-adjusted life-years gained. AIDR was estimated to be cost-saving compared with fusion overall ($1600/patient); however, anterior lumbar interbody fusion and posterolateral fusion were less costly by $2155 and $807, respectively. The incremental cost-effectiveness depends on the outcome considered and the comparator. AIDR is potentially a cost-saving treatment for lumbar disc degeneration, although longer-term follow-up data are required to substantiate this claim. The incremental cost-effectiveness depends on the outcome considered and the comparator, and further research is required before any firm conclusions can be drawn. © 2012 The Authors. ANZ Journal of Surgery © 2012 Royal Australasian College of Surgeons.

Running Exercise Alleviates Pain and Promotes Cell Proliferation in a Rat Model of Intervertebral Disc Degeneration

PubMed Central

Luan, Shuo; Wan, Qing; Luo, Haijie; Li, Xiao; Ke, Songjian; Lin, Caina; Wu, Yuanyuan; Wu, Shaoling; Ma, Chao

2015-01-01

Chronic low back pain accompanied by intervertebral disk degeneration is a common musculoskeletal disorder. Physical exercise, which is clinically recommended by international guidelines, has proven to be effective for degenerative disc disease (DDD) patients. However, the mechanism underlying the analgesic effects of physical exercise on DDD remains largely unclear. The results of the present study showed that mechanical withdrawal thresholds of bilateral hindpaw were significantly decreased beginning on day three after intradiscal complete Freund’s adjuvant (CFA) injection and daily running exercise remarkably reduced allodynia in the CFA exercise group beginning at day 28 compared to the spontaneous recovery group (controls). The hindpaw withdrawal thresholds of the exercise group returned nearly to baseline at the end of experiment, but severe pain persisted in the control group. Histological examinations performed on day 70 revealed that running exercise restored the degenerative discs and increased the cell densities of the annulus fibrosus (AF) and nucleus pulposus (NP). Furthermore, immunofluorescence labeling revealed significantly higher numbers of 5-bromo-2-deoxyuridine (BrdU)-positive cells in the exercise group on days 28, 42, 56 and 70, which indicated more rapid proliferation compared to the control at the corresponding time points. Taken together, these results suggest that running exercise might alleviate the mechanical allodynia induced by intradiscal CFA injection via disc repair and cell proliferation, which provides new evidence for future clinical use. PMID:25607736

Prevalence of Age-Related Changes in Ovine Lumbar Intervertebral Discs during Computed Tomography and Magnetic Resonance Imaging

PubMed Central

Nisolle, Jean-François; Bihin, Benoît; Kirschvink, Nathalie; Neveu, Fabienne; Clegg, Peter; Dugdale, Alexandra; Wang, Xiaoqing; Vandeweerd, Jean-Michel

2016-01-01

Ovine models are used to study intervertebral disc (IVD) degeneration. The objective of the current study was to assess the naturally occurring age-related changes of the IVD that can be diagnosed by CT and MRI in the lumbar spine of sheep. We used CT and T2-weighted MR images to score the IVD (L6S1 to L1L2) in 41 sheep (age, 6 mo to 11 y) that were euthanized for reasons not related to musculoskeletal disease. T2 mapping and measurement of T2 time of L6S1 to L2L3 were performed in 22 of the sheep. Degenerative changes manifested as early as 2 y of age and occurred at every IVD level. Discs were more severely damaged in older sheep. The age effect of the L6S1 IVD was larger than the average age effect for the other IVD. The current study provides evidence that lesions similar to those encountered in humans can be identified by CT and MRI in lumbar spine of sheep. Ideally, research animals should be assessed at the initiation of preclinical trials to determine the extent of prevalent degenerative changes. The ovine lumbosacral disc seems particularly prone to degeneration and might be a favorable anatomic site for studying IVD degeneration. PMID:27538861

Substance P stimulates production of inflammatory cytokines in human disc cells.

PubMed

Kepler, Christopher K; Markova, Dessislava Z; Hilibrand, Alan S; Vaccaro, Alexander R; Risbud, Makarand V; Albert, Todd J; Anderson, D Greg

2013-10-01

Laboratory study. The aims of this study were as follows: (1) to confirm that Substance P (SP) is expressed by nucleus pulposus (NP) and annulus fibrosus (AF) cells; (2) to determine the effect of SP on expression of inflammatory mediators in human disc cells and the effect of inflammatory mediators on the expression of SP; and (3) to characterize the relative expression of SP receptor isoforms in disc tissue and describe whether exposure to SP changes receptor expression. SP, classically described as a neurotransmitter, acts as an inflammatory regulator in other tissue types, but its role within the intervertebral disc has not been characterized. Human AF and NP cells from 7 individuals were expanded in monolayer and maintained in alginate bead culture. Cells were treated with SP or interleukin (IL)-1β/tumor necrosis factor-α (TNF-α). After treatment, the cells were recovered and then RNA was isolated and transcribed into cDNA. Quantitative reverse-transcriptase polymerase chain reaction was performed to evaluate expression of inflammatory mediators and SP and its receptors. Disc cells treated with SP demonstrated significant upregulation of IL-1β, IL-6, and IL-8 in NP and AF cells whereas significant upregulation of RANTES and TNF occurred only in the AF cells. AF and NP cells expressed SP at low levels; expression did not change significantly with SP treatment but was significantly upregulated after treatment with IL-1β/TNF-α. Both SP receptor isoforms were expressed by NP and AF cells. SP upregulates inflammatory mediators in disc cells. SP and its receptors were expressed in both NP and AF cells, and expression did not change after treatment with SP but increased after treatment with IL-1β/TNF-α. SP likely acts in an autocrine or paracrine manner in intervertebral disc cells and may be involved in "crosstalk" between disc cells and neurons, providing a potential mechanism for transmission of painful discogenic stimuli.

The role of interleukin-1 in the pathogenesis of human Intervertebral disc degeneration

PubMed Central

Le Maitre, Christine Lyn; Freemont, Anthony J; Hoyland, Judith Alison

2005-01-01

In this study, we investigated the hypotheses that in human intervertebral disc (IVD) degeneration there is local production of the cytokine IL-1, and that this locally produced cytokine can induce the cellular and matrix changes of IVD degeneration. Immunohistochemistry was used to localize five members of the IL-1 family (IL-1α, IL-1β, IL-1Ra (IL-1 receptor antagonist), IL-1RI (IL-1 receptor, type I), and ICE (IL-1β-converting enzyme)) in non-degenerate and degenerate human IVDs. In addition, cells derived from non-degenerate and degenerate human IVDs were challenged with IL-1 agonists and the response was investigated using real-time PCR for a number of matrix-degrading enzymes, matrix proteins, and members of the IL-1 family. This study has shown that native disc cells from non-degenerate and degenerate discs produced the IL-1 agonists, antagonist, the active receptor, and IL-1β-converting enzyme. In addition, immunopositivity for these proteins, with the exception of IL-1Ra, increased with severity of degeneration. We have also shown that IL-1 treatment of human IVD cells resulted in increased gene expression for the matrix-degrading enzymes (MMP 3 (matrix metalloproteinase 3), MMP 13 (matrix metalloproteinase 13), and ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs)) and a decrease in the gene expression for matrix genes (aggrecan, collagen II, collagen I, and SOX6). In conclusion we have shown that IL-1 is produced in the degenerate IVD. It is synthesized by native disc cells, and treatment of human disc cells with IL-1 induces an imbalance between catabolic and anabolic events, responses that represent the changes seen during disc degeneration. Therefore, inhibiting IL-1 could be an important therapeutic target for preventing and reversing disc degeneration. PMID:15987475

Is the rate of re-operation after primary lumbar microdiscectomy affected by surgeon grade or intra-operative lavage of the disc space?

PubMed

Ellenbogen, Jonathan R; Marlow, William; Fischer, Benjamin E; Tsegaye, Magnum; Wilby, Martin J

2014-04-01

STUDY DESIGN. Retrospective audit of consecutive patients. OBJECTIve. To investigate the re-operation rate following elective primary lumbar microdiscectomy and to determine whether principal surgeon grade and/or disc space lavage is a factor in recurrence. SUMMARY OF BACKGROUND DATA. Recurrent herniation of disc material following lumbar microdiscecomy surgery is one of the commonest complications of the procedure. Any reduction in the number of revision microdiscectomies performed per year would have a significant impact on patients' lives and on the health service economy. We undertook this study to ascertain whether principal surgeon grade and/or disc space lavage has an impact in reducing the re-operation rate. METHODS. We undertook a retrospective audit of patients who underwent elective primary lumbar microdiscectomy, over a 3-year period (n = 971). RESULTS. The overall re-operation rate for primary elective microdiscectomy was 3.8%, consistent with the published literature. The relative risk of re-operation in patients primarily operated by registrar surgeons was 1.2 fold the risk in patients operated by consultants (95% CI: 0.62, 2.35) although not statistically significant (p = 0.568). The risk of re-operation in the 'non lavage' group was 2.15 times the risk in the 'lavage' group (95% CI: 0.63, 7.34), but it did not reach significance (p = 0.222). CONCLUSIONS. Principal surgeon grade and intervertebral disc lavage have not been found conclusively to be factors in the rate of recurrence. This information is useful to reassure patients that their outcome from such surgery is not dependent on the grade of surgeon performing the operation. There is a possible trend towards intervertebral disc lavage reducing the rate of recurrence.

Catabolic effects of endothelial cell-derived microparticles on disc cells: Implications in intervertebral disc neovascularization and degeneration.

PubMed

Pohl, Pedro H I; Lozito, Thomas P; Cuperman, Thais; Yurube, Takashi; Moon, Hong J; Ngo, Kevin; Tuan, Rocky S; St Croix, Claudette; Sowa, Gwendolyn A; Rodrigues, Luciano M R; Kang, James D; Vo, Nam V

2016-08-01

Neovascularization of intervertebral discs, a phenomenon considered pathological since normal discs are primarily avascular structures, occurs most frequently in annulus fibrosus (AF) of degenerated discs. Endothelial cells (ECs) are involved in this process, but the mechanism of the interaction between AF and endothelial cells is unclear. In this study, we evaluated the effects on matrix catabolic activity of AF cells by the extracellular endothelial microparticles (EMPs) and soluble protein factors (SUP fraction) produced from ECs. Passage 1 human AF cells grown in monolayer cultures were treated for 72 h with 250 µg of EMPs or SUP fraction isolated from culture of the microvascular endothelial cell line, HEMC-I. Live-cell imaging revealed uptake of EMPs by AF cells. RT-PCR analysis demonstrated increased mRNA expression of MMP-1 (50.3-fold), MMP-3 (4.5-fold) and MMP-13 (5.5-fold) in AF cell cultures treated with EMPs compared to untreated control. Western analysis also demonstrated increased MMP protein expression in EMP-treated AF cells. AF cells treated with the SUP fraction also exhibited a dramatic increase in MMP mRNA and protein expression. Increased MMP expression is primarily due to EMP or SUP stimulation of AF cells since EMPs or SUP fraction alone contained negligible amount of MMPs. Interestingly, MMP activity was elevated in AF cell cultures treated with EMPs but not with SUP. This study revealed enhanced matrix catabolism as a molecular consequence of action of ECs on AF cells via EMPs, which might be expected during neo-angiogenesis of degenerating disc. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1466-1474, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

[Biomechanics changes of lumbar spine caused by foraminotomy via percutaneous transforaminal endoscopic lumbar discectomy].

PubMed

Qian, J; Yu, S S; Liu, J J; Chen, L; Jing, J H

2018-04-03

Objective: To analyze the biomechanics changes of lumbar spine caused by foraminotomy via percutaneous transforaminal endoscopic lumbar discectomy using the finite element method. Methods: Three healthy adult males (aged 35.6 to 42.3 years) without spinal diseases were enrolled in this study and 3D-CT scans were carried out to obtain the parameters of lumbar spine. Mimics software was applied to build a 3D finite element model of lumbar spine. Graded resections (1/4, 2/4, 3/4 and 4/4) of the left superior articular process of L(5) were done via percutaneous transforaminal endoscopic lumbar discectomy. Then, the pressure of the L(4/5) right facets, the pressure of the L(4/5) intervertebral disc and the motion of lumbar spine were recorded after simulating the normal flexion and extension, lateral flexion and rotation of the lumbar spine model during different resections. The data were compared among groups with analysis of variance. Results: Comparing with the normal group, after 1/4 resection of the left superior articular process of L(5), the pressure of the L(4/5) right facets showed significant differences during left lateral flexion and rotation of lumbar spine ( q =8.823, 8.248, both P <0.05); and the pressure of L(4/5) intervertebral disc also changed significantly during extension and right rotation of lumbar spine ( q =6.918, 6.438, both P <0.05); the motion of lumbar spine showed obvious differences during right lateral flexion and rotation ( q =6.845, 7.772, 13.58, all P <0.05). Comparing with the normal group, after 2/4 resection of the left superior articular process of L(5), the pressure of the L(4/5) right facets presented significant differences during all conditions ( q =5.670-17.830, all P <0.05); the pressure of L(4/5) intervertebral disc changed significantly during flexion, extension, lateral flexion and right rotation ( q =5.260, 17.150, 5.727, 8.890, 15.660, all P <0.05); the motion of lumbar spine also existed differences during extension, lateral flexion and rotation ( q =9.106, 5.431, 12.060, 11.160, 17.260, all P <0.05). However, after 3/4 resections, the pressure of the L(4/5) right facets, the pressure of the L(4/5) intervertebral disc and the motion of lumbar spine presented differences during all conditions when compared with those in normal group ( q =6.303-25.48, all P <0.05). After 4/4 resections, the pressure of the L(4/5) right facets and the pressure of the L(4/5) intervertebral disc and the motion of lumbar spine showed significant differences during all conditions when compared with those in normal group ( q =8.065-45.70, all P <0.05). Conclusions: The biomechanics and the stability of lumbar spine changed partly after 1/4 resection of the superior articular process and obviously after more than 2/4 is resected. The superior articular process should be paid more attention during foraminotomy via percutaneous transforaminal endoscopic lumbar discectomy.

The spectrum of neurological disorders presenting at a neurology clinic in Yaoundé, Cameroon.

PubMed

Tegueu, Callixte Kuate; Nguefack, Séraphin; Doumbe, Jacques; Fogang, Yannick Fogoum; Mbonda, Paul Chimi; Mbonda, Elie

2013-01-01

The burden of these neurological diseases is higher in developing countries. However, there is a paucity and scarcity of literature on neurological diseases in sub-Saharan Africa. This study was therefore undertaken to determine the pattern of neurological diseases in this setting and then, compare to those elsewhere in the African continent and also serve as a baseline for planning and care for neurological disorders in Cameroon. The study was conducted at the Clinique Bastos, in Yaoundé, city capital of Cameroon, centre region. Over a period of six years, all medical records were reviewed by a neurologist and neurological diagnoses classified according to ICD-10. Out of 4526 admissions 912 patients (20.15%) were given a neurological diagnosis. The most frequent neurological disorders were headache (31.9%), epilepsy (9.86%), intervertebral disc disorder (7.67%), followed by lumbar and cervical arthrosis, polyneuropathy, stroke, Parkinson disease and dementia. According to ICD-10 classification, Episodic and paroxysmal disorders (headaches, epilepsy, cerebrovascular, sleep disorders) were observed on 424 (46.48%) patients; followed by nerve, nerve root and plexus disorders in 115 (12.6%) patients. The above data emphasizes that neurological disease contributes substantially to morbidity in an urban African hospital. Headaches, epilepsy and intervertebral disc disorders are major causes of morbidity.

In-situ photopolymerized and monitored implants: successful application to an intervertebral disc replacement

NASA Astrophysics Data System (ADS)

Schmocker, Andreas M.; Khoushabi, Azadeh; Bourban, Pierre-Etienne; Schizas, Constantin; Pioletti, Dominique; Moser, Christophe

2016-02-01

Photopolymerization is a common method to harden materials initially in a liquid state. A surgeon can directly trigger the solidification of a dental implant or a bone or tissue filler by using ultra-violet light. Traditionally, photopolymerization has been used mainly in dentistry. Over the last decade advances in material development including a wide range of biocompatible gel- and cement-systems open up a new avenue for in-situ photopolymerization. We designed a miniaturized light probe where a photoactive material can be 1) mixed, pressurized and injected 2) photopolymerized or photoactivated and 3) monitored during the chemical reaction. The device enables surgeries to be conducted through a hole smaller than 500 μm in diameter. Using a combination of Raman and fluorescence spectroscopy, the current state of the photopolymerization was inferred and monitored in real time within an in-vitro tissue model. It was also possible to determine roughly the position of the probe within the tissue cavity by analysing the fluorescence signal. Using the technique hydrogels were successfully implanted into a bovine intervertebral disc model. Mechanical tests could not obstruct the functionality of the implant. Finally, the device was also used for other application such as the implantation of a hydrogel into an aneurysm tissue cavity which will be presented at the conference.

Diagnosis of unstable cervical spine injuries: laboratory support for the use of axial traction to diagnose cervical spine instability.

PubMed

Kalantar, Babak S; Hipp, John A; Reitman, Charles A; Dreiangel, Niv; Ben-Galim, Peleg

2010-10-01

The ability to detect damage to the intervertebral structures is critical in the management of patients after blunt trauma. A practical and inexpensive method to identify severe structural damage not clearly seen on computed tomography would be of benefit. The objective of this study was to assess whether ligamentous injury in the subaxial cervical spine can be reliably detected by analysis of lateral radiographs taken with and without axial traction. Twelve fresh, whole, postrigor-mortis cadavers were used for this study. Lateral cervical spine radiographs were obtained during the application of 0 N, 89 N, and 178 N of axial traction applied to the head. Progressive incremental sectioning of posterior structures was then performed at C4-C5 with traction imaging repeated after each intervention. Intervertebral distraction was analyzed using computer-assisted software. Almost imperceptible intervertebral separation was found when traction was applied to intact spines. In the subaxial cervical spine, the average posterior disc height consistently increased under traction in severely injured spines. The average disc height increase was 14% of the C4 upper endplate width, compared with an average of 2% in the noninjured spines. A change of more than 5% in posterior disc height under traction was above the 95% confidence interval for intact spines, with sensitivity of 83% and specificity of 80%. Applied force of 89 N (20 lb) was sufficient to demonstrate injury. The combination of assessing alignment and distraction under traction increased both the sensitivity and specificity to nearly 100%. This study supports further clinical investigations to determine whether low-level axial traction may be a useful adjunct for detecting unstable subaxial cervical spine injuries in an acute setting.

Granulocytic sarcoma: a rare cause of sciatica.

PubMed

Valsamis, Epaminondas Markos; Glover, Thomas Edward

2017-02-15

We describe a case report of a man aged 56 years with a 4-month history of right-sided sciatica-type pain with subclinical disc prolapse evident on MRI. Worsening pain together with the appearance of a tender mass in his right buttock prompted further imaging, which demonstrated an infiltrative mass engulfing the lumbosacral plexus. This was later shown to be a granulocytic sarcoma on biopsy. Intervertebral disc herniation can be an incidental finding and is not always the cause of sciatica. 2017 BMJ Publishing Group Ltd.

A systematic review of the passive straight leg raising test as a diagnostic aid for low back pain (1989 to 2000).

PubMed

Rebain, Richard; Baxter, G David; McDonough, Suzanne

2002-09-01

A systematic review. This systematic review sought papers (January 1989-January 2000) on the passive straight leg raising test (PSLR) as a diagnostic component for low back pain (LBP) to identify, summarize, and assess developments in the test procedure, the factors influencing PSLR outcome, and the clinical significance of that outcome. Previous studies suggested that the PSLR tractioned the sciatic nerve and that diminished leg elevation with reproduced pain indicated low lumbar intervertebral disc pathology. Searches on six computerized bibliographic databases identified publications written about the PSLR. Papers were excluded if they were published before January 1989, were non-English language papers, or employed either an active SLR or a PSLR for purposes other than LBP diagnosis. The references of qualifying papers (and the references of references) were searched. Contact with primary authors, and others known to be active in this field, was attempted. The PSLR procedure remains unchanged. The influence of hip rotation during the PSLR was discussed without consensus. Biomechanical devices improved intra- and interobserver reliability and so increased test reproducibility. Hamstrings were found to have a defensive role in protecting nerve roots by limiting PSLR range in cases of nerve root inflammation. A small diurnal variation in the PSLR may imply a poorer prognosis. A positive PSLR at 4 months after lumbar intervertebral disc surgery predicted poor reoperative outcome, and a negative 4-month PSLR predicted excellent outcome. The influence of psychosocial factors was not discussed, neither was the diagnostic significance of a negative PSLR outcome. There remains no standard PSLR procedure, no consensus on interpretation of results, and little recognition that a negative PSLR test outcome may be of greater diagnostic value than a positive one. The causal link between LBP pathology and hamstring action remains unclear. There is a need for research into the clinical use of the PSLR; its intra- and interobserver reliability; the influences of age, gender, diurnal variation, and psychosocial factors; and its predictive value in lumbar intervertebral disc surgery.

Anti-inflammatory Chitosan/Poly-γ-glutamic acid nanoparticles control inflammation while remodeling extracellular matrix in degenerated intervertebral disc.

PubMed

Teixeira, Graciosa Q; Leite Pereira, Catarina; Castro, Flávia; Ferreira, Joana R; Gomez-Lazaro, Maria; Aguiar, Paulo; Barbosa, Mário A; Neidlinger-Wilke, Cornelia; Goncalves, Raquel M

2016-09-15

Intervertebral disc (IVD) degeneration is one of the most common causes of low back pain (LBP), the leading disorder in terms of years lived with disability. Inflammation can play a role in LPB, while impairs IVD regeneration. In spite of this, different inflammatory targets have been purposed in the context of IVD regeneration. Anti-inflammatory nanoparticles (NPs) of Chitosan and Poly-(γ-glutamic acid) with a non-steroidal anti-inflammatory drug, diclofenac (Df), were previously shown to counteract a pro-inflammatory response of human macrophages. Here, the effect of intradiscal injection of Df-NPs in degenerated IVD was evaluated. For that, Df-NPs were injected in a bovine IVD organ culture in pro-inflammatory/degenerative conditions, upon stimulation with needle-puncture and interleukin (IL)-1β. Df-NPs were internalized by IVD cells, down-regulating IL-6, IL-8, MMP1 and MMP3, and decreasing PGE2 production, compared with IL-1β-stimulated IVD punches. Interestingly, at the same time, Df-NPs promoted an up-regulation of extracellular matrix (ECM) proteins, namely collagen type II and aggrecan. Allover, this study suggests that IVD treatment with Df-NPs not only reduces inflammation, but also delays and/or decreases ECM degradation, opening perspectives to new intradiscal therapies for IVD degeneration, based on the modulation of inflammation. Degeneration of the IVD is an age-related progressive process considered to be the major cause of spine disorders. The pro-inflammatory environment and biomechanics of the degenerated IVD is a challenge for regenerative therapies. The novelty of this work is the intradiscal injection of an anti-inflammatory therapy based on Chitosan (Ch)/Poly-(γ-glutamic acid) (γ-PGA) nanoparticles (NPs) with an anti-inflammatory drug (diclofenac, Df), previously developed by us. This drug delivery system was tested in a pro-inflammatory/degenerative intervertebral disc ex vivo model. The main findings support the success of an anti-inflammatory therapy for degenerated IVD that not only reduces inflammation but also promotes native IVD matrix production. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Laser-induced activation of regeneration processes in spine disc cartilage

NASA Astrophysics Data System (ADS)

Sobol, Emil N.; Vorobjeva, Natalia N.; Sviridov, Alexander P.; Omelchenko, Alexander I.; Baskov, Andrey V.; Shekhter, Anatoliy B.; Baskov, Vladimir A.; Feldchtein, Felix I.; Kamensky, Vladislav A.; Kuranov, Roman V.

2000-05-01

The effect of laser radiation on the regeneration processes in spine disk cartilage has been studied in-vivo. We used rabbits as a model and a Holmium (2.09 micrometer) and an Erbium fiber (1.56 micrometer) lasers for irradiation the discs which were preliminary opened to remove annulus fibrosus and the nucleus pulposus of the intervertebral disc. The irradiated zone has been examined using an optical coherent tomography in one month after the operation and conventional histological technique in two months after the laser operation. It has been shown that laser radiation promotes the growth of the new cartilaginous tissue of fibrous and hyaline types.

Patterns of diagnostic care in nonspecific low back pain: Relation to patient satisfaction and perceived health

DTIC Science & Technology

2006-12-19

Spondylosis and other allied disorders 722 Intervertebral disc disorders 723* Other disorders of cervical region 724 Other and...Osteoporosis 733.13* Pathologic fracture 846 Sprains & strains of sacroiliac region 847.1 Thoracic sprain 847.2 Lumbar sprain

Assessment and rehabilitation of chronic low back pain in baseball: part II

PubMed Central

Wasser, Joseph G.; Zaremski, Jason L.; Herman, Daniel C.; Vincent, Heather K.

2017-01-01

Repetitive throwing and hitting motions in baseball place mechanical stresses to the lumbar spine which may cause low back pain (LBP). Pain may be due to vertebral stress reactions or insufficiency fractures, intervertebral disc degeneration or intervertebral disc herniation. Untreated chronic conditions have high potential to lead to a more significant injury such as spondylolysis. Chronic LBP increases the risk for missed playing time, early career termination and lower quality of life after retirement. Proper clinical assessment and prevention/rehabilitation of LBP in this population is thus important for performance, play time and overall long-term quality of life. This narrative review synopsizes the available evidence for assessment and rehabilitation of baseball players with LBP, including the structured rehabilitative techniques and programmes which should be administered to affected players. The state of the evidence suggests that there are deficits in identifying the optimal prevention and rehabilitation prescription components for the variety of LBP-inducing injuries in this athletic population. PMID:28128000

Assessment and rehabilitation of chronic low back pain in baseball: part II.

PubMed

Wasser, Joseph G; Zaremski, Jason L; Herman, Daniel C; Vincent, Heather K

2017-01-01

Repetitive throwing and hitting motions in baseball place mechanical stresses to the lumbar spine which may cause low back pain (LBP). Pain may be due to vertebral stress reactions or insufficiency fractures, intervertebral disc degeneration or intervertebral disc herniation. Untreated chronic conditions have high potential to lead to a more significant injury such as spondylolysis. Chronic LBP increases the risk for missed playing time, early career termination and lower quality of life after retirement. Proper clinical assessment and prevention/rehabilitation of LBP in this population is thus important for performance, play time and overall long-term quality of life. This narrative review synopsizes the available evidence for assessment and rehabilitation of baseball players with LBP, including the structured rehabilitative techniques and programmes which should be administered to affected players. The state of the evidence suggests that there are deficits in identifying the optimal prevention and rehabilitation prescription components for the variety of LBP-inducing injuries in this athletic population.

Urinary 3-hydroxypropyl mercapturic acid (3-HPMA) concentrations in dogs with acute spinal cord injury due to intervertebral disc herniation.

PubMed

Sangster, A M; Zheng, L; Bentley, R T; Shi, R; Packer, R A

2017-01-01

The aim of this study was to investigate urinary 3-hydroxypropyl mercapturic acid (3-HPMA), a metabolite of acrolein, as a novel biomarker in acute spinal cord injury (ASCI) due to intervertebral disc herniation in dogs. Urine from 10 client-owned dogs with ASCI collected at presentation and 10 control dogs was analyzed for 3-HPMA. The median urinary 3-HPMA concentration in ASCI dogs was significantly higher than in control dogs, but was not correlated with the severity of ASCI. The median urinary 3-HPMA concentration in intact dogs was higher than in neutered dogs. Higher urinary 3-HPMA concentrations in dogs after ASCI support a role for acrolein, a cytotoxic by-product of lipid peroxidation, in canine ASCI. Urinary 3-HPMA could be used as a biomarker in future clinical trials to measure the effect of therapeutic intervention of reducing acrolein after ASCI. Copyright © 2016. Published by Elsevier Ltd.

The natural history and risk factors of musculoskeletal conditions resulting in disability among US Army personnel

PubMed Central

Lincoln, Andrew E.; Smith, Gordon S.; Amoroso, Paul J.; Bell, Nicole S.

2007-01-01

We describe the natural history of 13 musculoskeletal conditions requiring hospitalization and identify demographic, behavioral, psychosocial, occupational, and clinical characteristics most strongly associated with disability discharge from the Army. Subjects included 15,268 active-duty personnel hospitalized for a common musculoskeletal condition between the years 1989–1996 who were retrospectively followed through 1997. Back conditions had the greatest 5-year cumulative risk of disability (21%, 19%, and 17% for intervertebral disc displacement, intervertebral disc degeneration, and nonspecific low back pain, respectively). Cox proportional hazards models identified the following risk factors for disability among males: lower pay grade, musculoskeletal diagnosis, shorter length of service, older age, occupational category, lower job satisfaction, recurrent musculoskeletal hospitalizations, more cigarette smoking, greater work stress, and heavier physical demands. Among females, fewer covariates reached statistical significance, although lower education level was significant in more than one model. Modifiable risk factors related to work (job satisfaction, work stress, physical demands, occupation) and health behaviors (smoking) suggest possible targets for intervention. PMID:12441574

Comparison of B0 versus B0 and B1 field inhomogeneity correction for glycosaminoglycan chemical exchange saturation transfer imaging.

PubMed

Müller-Lutz, Anja; Ljimani, Alexandra; Stabinska, Julia; Zaiss, Moritz; Boos, Johannes; Wittsack, Hans-Jörg; Schleich, Christoph

2018-05-14

The study compares glycosaminoglycan chemical exchange saturation transfer (gagCEST) imaging of intervertebral discs corrected for solely B 0 inhomogeneities or both B 0 and B 1 inhomogeneities. Lumbar intervertebral discs of 20 volunteers were examined with T 2 -weighted and gagCEST imaging. Field inhomogeneity correction was performed with B 0 correction only and with correction of both B 0 and B 1 . GagCEST effects measured by the asymmetric magnetization transfer ratio (MTR asym ) and signal-to-noise ratio (SNR) were compared between both methods. Significant higher MTR asym and SNR values were obtained in the nucleus pulposus using B 0 and B 1 correction compared with B 0 -corrected gagCEST. The GagCEST effect was significantly different in the nucleus pulposus compared with the annulus fibrosus for both methods. The B 0 and B 1 field inhomogeneity correction method leads to an improved quality of gagCEST imaging in IVDs compared with only B 0 correction.

Dysuria due to discospondylitis and intervertebral disc herniation in a male alpaca (Vicugna pacos).

PubMed

Sickinger, Marlene; Hirz, Manuela; Schmidt, Martin J; Reinacher, Manfred

2016-05-31

Dysuria in camelids is usually associated with the presence of lower urinary tract disease such as urolithiasis. As another differential diagnosis, urine retention may be caused by neurological disturbances resulting from infections of the spinal cord, discospondylitis or trauma. A 2.5-year-old male Huacaya alpaca (Vicugna pacos) presented with dysuria due to damage of the lumbosacral intumescence of the spinal cord. On presentation the alpaca was recumbent. Clinical examination revealed abdominal pain, oliguria, leucopenia with neutrophilia, and slightly elevated creatinine kinase. Ultrasonography of the abdomen showed an irregularly shaped, dilated urinary bladder with hyperechoic serosa. Magnetic resonance imaging revealed discospondylitis of the fourth and fifth lumbar vertebrae and herniation of the intervertebral disc between these vertebrae and the spinal cord. Postmortem examination confirmed severe chronic purulent discospondylitis with ventral spondylosis and narrowing of the spinal canal. Urolithiasis could not be verified. Although rare, diseases of the spinal cord should be considered as a differential diagnosis for impaired micturition in camelids.

Does T2 mapping of the posterior annulus fibrosus indicate the presence of lumbar intervertebral disc herniation? A 3.0 Tesla magnetic resonance study.

PubMed

Messner, Alina; Stelzeneder, David; Trattnig, Stefan; Welsch, Götz H; Schinhan, Martina; Apprich, Sebastian; Brix, Martin; Windhager, Reinhard; Trattnig, Siegfried

2017-03-01

Indicating lumbar disc herniation via magnetic resonance imaging (MRI) T2 mapping in the posterior annulus fibrosus (AF). Sagittal T2 maps of 313 lumbar discs of 64 patients with low back pain were acquired at 3.0 Tesla (3T). The discs were rated according to disc herniation and bulging. Region of interest (ROI) analysis was performed on median, sagittal T2 maps. T2 values of the AF, in the most posterior 10% (PAF-10) and 20% of the disc (PAF-20), were compared. A significant increase in the T2 values of discs with herniations affecting the imaged area, compared to bulging discs and discs with lateral herniation, was shown in the PAF-10, where no association to the NP was apparent. The PAF-20 exhibited a moderate correlation to the nucleus pulposus (NP). High T2 values in the PAF-10 suggest the presence of disc herniation (DH). The results indicate that T2 values in the PAF-20 correspond more to changes in the NP.

Progression, incidence, and risk factors for intervertebral disc degeneration in a longitudinal population-based cohort: the Wakayama Spine Study.

PubMed

Teraguchi, M; Yoshimura, N; Hashizume, H; Yamada, H; Oka, H; Minamide, A; Nagata, K; Ishimoto, Y; Kagotani, R; Kawaguchi, H; Tanaka, S; Akune, T; Nakamura, K; Muraki, S; Yoshida, M

2017-07-01

The present study examined the progression, incidence, and risk factors for intervertebral disc degeneration (DD) throughout the lumbar spine using magnetic resonance imaging (MRI) in a large population-based cohort. We followed up 617 subjects for more than 4 years as part of the Wakayama Spine Study. 1) "Progression of DD" in each of the entire, upper (L1/2 to L3/4) and lower (L4/5 and L5/S1) lumbar spine was defined as Pfirrmann grade progression at follow-up in at least one disc in the affected region. 2) "Incidence of DD" in each of these regions was defined if all discs were grade 3 or lower (white disc) at baseline, and at least one disc had progressed to grade 4 or higher (black disc) at follow-up. Logistic regression analyses were used to determine the risk factors for progression and incidence of DD. DD progression and incidence in the entire lumbar spine were 52.0% and 31.6% in men, and 60.4% and 44.7% in women, respectively. Women was associated with DD progression in the upper lumbar spine (odds ratio [OR] = 1.68, 95% confidence interval [CI] = 1.18-2.42). Aging was associated with the incidence of DD in each region (entire: OR = 1.14, CI = 1.06-1.14; upper: OR = 1.10, CI = 1.05-1.15; lower: OR = 1.11, CI = 1.05-1.19). Diabetes mellitus (DM) was associated with the incidence of DD in the upper lumbar spine (OR = 6.83, CI = 1.07-133.7). This 4-year longitudinal study is the first to demonstrate DD progression and incidence in the lumbar spine and their risk factors in a large population-based cohort. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

38 CFR Appendix B to Part 4 - Numerical Index of Disabilities

Code of Federal Regulations, 2011 CFR

2011-07-01

... Diagnostic Code No. THE MUSCULOSKELETAL SYSTEM Acute, Subacute, or Chronic Diseases 5000 Osteomyelitis, acute... Intervertebral disc syndrome. Hip and Thigh 5250 Hip, ankylosis. 5251 Thigh, limitation of extension. 5252 Thigh.... 6204 Peripheral vestibular disorders. 6205 Meniere's syndrome. 6207 Loss of auricle. 6208 Malignant...

38 CFR Appendix B to Part 4 - Numerical Index of Disabilities

Code of Federal Regulations, 2010 CFR

2010-07-01

... Diagnostic Code No. THE MUSCULOSKELETAL SYSTEM Acute, Subacute, or Chronic Diseases 5000 Osteomyelitis, acute... Intervertebral disc syndrome. Hip and Thigh 5250 Hip, ankylosis. 5251 Thigh, limitation of extension. 5252 Thigh.... 6204 Peripheral vestibular disorders. 6205 Meniere's syndrome. 6207 Loss of auricle. 6208 Malignant...

38 CFR Appendix B to Part 4 - Numerical Index of Disabilities

Code of Federal Regulations, 2012 CFR

2012-07-01

... Diagnostic Code No. THE MUSCULOSKELETAL SYSTEM Acute, Subacute, or Chronic Diseases 5000 Osteomyelitis, acute... Intervertebral disc syndrome. Hip and Thigh 5250 Hip, ankylosis. 5251 Thigh, limitation of extension. 5252 Thigh.... 6204 Peripheral vestibular disorders. 6205 Meniere's syndrome. 6207 Loss of auricle. 6208 Malignant...

38 CFR Appendix B to Part 4 - Numerical Index of Disabilities

Code of Federal Regulations, 2014 CFR

2014-07-01

... Diagnostic Code No. THE MUSCULOSKELETAL SYSTEM Acute, Subacute, or Chronic Diseases 5000 Osteomyelitis, acute... Intervertebral disc syndrome. Hip and Thigh 5250 Hip, ankylosis. 5251 Thigh, limitation of extension. 5252 Thigh.... 6204 Peripheral vestibular disorders. 6205 Meniere's syndrome. 6207 Loss of auricle. 6208 Malignant...

38 CFR Appendix B to Part 4 - Numerical Index of Disabilities

Code of Federal Regulations, 2013 CFR

2013-07-01

... Diagnostic Code No. THE MUSCULOSKELETAL SYSTEM Acute, Subacute, or Chronic Diseases 5000 Osteomyelitis, acute... Intervertebral disc syndrome. Hip and Thigh 5250 Hip, ankylosis. 5251 Thigh, limitation of extension. 5252 Thigh.... 6204 Peripheral vestibular disorders. 6205 Meniere's syndrome. 6207 Loss of auricle. 6208 Malignant...

Neurological complications of lumbar artificial disc replacement and comparison of clinical results with those related to lumbar arthrodesis in the literature: results of a multicenter, prospective, randomized investigational device exemption study of Charité intervertebral disc. Invited submission from the Joint Section Meeting on Disorders of the Spine and Peripheral Nerves, March 2004.

PubMed

Geisler, Fred H; Blumenthal, Scott L; Guyer, Richard D; McAfee, Paul C; Regan, John J; Johnson, J Patrick; Mullin, Bradford

2004-09-01

Arthrodesis is the gold standard for surgical treatment of lumbar degenerative disc disease (DDD). Solid fusion, however, can cause stress and increased motion in the segments adjacent to the fused level. This may initiate and/or accelerate the adjacent-segment disease process. Artificial discs are designed to restore and maintain normal motion of the lumbar intervertebral segment. Restoring and maintaining normal motion of the segment reduces stresses and loads on adjacent level segments. A US Food and Drug Administration Investigational Device Exemptions multicentered study of the Charité artificial disc was completed. The control group consisted of individuals who underwent anterior lumbar interbody fusion involving BAK cages and iliac crest bone graft. This is the first report of Class I data in which a lumbar artificial disc is compared with lumbar fusion. Of 304 individuals enrolled in the study, 205 were randomized to the Charité disc-treated group and 99 to the BAK fusion-treated (control) group. Neurological status was equivalent between the two groups at 6, 12, and 24 months postoperatively. The number of patients with major, minor, or other neurological complications was equivalent. There was a greater incidence of both major and minor complications in the BAK fusion group at 0 to 42 days postoperatively. Compared with data reported in the lumbar fusion literature, the Charité disc-treated patients had equivalent or better mean changes in visual analog scale and Oswestry Disability Index scores. The Charité artificial disc is safe and effective for the treatment of single-level lumbar DDD, resulting in no higher incidence of neurological complications compared with BAK-assisted fusion and leading to equivalent or better outcomes compared with those obtained in the control group and those reported in the lumbar fusion literature.

Fungal discitis due to Aspergillus terreus in a patient with acute lymphoblastic leukemia.

PubMed Central

Park, K. U.; Lee, H. S.; Kim, C. J.; Kim, E. C.

2000-01-01

We report a case of Aspergillus terreus discitis which developed in a patient with acute lymphoblastic leukemia following induction chemotherapy. A. terreus was isolated from sputum, one month earlier, but the physician did not consider it significant at the time. Magnetic resonance imaging study showed the involvement of L3-4, L4-5 and L5-S1 intervertebral discs. Etiology was established by means of histology and culturing a surgical specimen of disc materials. Our patient survived after a surgical debridement and amphotericin B administration with a total dose of 2.0 g. Discitis caused by Aspergillus terreus is a very rare event. A. terreus is one of the invasive Aspergillus species. The pathogenetic mechanism is discussed and the literature is reviewed. PMID:11194199

Fungal discitis due to Aspergillus terreus in a patient with acute lymphoblastic leukemia.

PubMed

Park, K U; Lee, H S; Kim, C J; Kim, E C

2000-12-01

We report a case of Aspergillus terreus discitis which developed in a patient with acute lymphoblastic leukemia following induction chemotherapy. A. terreus was isolated from sputum, one month earlier, but the physician did not consider it significant at the time. Magnetic resonance imaging study showed the involvement of L3-4, L4-5 and L5-S1 intervertebral discs. Etiology was established by means of histology and culturing a surgical specimen of disc materials. Our patient survived after a surgical debridement and amphotericin B administration with a total dose of 2.0 g. Discitis caused by Aspergillus terreus is a very rare event. A. terreus is one of the invasive Aspergillus species. The pathogenetic mechanism is discussed and the literature is reviewed.

[Design and research progress of zero profile cervical Interbody cage].

PubMed

Zhu, Jia; Wang, Song; Liao, Zhenhua; Liu, Weiqiang

2017-02-01

Zero profile cervical interbody cage is an improvement of traditional fusion products and necessary supplement of emerging artificial intervertebral disc products. When applied in Anterior Cervical Decompression Fusion(ACDF), zero profile cervical interbody cage can preserve the advantages of traditional fusion and reduce the incidence of postoperative complications. Moreover, zero profile cervical interbody cage can be applied under the tabu symptoms of Artificial Cervical Disc Replacement(ACDR). This article summarizes zero profile interbody cage products that are commonly recognized and widely used in clinical practice in recent years, and reviews the progress of structure design and material research of zero profile cervical interbody cage products. Based on the latest clinical demands and research progress, this paper also discusses the future development directions of zero profile interbody cage.

Unique glycosignature for intervertebral disc and articular cartilage cells and tissues in immaturity and maturity.

PubMed

Collin, E C; Kilcoyne, M; White, S J; Grad, S; Alini, M; Joshi, L; Pandit, A S

2016-03-11

In this study, on/off markers for intervertebral disc (IVD) and articular cartilage (AC) cells (chondrocytes) and distinct glycoprofiles of cell and tissue-types were identified from immaturity to maturity. Three and eleven month-old ovine IVD and AC tissues were histochemically profiled with a panel of lectins and antibodies. Relationships between tissue and cell types were analysed by hierarchical clustering. Chondroitin sulfate (CS) composition of annulus fibrosus (AF), nucleus pulposus (NP) and AC tissues was determined by HPLC analysis. Clear on/off cell type markers were identified, which enabled the discrimination of chondrocytes, AF and NP cells. AF and NP cells were distinguishable using MAA, SNA-I, SBA and WFA lectins, which bound to both NP cells and chondrocytes but not AF cells. Chondrocytes were distinguished from NP and AF cells with a specific binding of LTA and PNA lectins to chondrocytes. Each tissue showed a unique CS composition with a distinct switch in sulfation pattern in AF and NP tissues upon disc maturity while cartilage maintained the same sulfation pattern over time. In conclusion, distinct glycoprofiles for cell and tissue-types across age groups were identified in addition to altered CS composition and sulfation patterns for tissue types upon maturity.

T1ρ magnetic resonance: basic physics principles and applications in knee and intervertebral disc imaging.

PubMed

Wáng, Yì-Xiáng J; Zhang, Qinwei; Li, Xiaojuan; Chen, Weitian; Ahuja, Anil; Yuan, Jing

2015-12-01

T1ρ relaxation time provides a new contrast mechanism that differs from T1- and T2-weighted contrast, and is useful to study low-frequency motional processes and chemical exchange in biological tissues. T1ρ imaging can be performed in the forms of T1ρ-weighted image, T1ρ mapping and T1ρ dispersion. T1ρ imaging, particularly at low spin-lock frequency, is sensitive to B0 and B1 inhomogeneity. Various composite spin-lock pulses have been proposed to alleviate the influence of field inhomogeneity so as to reduce the banding-like spin-lock artifacts. T1ρ imaging could be specific absorption rate (SAR) intensive and time consuming. Efforts to address these issues and speed-up data acquisition are being explored to facilitate wider clinical applications. This paper reviews the T1ρ imaging's basic physic principles, as well as its application for cartilage imaging and intervertebral disc imaging. Compared to more established T2 relaxation time, it has been shown that T1ρ provides more sensitive detection of proteoglycan (PG) loss at early stages of cartilage degeneration. T1ρ has also been shown to provide more sensitive evaluation of annulus fibrosis (AF) degeneration of the discs.

Localized strain measurements of the intervertebral disc annulus during biaxial tensile testing.

PubMed

Karakolis, Thomas; Callaghan, Jack P

2015-01-01

Both inter-lamellar and intra-lamellar failures of the annulus have been described as potential modes of disc herniation. Attempts to characterize initial lamellar failure of the annulus have involved tensile testing of small tissue samples. The purpose of this study was to evaluate a method of measuring local surface strains through image analysis of a tensile test conducted on an isolated sample of annular tissue in order to enhance future studies of intervertebral disc failure. An annulus tissue sample was biaxial strained to 10%. High-resolution images captured the tissue surface throughout testing. Three test conditions were evaluated: submerged, non-submerged and marker. Surface strains were calculated for the two non-marker conditions based on motion of virtual tracking points. Tracking algorithm parameters (grid resolution and template size) were varied to determine the effect on estimated strains. Accuracy of point tracking was assessed through a comparison of the non-marker conditions to a condition involving markers placed on tissue surface. Grid resolution had a larger effect on local strain than template size. Average local strain error ranged from 3% to 9.25% and 0.1% to 2.0%, for the non-submerged and submerged conditions, respectively. Local strain estimation has a relatively high potential for error. Submerging the tissue provided superior strain estimates.

T1ρ magnetic resonance: basic physics principles and applications in knee and intervertebral disc imaging

PubMed Central

Zhang, Qinwei; Li, Xiaojuan; Chen, Weitian; Ahuja, Anil; Yuan, Jing

2015-01-01

T1ρ relaxation time provides a new contrast mechanism that differs from T1- and T2-weighted contrast, and is useful to study low-frequency motional processes and chemical exchange in biological tissues. T1ρ imaging can be performed in the forms of T1ρ-weighted image, T1ρ mapping and T1ρ dispersion. T1ρ imaging, particularly at low spin-lock frequency, is sensitive to B0 and B1 inhomogeneity. Various composite spin-lock pulses have been proposed to alleviate the influence of field inhomogeneity so as to reduce the banding-like spin-lock artifacts. T1ρ imaging could be specific absorption rate (SAR) intensive and time consuming. Efforts to address these issues and speed-up data acquisition are being explored to facilitate wider clinical applications. This paper reviews the T1ρ imaging’s basic physic principles, as well as its application for cartilage imaging and intervertebral disc imaging. Compared to more established T2 relaxation time, it has been shown that T1ρ provides more sensitive detection of proteoglycan (PG) loss at early stages of cartilage degeneration. T1ρ has also been shown to provide more sensitive evaluation of annulus fibrosis (AF) degeneration of the discs. PMID:26807369

Quantitative Chemical Exchange Saturation Transfer MRI of Intervertebral Disc in a Porcine Model

PubMed Central

Zhou, Zhengwei; Bez, Maxim; Tawackoli, Wafa; Giaconi, Joseph; Sheyn, Dmitriy; de Mel, Sandra; Maya, Marcel M.; Pressman, Barry D.; Gazit, Zulma; Pelled, Gadi; Gazit, Dan; Li, Debiao

2017-01-01

Purpose Previous studies have associated low pH in interver-tebral discs (IVDs) with discogenic back pain. The purpose of this study was to determine whether quantitative CEST (qCEST) MRI can be used to detect pH changes in IVDs in vivo. Methods The exchange rate ksw between glycosaminoglycan (GAG) protons and water protons was determined from qCEST analysis. Its dependence on pH value was investigated in GAG phantoms with varying pH and concentrations. The relationship between ksw and pH was studied further in vivo in a porcine model on a 3T MR scanner and validated using a pH meter. Sodium lactate was injected into the IVDs to induce various pH values within the discs ranging from 5 to 7. Results Phantom and animal results revealed that ksw measured using qCEST MRI is highly correlated with pH level. In the animal studies, the relationship can be described as ksw =9.2 × 106 × 10−pH + 196.9, R2 = 0.7883. Conclusion The exchange rate between GAG and water protons determined from qCEST MRI is closely correlated with pH value. This technique has the potential to noninvasively measure pH in the IVDs of patients with discogenic pain. PMID:27670140

A Systematic Review of Mesenchymal Stem Cells in Spinal Cord Injury, Intervertebral Disc Repair and Spinal Fusion.

PubMed

Khan, Shujhat; Mafi, Pouya; Mafi, Reza; Khan, Wasim

2018-01-01

Spinal surgery presents a challenge for both neurosurgery and orthopaedic surgery. Due to the heterogeneous differentiation potential of mesenchymal stem cells, there is much interest in the treatment of spine surgery. Animal and human trials focussing on the efficacy of mesenchymal stem cells in spinal cord injury, spine fusion and disc degeneration were included in this systematic review. Published articles up to January 2016 from MEDLINE, PubMed and Ovid were used by searching for specific terms. Of the 2595 articles found, 53 met the selection criteria and were included for analysis (16 on spinal cord injury, 28 on intervertebral disc repair and 9 on spinal fusion). Numerous studies reported better results when the mesenchymal stem cells were used in co-culture with other cells or used in scaffolds. Mesenchymal stem cells were also found to have an immune-modulatory role, which can improve surgical outcome. This systematic review suggests that mesenchymal stem cells can be used safely and effectively for these spinal surgery treatments. Whilst, in certain studies, mesenchymal stem cells did not necessarily show improved results from existing treatments, they provide an alternative option. This can reduce morbidity that arises from current surgical treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Histological and reference system for the analysis of mouse intervertebral disc.

PubMed

Tam, Vivian; Chan, Wilson C W; Leung, Victor Y L; Cheah, Kathryn S E; Cheung, Kenneth M C; Sakai, Daisuke; McCann, Matthew R; Bedore, Jake; Séguin, Cheryle A; Chan, Danny

2018-01-01

A new scoring system based on histo-morphology of mouse intervertebral disc (IVD) was established to assess changes in different mouse models of IVD degeneration and repair. IVDs from mouse strains of different ages, transgenic mice, or models of artificially induced IVD degeneration were assessed. Morphological features consistently observed in normal, and early/later stages of degeneration were categorized into a scoring system focused on nucleus pulposus (NP) and annulus fibrosus (AF) changes. "Normal NP" exhibited a highly cellularized cell mass that decreased with natural ageing and in disc degeneration. "Normal AF" consisted of distinct concentric lamellar structures, which was disrupted in severe degeneration. NP/AF clefts indicated more severe changes. Consistent scores were obtained between experienced and new users. Altogether, our scoring system effectively differentiated IVD changes in various strains of wild-type and genetically modified mice and in induced models of IVD degeneration, and is applicable from the post-natal stage to the aged mouse. This scoring tool and reference resource addresses a pressing need in the field for studying IVD changes and cross-study comparisons in mice, and facilitates a means to normalize mouse IVD assessment between different laboratories. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:233-243, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Gellan gum-based hydrogels for intervertebral disc tissue-engineering applications.

PubMed

Silva-Correia, J; Oliveira, J M; Caridade, S G; Oliveira, J T; Sousa, R A; Mano, J F; Reis, R L

2011-06-01

Intervertebral disc (IVD) degeneration is a challenging clinical problem that urgently demands viable nucleus pulposus (NP) implant materials. The best suited biomaterial for NP regeneration has yet to be identified, but it is believed that biodegradable hydrogel-based materials are promising candidates. In this work, we have developed ionic- and photo-crosslinked methacrylated gellan gum (GG-MA) hydrogels to be used in acellular and cellular tissue-engineering strategies for the regeneration of IVDs. The physicochemical properties of the developed hydrogels were investigated by Fourier-transform infrared spectroscopy, (1) H nuclear magnetic resonance and differential scanning calorimetry. The swelling ability and degradation rate of hydrogels were also analysed in phosphate-buffered saline solution at physiological pH for a period of 30 days. Additionally, the morphology and mechanical properties of the hydrogels were assessed under a scanning electron microscope and dynamic compression, respectively. An in vitro study was carried out to screen possible cytotoxicity of the gellan gum-based hydrogels by culturing rat lung fibroblasts (L929 cells) with hydrogel leachables up to 7 days. The results demonstrated that gellan gum was successfully methacrylated. We observed that the produced GG-MA hydrogels possess improved mechanical properties and lower water uptake ability and degradation rate as compared to gellan gum. This work also revealed that GG-MA hydrogels are non-cytotoxic in vitro, thus being promising biomaterials to be used in IVD tissue-engineering strategies. Copyright © 2010 John Wiley & Sons, Ltd.

The surgical vascular anatomy of the minimally invasive lateral lumbar interbody approach: a cadaveric and radiographic analysis.

PubMed

Alkadhim, Mustafa; Zoccali, Carmine; Abbasifard, Salman; Avila, Mauricio J; Patel, Apar S; Sattarov, Kamran; Walter, Christina M; Baaj, Ali A

2015-11-01

The minimally invasive (MI) lateral lumbar interbody fusion (LLIF) approach has become increasingly popular for the treatment of degenerative lumbar spine disease. The neural anatomy of the lumbar plexus has been studied; however, the pertinent surgical vascular anatomy has not been examined in detail. The goal of this study is to examine the vascular structures that are relevant in relation to the MI-LLIF approach. Anatomic dissection of the lumbar spines and associated vasculature was performed in three embalmed, adult cadavers. Right and left surgeon perspective views during LLIF were for a total of six approaches. During the dissection, all vascular elements were noted and photographed, and anatomical relationships to the vertebral bodies and disc spaces were analyzed. In addition, several axial and sagittal MRI images of the lumbar spine were analyzed to complement the cadaveric analysis. The aorta descends along the left anterior aspect of lumbar vertebra with an average distance of 2.1 cm (range 1.9-2.3 cm) to the center of each intervertebral disc. The vena cava descends along the right anterior aspect of lumbar vertebrates with average distance of 1.4 cm (range 1.3-1.6 cm) to the center of the intervertebral disc. Each vertebral body has two lumbar arteries (direct branches from the aorta); one exits to the left and one to the right side of the vertebral body. The lumbar arteries pass underneath the sympathetic trunk, run in the superior margin of the vertebral body and extend all the way across it, with average length of 3.8 cm (range 2.5-5 cm). The mean distance between the arteries and the inferior plate of the superior disc space is 4.2 mm (range 2-5 mm) and mean distance of 3.1 cm (range 2.8-3.8 cm) between two arteries in adjacent vertebrae. One of the cadavers had an expected normal anatomical variation where the left arteries at L3-L4 anastomosed dorsally of the vertebral bodies at the middle of the intervertebral disc. Understanding the vascular anatomy of the lateral and anterior lumbar spine is paramount for successfully and safely executing the LLIF procedure. It is imperative to identify anatomical variations in lumbar arteries and veins with careful assessment of the preoperative imaging.

Lumbar spine disc height and curvature responses to an axial load generated by a compression device compatible with magnetic resonance imaging

NASA Technical Reports Server (NTRS)

Kimura, S.; Steinbach, G. C.; Watenpaugh, D. E.; Hargens, A. R.

2001-01-01

STUDY DESIGN: Axial load-dependent changes in the lumbar spine of supine healthy volunteers were examined using a compression device compatible with magnetic resonance imaging. OBJECTIVE: To test two hypotheses: Axial loading of 50% body weight from shoulder to feet in supine posture 1) simulates the upright lumbar spine alignment and 2) decreases disc height significantly. SUMMARY OF BACKGROUND DATA: Axial compression on the lumbar spine has significantly narrowed the lumbar dural sac in patients with sciatica, neurogenic claudication or both. METHODS: Using a device compatible with magnetic resonance imaging, the lumbar spine of eight young volunteers, ages 22 to 36 years, was axially compressed with a force equivalent to 50% of body weight, approximating the normal load on the lumbar spine in upright posture. Sagittal lumbar magnetic resonance imaging was performed to measure intervertebral angle and disc height before and during compression. RESULTS: Each intervertebral angle before and during compression was as follows: T12-L1 (-0.8 degrees +/- 2.5 degrees and -1.5 degrees +/- 2.6 degrees ), L1-L2 (0.7 degrees +/- 1.4 degrees and 3.3 degrees +/- 2.9 degrees ), L2-L3 (4.7 degrees +/- 3.5 degrees and 7.3 degrees +/- 6 degrees ), L3-L4 (7.9 degrees +/- 2.4 degrees and 11.1 degrees +/- 4.6 degrees ), L4-L5 (14.3 degrees +/- 3.3 degrees and 14.9 degrees +/- 1.7 degrees ), L5-S1 (25.8 degrees +/- 5.2 degrees and 20.8 degrees +/- 6 degrees ), and L1-S1 (53.4 degrees +/- 11.9 degrees and 57.3 degrees +/- 16.7 degrees ). Negative values reflect kyphosis, and positive values reflect lordosis. A significant difference between values before and during compression was obtained at L3-L4 and L5-S1. There was a significant decrease in disc height only at L4-L5 during compression. CONCLUSIONS: The axial force of 50% body weight in supine posture simulates the upright lumbar spine morphologically. No change in intervertebral angle occurred at L4-L5. However, disc height at L4-L5 decreased significantly during compression.

Finite Element Analysis of the Effect of Epidural Adhesions.

PubMed

Lee, Nam; Ji, Gyu Yeul; Yi, Seong; Yoon, Do Heum; Shin, Dong Ah; Kim, Keung Nyun; Ha, Yoon; Oh, Chang Hyun

2016-07-01

It is well documented that epidural adhesion is associated with spinal pain. However, the underlying mechanism of spinal pain generation by epidural adhesion has not yet been elucidated. To elucidate the underlying mechanism of spinal pain generation by epidural adhesion using a two-dimensional (2D) non-linear finite element (FE) analysis. A finite element analysis. A two-dimensional nonlinear FE model of the herniated lumbar disc on L4/5 with epidural adhesion. A two-dimensional nonlinear FE model of the lumbar spine was developed, consisting of intervertebral discs, dura, spinal nerve, and lamina. The annulus fibrosus and nucleus pulpous were modeled as hyperelastic using the Mooney-Rivlin equation. The FE mesh was generated and analyzed using Abaqus (ABAQUS 6.13.; Hibbitt, Karlsson & Sorenson, Inc., Providence, RI, USA). Epidural adhesion was simulated as rough contact, in which no slip occurred once two surfaces were in contact, between the dura mater and posterior annulus fibrosus. The FE model of adhesion showed significant stress concentration in the spinal nerves, especially on the dorsal root ganglion (DRG). The stress concentration was caused by the lack of adaptive displacement between the dura mater and posterior annulus fibrosus. The peak von Mises stress was higher in the epidural adhesion model (Adhesion, 0.67 vs. Control, 0.46). In the control model, adaptive displacement was observed with decreased stress in the spinal nerve and DRG (with adhesion, 2.59 vs. without adhesion, 3.58, P < 0.00). This study used a 2D non-linear FE model, which simplifies the 3D nature of the human intervertebral disc. In addition, this 2D non-linear FE model has not yet been validated. The current study clearly demonstrated that epidural adhesion causes significantly increased stress in the spinal nerves, especially at the DRG. We believe that the increased stress on the spinal nerve might elicit more pain under similar magnitudes of lumbar disc protrusion.

Consequences of U.S. Navy Diving Mishaps: Air Embolism and Barotrauma.

DTIC Science & Technology

1985-12-01

diver), displacement of the intervertebral disc (I diver), and various combinations of hearing impairment, otitis ", media , otitis externa, and other...hospitalization for otitis media , otitis externa, and other diseases of the ear and mastoid process (8 days later)/ released from active duty (2 yrs, 4

Anterior transcorporeal approach of percutaneous endoscopic cervical discectomy for disc herniation at the C4-C5 levels: a technical note.

PubMed

Deng, Zhong-Liang; Chu, Lei; Chen, Liang; Yang, Jun-Song

2016-05-01

With the continuous development of the spinal endoscopic technique in recent years, percutaneous endoscopic cervical discectomy (PECD) has emerged, which bridges the gap between conservative therapy and traditional surgery and has been mainly divided into the anterior transdiscal approach and the posterior interlaminar access. Because of the relatively greater violation to the anterior nucleus pulposus, there is a higher potential of postoperative intervertebral space decrease in the anterior transdiscal approach than in the posterior interlaminar access. In addition, when the herniated lesion is migrated upward or downward behind the vertebral body, both approaches, and even anterior cervical discectomy and fusion, are impractical, and corpectomy is commonly considered as the only efficacious treatment. Anterior transcorporeal approach under endoscopy could enable an individual and adjustable trajectory within the vertebral body under different conditions of disc herniation preserving the motion of adjacent segment, especially in a migrated or sequestered lesion. This report aimed to first describe a novel anterior transcorporeal approach under endoscopy in which we addressed a migrated disc herniation at the C4-C5 levels. A technical report was carried out. A 37-year-old woman presented with posterior neck pain and weakness of extremities for 9 months. On neurologic examination, tingling sensation and numbness were not obvious. However, the power of extremities was dramatically decreased at a level of 3. Hoffmann sign was positive in the bilateral hand. Magnetic resonance imaging (MRI) showed a huge herniation of the C4-C5 disc compressing the median area of the spinal cord. Besides the C4-C5 disc herniation, preoperative computer tomography (CT) also detected that the herniated disc had partial calcification. A novel anterior transcorporeal approach of PECD, through the vertebral body of C5, was performed to address a migrated disc herniation at the C4-C5 levels. The posterior neck pain was measured using the visual analog scale (VAS). A novel anterior transcorporeal approach under endoscopy was performed to address a migrated disc herniation at the C4-C5 levels. This operation was accomplished in 75 minutes. Postoperatively, the drainage tube was retained into the drilling hole for 24 hours to avoid the possibility of hematoma. The patient was advised to wear a neck collar for 3 weeks. Immediately after the operation, the posterior neck pain improved from VAS 7/10 preoperatively to 3/10, and the myodynamia of extremities improved stepwise. At 12 hours postoperatively, the range of motion was also improved. In the further follow-up, the patient has completely recovered from the preoperative symptoms, whose myodynamia of extremities is normal. Besides the postoperative MRI, a total removal of the herniated disc and the transcorporeal drilling tunnel are observed in CT. At postoperative 3-month follow-up, neither disc space narrowing nor instability was observed on CT, in which the bone defect after drilling tunnelwas partially decreased, indicating bone healing. There were no surgery-related complications, such as dysphagia, Horner syndrome, recurrent laryngeal nerve palsy, vagus nerve injury, tracheoesophageal injury, or cervical hematocele. As a supplement to the described surgical approach of PECD, the transcorporeal approach is a novel access for the treatment of cervical intervertebral disc herniation. Among the advantages of this approach are providing a clear visual field during microendoscopic surgery and decreasing the intraoperative iatrogenic injury to, as well as avoiding violation to the discal tissue. Theoretically, the potential of secondary decline of intervertebral height is low. However, as the limitation of one case shows, whether this transcorporeal approach is efficacious and reliable should be verified in a further comparative cohort study with a large volume of patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Update on the Notochord Including its Embryology, Molecular Development, and Pathology: A Primer for the Clinician

PubMed Central

Ramesh, Tushar; Nagula, Sai V; Saker, Erfanul; Shoja, Mohammadali; Loukas, Marios; Oskouian, Rod J; Tubbs, R. Shane

2017-01-01

The notochord is a rod-like embryological structure, which plays a vital role in the development of the vertebrate. Though embryological, remnants of this structure have been observed in the nucleus pulposus of the intervertebral discs of normal adults. Pathologically, these remnants can give rise to slow-growing and recurrent notochord-derived tumors called chordomas. Using standard search engines, the literature was reviewed regarding the anatomy, embryology, molecular development, and pathology of the human notochord. Clinicians who interpret imaging or treat patients with pathologies linked to the notochord should have a good working knowledge of its development and pathology. PMID:28480155

Lactoferricin mediates anti-inflammatory and anti-catabolic effects via inhibition of IL-1 and LPS activity in the intervertebral disc.

PubMed

Kim, Jae-Sung; Ellman, Michael B; Yan, Dongyao; An, Howard S; Kc, Ranjan; Li, Xin; Chen, Di; Xiao, Guozhi; Cs-Szabo, Gabriella; Hoskin, David W; Buechter, Doug D; Van Wijnen, Andre J; Im, Hee-Jeong

2013-09-01

The catabolic cytokine interleukin-1 (IL-1) and endotoxin lipopolysaccharide (LPS) are well-known inflammatory mediators involved in degenerative disc disease, and inhibitors of IL-1 and LPS may potentially be used to slow or prevent disc degeneration in vivo. Here, we elucidate the striking anti-catabolic and anti-inflammatory effects of bovine lactoferricin (LfcinB) in the intervertebral disc (IVD) via antagonism of both IL-1 and LPS-mediated catabolic activity using in vitro and ex vivo analyses. Specifically, we demonstrate the biological counteraction of LfcinB against IL-1 and LPS-mediated proteoglycan (PG) depletion, matrix-degrading enzyme production, and enzyme activity in long-term (alginate beads) and short-term (monolayer) culture models using bovine and human nucleus pulposus (NP) cells. LfcinB significantly attenuates the IL-1 and LPS-mediated suppression of PG production and synthesis, and thus restores PG accumulation and pericellular matrix formation. Simultaneously, LfcinB antagonizes catabolic factor mediated induction of multiple cartilage-degrading enzymes, including MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5, in bovine NP cells at both mRNA and protein levels. LfcinB also suppresses the catabolic factor-induced stimulation of oxidative and inflammatory factors such as iNOS, IL-6, and toll-like receptor-2 (TLR-2) and TLR-4. Finally, the ability of LfcinB to antagonize IL-1 and LPS-mediated suppression of PG is upheld in an en bloc intradiscal microinjection model followed by ex vivo organ culture using both mouse and rabbit IVD tissue, suggesting a potential therapeutic benefit of LfcinB on degenerative disc disease in the future. Copyright © 2013 Wiley Periodicals, Inc.

Development and Validation of a Bioreactor System for Dynamic Loading and Mechanical Characterization of Whole Human Intervertebral Discs in Organ Culture

PubMed Central

Walter, BA; Illien-Junger, S; Nasser, P; Hecht, AC; Iatridis, JC

2014-01-01

Intervertebral disc (IVD) degeneration is a common cause of back pain, and attempts to develop therapies are frustrated by lack of model systems that mimic the human condition. Human IVD organ culture models can address this gap, yet current models are limited since vertebral endplates are removed to maintain cell viability, physiological loading is not applied, and mechanical behaviors are not measured. This study aimed to (i) establish a method for isolating human IVDs from autopsy with intact vertebral endplates, and (ii) develop and validate an organ culture loading system for human or bovine IVDs. Human IVDs with intact endplates were isolated from cadavers within 48 hours of death and cultured for up to 21 days. IVDs remained viable with ~80% cell viability in nucleus and annulus regions. A dynamic loading system was designed and built with the capacity to culture 9 bovine or 6 human IVDs simultaneously while applying simulated physiologic loads (maximum force: 4kN) and measuring IVD mechanical behaviors. The loading system accurately applied dynamic loading regimes (RMS error <2.5N and total harmonic distortion <2.45%), and precisely evaluated mechanical behavior of rubber and bovine IVDs. Bovine IVDs maintained their mechanical behavior and retained >85% viable cells throughout the 3 week culture period. This organ culture loading system can closely mimic physiological conditions and be used to investigate response of living human and bovine IVDs to mechanical and chemical challenges and to screen therapeutic repair techniques. PMID:24725441

Does core mobility of lumbar total disc arthroplasty influence sagittal and frontal intervertebral displacement? Radiologic comparison with fixed-core prosthesis

PubMed Central

Delécrin, Joël; Allain, Jérôme; Beaurain, Jacques; Steib, Jean-Paul; Chataigner, Hervé; Aubourg, Lucie; Huppert, Jean; Ameil, Marc; Nguyen, Jean-Michel

2009-01-01

Background An artificial disc prosthesis is thought to restore segmental motion in the lumbar spine. However, it is reported that disc prosthesis can increase the intervertebral translation (VT). The concept of the mobile-core prosthesis is to mimic the kinematic effects of the migration of the natural nucleus and therefore core mobility should minimize the VT. This study explored the hypothesis that core translation should influence VT and that a mobile core prosthesis may facilitate physiological motion. Methods Vertebral translation (measured with a new method presented here), core translation, range of motion (ROM), and distribution of flexion-extension were measured on flexion-extension, neutral standing, and lateral bending films in 89 patients (63 mobile-core [M]; 33 fixed-core [F]). Results At L4-5 levels the VT with M was lower than with F and similar to the VT of untreated levels. At L5-S1 levels the VT with M was lower than with F but was significantly different compared to untreated levels. At M levels a strong correlation was found between VT and core translation; the VT decreases as the core translation increases. At F levels the VT increases as the ROM increases. No significant difference was found between the ROM of untreated levels and levels implanted with either M or F. Regarding the mobility distribution with M and F we observed a deficit in extension at L5-S1 levels and a similar distribution at L4-5 levels compared to untreated levels. Conclusion The intervertebral mobility was different between M and F. The M at L4-5 levels succeeded to replicate mobility similar to L4-5 untreated levels. The M at L5-S1 succeeded in ROM, but failed regarding VT and mobility distribution. Nevertheless M minimized VT at L5-S1 levels. The F increased VT at both L4-5 and L5-S1. Clinical Relevance This study validates the concept that the core translation of an artificial lumbar disc prosthesis minimizes the VT. PMID:25802632

Dysregulated miR-127-5p contributes to type II collagen degradation by targeting matrix metalloproteinase-13 in human intervertebral disc degeneration.

PubMed

Hua, Wen-Bin; Wu, Xing-Huo; Zhang, Yu-Kun; Song, Yu; Tu, Ji; Kang, Liang; Zhao, Kang-Cheng; Li, Shuai; Wang, Kun; Liu, Wei; Shao, Zeng-Wu; Yang, Shu-Hua; Yang, Cao

2017-08-01

Intervertebral disc degeneration (IDD) is a chronic disease associated with the degradation of extracellular matrix (ECM). Matrix metalloproteinase (MMP)-13 is a major enzyme that mediates the degradation of ECM components. MMP-13 has been predicted to be a potential target of miR-127-5p. However, the exact function of miR-127-5p in IDD is still unclear. We designed this study to evaluate the correlation between miR-127-5p level and the degeneration of human intervertebral discs and explore the potential mechanisms. miR-127-5p levels and MMP-13 mRNA levels were detected by quantitative real-time polymerase chain reaction (qPCR). To determine whether MMP-13 is a target of miR-127-5p, dual luciferase reporter assays were performed. miR-127-5p mimic and miR-127-5p inhibitor were used to overexpress or downregulate miR-127-5p expression in human NP cells, respectively. Small interfering RNA (siRNA) was used to knock down MMP-13 expression in human NP cells. Type II collagen expression in human NP cells was detected by qPCR, western blotting, and immunofluorescence staining. We confirmed that miR-127-5p was significantly downregulated in nucleus pulposus (NP) tissue of degenerative discs and its expression was inversely correlated with MMP-13 mRNA levels. We reveal that MMP-13 may act as a target of miR-127-5p. Expression of miR-127-5p was inversely correlated with type II collagen expression in human NP cells. Moreover, suppression of MMP-13 expression by siRNA blocked downstream signaling and increased type II collagen expression. Dysregulated miR-127-5p contributed to the degradation of type II collagen by targeting MMP-13 in human IDD. Our findings highlight that miR-127-5p may serve as a new therapeutic target in IDD. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

The activL® Artificial Disc: a next-generation motion-preserving implant for chronic lumbar discogenic pain

PubMed Central

Yue, James J; Garcia, Rolando; Miller, Larry E

2016-01-01

Degeneration of the lumbar intervertebral discs is a leading cause of chronic low back pain in adults. Treatment options for patients with chronic lumbar discogenic pain unresponsive to conservative management include total disc replacement (TDR) or lumbar fusion. Until recently, only two lumbar TDRs had been approved by the US Food and Drug Administration − the Charité Artificial Disc in 2004 and the ProDisc-L Total Disc Replacement in 2006. In June 2015, a next-generation lumbar TDR received Food and Drug Administration approval − the activL® Artificial Disc (Aesculap Implant Systems). Compared to previous-generation lumbar TDRs, the activL® Artificial Disc incorporates specific design enhancements that result in a more precise anatomical match and allow a range of motion that better mimics the healthy spine. The results of mechanical and clinical studies demonstrate that the activL® Artificial Disc results in improved mechanical and clinical outcomes versus earlier-generation artificial discs and compares favorably to lumbar fusion. The purpose of this report is to describe the activL® Artificial Disc including implant characteristics, intended use, surgical technique, postoperative care, mechanical testing, and clinical experience to date. PMID:27274317

Clinical Characterization of Patients With Autosomal Dominant Short Stature due to Aggrecan Mutations

PubMed Central

Gkourogianni, Alexandra; Andrew, Melissa; Tyzinski, Leah; Crocker, Melissa; Douglas, Jessica; Dunbar, Nancy; Fairchild, Jan; Funari, Mariana F. A.; Heath, Karen E.; Jorge, Alexander A. L.; Kurtzman, Tracey; LaFranchi, Stephen; Lalani, Seema; Lebl, Jan; Lin, Yuezhen; Los, Evan; Newbern, Dorothee; Nowak, Catherine; Olson, Micah; Popovic, Jadranka; Průhová, Štěpánka; Elblova, Lenka; Quintos, Jose Bernardo; Segerlund, Emma; Sentchordi, Lucia; Shinawi, Marwan; Stattin, Eva-Lena; Swartz, Jonathan; del Angel, Ariadna González; Cuéllar, Sinhué Diaz; Hosono, Hidekazu; Sanchez-Lara, Pedro A.; Hwa, Vivian; Baron, Jeffrey; Dauber, Andrew

2017-01-01

Context: Heterozygous mutations in the aggrecan gene (ACAN) cause autosomal dominant short stature with accelerated skeletal maturation. Objective: We sought to characterize the phenotypic spectrum and response to growth-promoting therapies. Patients and Methods: One hundred three individuals (57 females, 46 males) from 20 families with autosomal dominant short stature and heterozygous ACAN mutations were identified and confirmed using whole-exome sequencing, targeted next-generation sequencing, and/or Sanger sequencing. Clinical information was collected from the medical records. Results: Identified ACAN variants showed perfect cosegregation with phenotype. Adult individuals had mildly disproportionate short stature [median height, −2.8 standard deviation score (SDS); range, −5.9 to −0.9] and a history of early growth cessation. The condition was frequently associated with early-onset osteoarthritis (12 families) and intervertebral disc disease (9 families). No apparent genotype–phenotype correlation was found between the type of ACAN mutation and the presence of joint complaints. Childhood height was less affected (median height, −2.0 SDS; range, −4.2 to −0.6). Most children with ACAN mutations had advanced bone age (bone age − chronologic age; median, +1.3 years; range, +0.0 to +3.7 years). Nineteen individuals had received growth hormone therapy with some evidence of increased growth velocity. Conclusions: Heterozygous ACAN mutations result in a phenotypic spectrum ranging from mild and proportionate short stature to a mild skeletal dysplasia with disproportionate short stature and brachydactyly. Many affected individuals developed early-onset osteoarthritis and degenerative disc disease, suggesting dysfunction of the articular cartilage and intervertebral disc cartilage. Additional studies are needed to determine the optimal treatment strategy for these patients. PMID:27870580

Poly(γ-glutamic acid) and poly(γ-glutamic acid)-based nanocomplexes enhance type II collagen production in intervertebral disc.

PubMed

Antunes, Joana C; Pereira, Catarina Leite; Teixeira, Graciosa Q; Silva, Ricardo V; Caldeira, Joana; Grad, Sibylle; Gonçalves, Raquel M; Barbosa, Mário A

2017-01-01

Intervertebral disc (IVD) degeneration often leads to low back pain, which is one of the major causes of disability worldwide, affecting more than 80% of the population. Although available treatments for degenerated IVD decrease symptoms' progression, they fail to address the underlying causes and to restore native IVD properties. Poly(γ-glutamic acid) (γ-PGA) has recently been shown to support the production of chondrogenic matrix by mesenchymal stem/stromal cells. γ-PGA/chitosan (Ch) nanocomplexes (NCs) have been proposed for several biomedical applications, showing advantages compared with either polymer alone. Hence, this study explores the potential of γ-PGA and γ-PGA/Ch NCs for IVD regeneration. Nucleotomised bovine IVDs were cultured ex vivo upon injection of γ-PGA (pH 7.4) and γ-PGA/Ch NCs (pH 5.0 and pH 7.4). Tissue metabolic activity and nucleus pulposus DNA content were significantly reduced when NCs were injected in acidic-buffered solution (pH 5.0). However, at pH 7.4, both γ-PGA and NCs promoted sulphated glycosaminoglycan production and significant type II collagen synthesis, as determined at the protein level. This study is a first proof of concept that γ-PGA and γ-PGA/Ch NCs promote recovery of IVD native matrix, opening new perspectives on the development of alternative therapeutic approaches for IVD degeneration.

Magnetic resonance imaging versus computed tomography to plan hemilaminectomies in chondrodystrophic dogs with intervertebral disc extrusion.

PubMed

Noyes, Julie A; Thomovsky, Stephanie A; Chen, Annie V; Owen, Tina J; Fransson, Boel A; Carbonneau, Kira J; Matthew, Susan M

2017-10-01

To determine the influence of preoperative computed tomography (CT) versus magnetic resonance (MR) on hemilaminectomies planned to treat thoracolumbar (TL) intervertebral disc (IVD) extrusions in chondrodystrophic dogs. Prospective clinical study. Forty chondrodystrophic dogs with TL IVD extrusion and preoperative CT and MR studies. MR and CT images were randomized and reviewed by 4 observers masked to the dog's identity and corresponding imaging studies. Observers planned the location along the spine, side, and extent (number of articular facets to be removed) based on individual reviews of CT and MR studies. Intra-observer agreement was determined between overall surgical plan, location, side, and size of the hemilaminectomy planned on CT versus MR of the same dog. Similar surgical plans were developed based on MR versus CT in 43.5%-66.6% of dogs, depending on the observer. Intra-observer agreement in location, side, and size of the planned hemilaminectomy based on CT versus MR ranged between 48.7%-66.6%, 87%-92%, and 51.2%-71.7% of dogs, respectively. Observers tended to plan larger laminectomy defects based on MR versus CT of the same dog. Findings from this study indicated considerable differences in hemilaminectomies planned on preoperative MR versus CT imaging. Surgical location and size varied the most; the side of planned hemilaminectomies was most consistent between imaging modalities. © 2017 The American College of Veterinary Surgeons.

Cervical lordosis: the effect of age and gender.

PubMed

Been, Ella; Shefi, Sara; Soudack, Michalle

2017-06-01

Cervical lordosis is of great importance to posture and function. Neck pain and disability is often associated with cervical lordosis malalignment. Surgical procedures involving cervical lordosis stabilization or restoration must take into account age and gender differences in cervical lordosis architecture to avoid further complications. Therefore, the purpose of the present study was to evaluate differences in cervical lordosis between males and females from childhood to adulthood. This is a retrospective descriptive study. A total of 197 lateral cervical radiographs of patients aged 6-50 years were examined. These were divided into two age groups: the younger group (76 children aged 6-19; 48 boys and 28 girls) and the adult group (121 adults aged 20-50; 61 males and 60 females). The retrospective review of the radiographs was approved by the institutional review board. On each radiograph, six lordosis angles were measured including total cervical lordosis (FM-C7), upper (FM-C3; C1-C3) and lower (C3-C7) cervical lordosis, C1-C7 lordosis, and the angle between foramen magnum and the atlas (FM-C1). Wedging angles of each vertebral body (C3-C7) and intervertebral discs (C2-C3 to C6-C7) were also measured. Vertebral body wedging and intervertebral disc wedging were defined as the sum of the individual body or disc wedging of C3 to C7, respectively. Each cervical radiograph was classified according to four postural categories: A-lordotic, B-straight, C-double curve, and D-kyphotic. The total cervical lordosis of males and females was similar. Males had smaller upper cervical lordosis (FM-C3) and higher lower cervical lordosis (C3-C7) than females. The sum of vertebral body wedging of males and females is kyphotic (anterior height smaller than posterior height). Males had more lordotic intervertebral discs than females. Half of the adults (51%) had lordotic cervical spine, 41% had straight spine, and less than 10% had double curve or kyphotic spine. Children had similar total cervical lordosis (FM-C7) to adults. The sum of vertebral body wedging for children was more kyphotic-by 7°-than that of adults, whereas the sum of intervertebral disc wedging in children was more lordotic-by11°-than that of adults. Seventy-one percent of the children had lordotic cervical spine, 23% had straight spine, and less than 6% had double curve spine. Gender differences are already apparent in children as girls had higher upper cervical lordosis (FM-C3; C1-C3) than boys do. Although the total cervical lordosis (FM-C7) did not change between age groups, and between males and females, the internal architecture of the cervical lordosis changed significantly. Practitioners before neck stabilization procedures or correction and restoration should therefore take into account the gender and age differences in cervical lordosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Mechanical Restoration and Failure Analyses of a Hydrogel and Scaffold Composite Strategy for Annulus Fibrosus Repair

PubMed Central

Long, Rose G; Bürki, Alexander; Zysset, Philippe; Eglin, David; Grijpma, Dirk W.; Blanquer, Sebastien BG; Hecht, Andrew C; Iatridis, James C

2015-01-01

Unrepaired defects in the annulus fibrosus of intervertebral discs are associated with degeneration and persistent back pain. A clinical need exists for a disc repair strategy that can seal annular defects, be easily delivered during surgical procedures, and restore biomechanics with low risk of herniation. Multiple annulus repair strategies were developed using poly(trimethylene carbonate) scaffolds optimized for cell delivery, polyurethane membranes designed to prevent herniation, and fibrin-genipin adhesive tuned to annulus fibrosus shear properties. This three-part study evaluated repair strategies for biomechanical restoration, herniation risk and failure mode in torsion, bending and compression at physiological and hyper-physiological loads using a bovine injury model. Fibrin-genipin hydrogel restored some torsional stiffness, bending ROM and disc height loss, with negligible herniation risk and failure was observed histologically at the fibrin-genipin mid-substance following rigorous loading. Scaffold-based repairs partially restored biomechanics, but had high herniation risk even when stabilized with sutured membranes and failure was observed histologically at the interface between scaffold and fibrin-genipin adhesive. Fibrin-genipin was the simplest annulus fibrosus repair solution evaluated that involved an easily deliverable adhesive that filled irregularly-shaped annular defects and partially restored disc biomechanics with low herniation risk, suggesting further evaluation for disc repair may be warranted. PMID:26577987

Lumbar Spine Musculoskeletal Physiology and Biomechanics During Simulated Military Operations

DTIC Science & Technology

2014-06-01

scanner to quantify muscle quality and intervertebral disc degeneration. Significant decreases in lumbar lordosis were found through all levels except L1...L2 when sitting. When prone on elbows, the only increase in lumbar lordosis was found at L5-S1. An increase in fat fraction of the erector spinae

The deformation behavior of the cervical spine segment

NASA Astrophysics Data System (ADS)

Kolmakova, T. V.; Rikun, Yu. A.

2017-09-01

The paper describes the model of the cervical spine segment (C3-C4) and the calculation results of its deformation behavior at flexion. The segment model was built based on the experimental literature data taking into account the presence of the cortical and cancellous bone tissue of vertebral bodies. Degenerative changes of the intervertebral disk (IVD) were simulated through a reduction of the disc height and an increase of Young's modulus. The construction of the geometric model of the cervical spine segment and the calculations of the stress-strain state were carried out in the ANSYS software complex. The calculation results show that the biggest protrusion of the IVD in bending direction of segment is observed when IVD height is reduced. The disc protrusion is reduced with an increase of Young's modulus. The largest protrusion in the direction of flexion of the segment is the intervertebral disk with height of 4.3 mm and elastic modulus of 2.5 MPa. The results of the study can be useful to specialists in the field of biomechanics, medical materials science and prosthetics.

Noncoding RNAs in human intervertebral disc degeneration: An integrated microarray study.

PubMed

Liu, Xu; Che, Lu; Xie, Yan-Ke; Hu, Qing-Jie; Ma, Chi-Jiao; Pei, Yan-Jun; Wu, Zhi-Gang; Liu, Zhi-Heng; Fan, Li-Ying; Wang, Hai-Qiang

2015-09-01

Accumulating evidence indicates that noncoding RNAs play important roles in a multitude of biological processes. The striking findings of miRNAs (microRNAs) and lncRNAs (long noncoding RNAs) as members of noncoding RNAs open up an exciting era in the studies of gene regulation. More recently, the reports of circRNAs (circular RNAs) add fuel to the noncoding RNAs research. Human intervertebral disc degeneration (IDD) is a main cause of low back pain as a disabling spinal disease. We have addressed the expression profiles if miRNAs, lncRNAs and mRNAs in IDD (Wang et al., J Pathology, 2011 and Wan et al., Arthritis Res Ther, 2014). Furthermore, we thoroughly analysed noncoding RNAs, including miRNAs, lncRNAs and circRNAs in IDD using the very same samples. Here we delineate in detail the contents of the aforementioned microarray analyses. Microarray and sample annotation data were deposited in GEO under accession number GSE67567 as SuperSeries. The integrated analyses of these noncoding RNAs will shed a novel light on coding-noncoding regulatory machinery.

Injectable hydrogels with high fixed charge density and swelling pressure for nucleus pulposus repair: biomimetic glycosaminoglycan analogues.

PubMed

Sivan, S S; Roberts, S; Urban, J P G; Menage, J; Bramhill, J; Campbell, D; Franklin, V J; Lydon, F; Merkher, Y; Maroudas, A; Tighe, B J

2014-03-01

The load-bearing biomechanical role of the intervertebral disc is governed by the composition and organization of its major macromolecular components, collagen and aggrecan. The major function of aggrecan is to maintain tissue hydration, and hence disc height, under the high loads imposed by muscle activity and body weight. Key to this role is the high negative fixed charge of its glycosaminoglycan side chains, which impart a high osmotic pressure to the tissue, thus regulating and maintaining tissue hydration and hence disc height under load. In degenerate discs, aggrecan degrades and is lost from the disc, particularly centrally from the nucleus pulposus. This loss of fixed charge results in reduced hydration and loss of disc height; such changes are closely associated with low back pain. The present authors developed biomimetic glycosaminoglycan analogues based on sulphonate-containing polymers. These biomimetics are deliverable via injection into the disc where they polymerize in situ, forming a non-degradable, nuclear "implant" aimed at restoring disc height to degenerate discs, thereby relieving back pain. In vitro, these glycosaminoglycan analogues possess appropriate fixed charge density, hydration and osmotic responsiveness, thereby displaying the capacity to restore disc height and function. Preliminary biomechanical tests using a degenerate explant model showed that the implant adapts to the space into which it is injected and restores stiffness. These hydrogels mimic the role taken by glycosaminoglycans in vivo and, unlike other hydrogels, provide an intrinsic swelling pressure, which can maintain disc hydration and height under the high and variable compressive loads encountered in vivo. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Contribution of facet joints, axial compression, and composition to human lumbar disc torsion mechanics.

PubMed

Bezci, Semih E; Eleswarapu, Ananth; Klineberg, Eric O; O'Connell, Grace D

2018-02-12

Stresses applied to the spinal column are distributed between the intervertebral disc and facet joints. Structural and compositional changes alter stress distributions within the disc and between the disc and facet joints. These changes influence the mechanical properties of the disc joint, including its stiffness, range of motion, and energy absorption under quasi-static and dynamic loads. There have been few studies evaluating the role of facet joints in torsion. Furthermore, the relationship between biochemical composition and torsion mechanics is not well understood. Therefore, the first objective of this study was to investigate the role of facet joints in torsion mechanics of healthy and degenerated human lumbar discs under a wide range of compressive preloads. To achieve this, each disc was tested under four different compressive preloads (300-1200 N) with and without facet joints. The second objective was to develop a quantitative structure-function relationship between tissue composition and torsion mechanics. Facet joints have a significant contribution to disc torsional stiffness (∼60%) and viscoelasticity, regardless of the magnitude of axial compression. The findings from this study demonstrate that annulus fibrosus GAG content plays an important role in disc torsion mechanics. A decrease in GAG content with degeneration reduced torsion mechanics by more than an order of magnitude, while collagen content did not significantly influence disc torsion mechanics. The biochemical-mechanical and compression-torsion relationships reported in this study allow for better comparison between studies that use discs of varying levels of degeneration or testing protocols and provide important design criteria for biological repair strategies. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Are magnetic resonance imaging or radiographic findings correlated with clinical prognosis in spinal cord neuropathy?

PubMed Central

Neshat Halati, Fatemeh; Vajhi, Alireza; Molazem, Mohammad; Dehghan, Mohammad Mehdi; Ansari, Fereshteh

2016-01-01

Dogs presented to the Small Animal Hospital of Veterinary Medicine, University of Tehran were included in the present study if spinal or intervertebral disc involvement was suspected. Clinical signs were recorded as well as general information of the patient such as age, breed and sex. Sixty dogs were examined radiographically and two standard orthogonal lateral and ventrodorsal projections were taken from the suspected region. Then magnetic resonance imaging (MRI) was performed for all patients. Agreement between MRI and radiographic findings, comparison of sex and breed with diagnostic imaging grades, comparison between diagnostic imaging grades and mean age, recovery rate after surgery or medical treatment, effects of diagnostic imaging severity grades on surgical or medical referrals were evaluated statistically. There were no significant association between age, sex and breed and frequency of the intervertebral disk disease. Intervertebral disc involvements between L2-L3 and T13-L1 were estimated as the most frequent sites of involvements. Sensitivity and specificity of radiography were evaluated 90.0% and 46.0%, respectively, by considering the MRI as a gold standard modality. There was a significant association between severity of disease in the MRI with referral to surgery and medical treatment. The recovery rate after surgery was significantly higher than medical treatment. These results can be used as a foundation for other studies with more focuses on details of injury and larger group of patients. PMID:27872724

Prevalence and pattern of radiographic intervertebral disc degeneration in Vietnamese: a population-based study.

PubMed

Ho-Pham, Lan T; Lai, Thai Q; Mai, Linh D; Doan, Minh C; Pham, Hoa N; Nguyen, Tuan V

2015-06-01

Intervertebral disc degeneration (IDD) is one of the most common skeletal disorders, yet few data are available in Asian populations. We sought to assess the prevalence and pattern of radiographic IDD in a Vietnamese population. This population-based cross-sectional investigation involved 170 men and 488 women aged ≥40 years, who were randomly sampled from the Ho Chi Minh City (Vietnam). Anthropometric data, clinical history and self-reported back and neck pain were ascertained by a questionnaire. Plain radiographs (from the cervical spine, thoracic spine to the lumbar spine) were examined for the presence of disc space narrowing and/or osteophytosis using the Kellgren-Lawrence (KL) grading system. The presence of radiographic IDD was defined if the KL grade was 2 or greater in at least one disc. The prevalence of radiographic IDD was 62.4% (n = 106) in men and 54.7% (n = 267) in women. The most frequently affected site was the lumbar spine with prevalence being 50.6 and 43.2% in men and women, respectively. The prevalence of IDD increased with advancing age: 18.8% among those aged 40-49 years, and increased to 83.4% in those aged ≥60 years. Self-reported neck pain and lower back pain were found in 30 and 44% of individuals, respectively. There was no statistically significant association between self-reported neck pain and cervical spine OA. These data suggest that radiographic IDD is highly prevalent in the Vietnamese population, and that self-reported back pain is not a sensitive indicator of IDD.

Regulation of gene expression in intervertebral disc cells by low and high hydrostatic pressure.

PubMed

Neidlinger-Wilke, Cornelia; Würtz, Karin; Urban, Jill P G; Börm, Wolfgang; Arand, Markus; Ignatius, Anita; Wilke, Hans-Joachim; Claes, Lutz E

2006-08-01

Intervertebral disc structures are exposed to wide ranges of intradiscal hydrostatic pressure during different loading exercises and are at their minimum during lying or relaxed sitting and at maximum during lifting weights with a round back. We hypothesize that these different loading magnitudes influence the intervertebral disc (IVD) by alteration of disc matrix turnover depending on their magnitudes. Therefore the aim of this study was to assess changes in gene expression of human nucleus cells after the application of low hydrostatic pressure (0.25 MPa) and high hydrostatic pressure (2.5 MPa). IVD cells isolated from the nucleus of human (n = 18) and bovine (n = 24 from four animals) disc biopsies were seeded into three-dimensional collagen type-I matrices and exposed to the different loading magnitudes by specially developed pressure chambers. The lower pressure range (0.25 MPa, 30 min, 0.1 Hz) was applied with a recently published device by using an external compression cylinder. For the application of higher loads (2.5 MPa, 30 min, 0.1 Hz) the cell-loaded collagen gels were sealed into sterile bags with culture medium and stimulated in a newly developed water-filled compression cylinder by using a loading frame. These methods allowed the comparison of loading regimes in a wide physiological range under an equal three-dimensional culture conditions. Cells were harvested 24 h after the end of stimulation and changes in the expression of genes known to influence IVD matrix turnover (collagen-I, collagen-II, aggrecan, MMP1, MMP2, MMP3, MMP13) were analyzed by real-time RT-PCR. A Wilcoxon signed-rank test(1) and a Wilcoxon 2-sample test(2) were performed to detect differences between the stimulated and control samples(1) and differences between low and high hydrostatic pressure(2). Multiple testing was considered by adjusting the p value appropriately. Both regimes of hydrostatic pressure influenced gene expression in nucleus cells with opposite tendencies for the matrix forming proteins aggrecan and collagen type-I in response to the two different pressure magnitudes: Low hydrostatic-pressure (0.25 MPa) tended to increase collagen-I and aggrecan expression of human nucleus cells (P < 0.05) but only to a small degree. High hydrostatic pressure (2.5 MPa) tended to decrease gene expression of all anabolic proteins with significant effects on aggrecan expression of nucleus cells (P = 0.004). Low hydrostatic pressure had no influence on the expression of matrix metalloproteinases (MMP1, MMP2, MMP3 and MMP13). In contrast, high hydrostatic pressure tended to increase the expression of MMP1, MMP3 and MMP13 of human nucleus cells with high individual-individual variations. The decreased expression of aggrecan (P = 0.008) and collagen type II (P = 0.023) and the increased MMP3 expression (P = 0.008) in response to high hydrostatic pressure could be confirmed in additional experiments with bovine nucleus cells. These results suggest that hydrostatic pressure as one of the physiological stimuli of the IVD may influence matrix turnover in a magnitude dependent way. Low hydrostatic pressure (0.25 MPa) has quite small influences with a tendency to anabolic effects, whereas high hydrostatic pressure (2.5 MPa) tends to decrease the matrix protein expression with a tendency to increase some matrix-turnover enzymes. Therefore, hydrostatic pressure may regulate disc matrix turnover in a dose-dependent way.

Lumbar annulus fibrosus biomechanical characterization in healthy children by ultrasound shear wave elastography.

PubMed

Vergari, Claudio; Dubois, Guillaume; Vialle, Raphael; Gennisson, Jean-Luc; Tanter, Mickael; Dubousset, Jean; Rouch, Philippe; Skalli, Wafa

2016-04-01

Intervertebral disc (IVD) is key to spine biomechanics, and it is often involved in the cascade leading to spinal deformities such as idiopathic scoliosis, especially during the growth spurt. Recent progress in elastography techniques allows access to non-invasive measurement of cervical IVD in adults; the aim of this study was to determine the feasibility and reliability of shear wave elastography in healthy children lumbar IVD. Elastography measurements were performed in 31 healthy children (6-17 years old), in the annulus fibrosus and in the transverse plane of L5-S1 or L4-L5 IVD. Reliability was determined by three experienced operators repeating measurements. Average shear wave speed in IVD was 2.9 ± 0.5 m/s; no significant correlations were observed with sex, age or body morphology. Intra-operator repeatability was 5.0 % while inter-operator reproducibility was 6.2 %. Intraclass correlation coefficient was higher than 0.9 for each operator. Feasibility and reliability of IVD shear wave elastography were demonstrated. The measurement protocol is compatible with clinical routine and the results show the method's potential to give an insight into spine deformity progression and early detection. • Intervertebral disc mechanical properties are key to spine biomechanics • Feasibility of shear wave elastography in children lumbar disc was assessed • Measurement was fast and reliable • Elastography could represent a novel biomarker for spine pathologies.

Shh signaling from the nucleus pulposus is required for the postnatal growth and differentiation of the mouse intervertebral disc.

PubMed

Dahia, Chitra Lekha; Mahoney, Eric; Wylie, Christopher

2012-01-01

Intervertebral discs (IVD) are essential components of the vertebral column. They maintain separation, and provide shock absorbing buffers, between adjacent vertebrae, while also allowing movements between them. Each IVD consists of a central semi-liquid nucleus pulposus (NP) surrounded by a multi-layered fibrocartilagenous annulus fibrosus (AF). Although the IVDs grow and differentiate after birth along with the vertebral column, little is known about the mechanism of this. Understanding the signals that control normal IVD growth and differentiation would also provide potential therapies for degenerative disc disease, which is the major cause of lower back pain and affects a large proportion of the population. In this work, we show that during postnatal growth of the mouse, Sonic hedgehog (Shh) signaling from the NP cells controls many aspects of growth and differentiation of both the NP cells themselves and of the surrounding AF, and that it acts, at least partly, by regulating other signaling pathways in the NP and AF. Recent studies have shown that the NP cells arise from the embryonic notochord, which acts as a major signaling center in the embryo. This work shows that this notochord-derived tissue continues to carry out a major signaling function in the postnatal body and that the IVDs are signaling centers, in addition to their already known functions in the mechanics of vertebral column function.

Structure-Specific Movement Patterns in Patients With Chronic Low Back Dysfunction Using Lumbar Combined Movement Examination.

PubMed

Monie, Aubrey P; Price, Roger I; Lind, Christopher R P; Singer, Kevin P

2017-06-01

A test-retest cohort study was conducted to assess the use of a novel computer-aided, combined movement examination (CME) to measure change in low back movement after pain management intervention in 17 cases of lumbar spondylosis. Additionally we desired to use a CME normal reference range (NRR) to compare and contrast movement patterns identified from 3 specific structural pathologic conditions: intervertebral disc, facet joint, and nerve root compression. Computer-aided CME was used before and after intervention, in a cohort study design, to record lumbar range of movement along with pain, disability, and health self-report questionnaires in 17 participants who received image-guided facet, epidural, and/or rhizotomy intervention. In the majority of cases, CME was reassessed after injection together with 2 serial self-reports after an average of 2 and 14 weeks. A minimal clinically important difference of 30% was used to interpret meaningful change in self-reports. A CME NRR (n = 159) was used for comparison with the 17 cases. Post hoc observation included subgrouping cases into 3 discrete pathologic conditions, intervertebral disc, facet dysfunction, and nerve root compression, in order to report intergroup differences in CME movement. Seven of the 17 participants stated that a "combined" movement was their most painful CME direction. Self-report outcome data indicated that 4 participants experienced significant improvement in health survey, 5 improved by ≥30% on low back function, and 8 reported that low back pain was more bothersome than stiffness, 6 of whom achieved the minimal clinically important difference for self-reported pain. Subgrouping of cases into structure-specific groups provided insight to different CME movement patterns. The use of CME assists in identifying atypical lumbar movement relative to an age and sex NRR. Data from this study, exemplified by representative case studies, provide preliminary evidence for distinct intervertebral disc, facet joint, and nerve root compression CME movement patterns in cases of chronic lumbar spondylosis. Copyright © 2017. Published by Elsevier Inc.

The immediate reduction in low back pain intensity following lumbar joint mobilization and prone press-ups is associated with increased diffusion of water in the L5-S1 intervertebral disc.

PubMed

Beattie, Paul F; Arnot, Cathy F; Donley, Jonathan W; Noda, Harmony; Bailey, Lane

2010-05-01

Single-group, prospective, repeated-measures design. To determine differences in the changes of diffusion of water in the L5-S1 intervertebral disc between subjects with nonspecific low back pain (LBP) who reported an immediate reduction in pain intensity of 2 or greater on an 11-point (0-10) numeric rating scale after a 10-minute session of lumbar joint mobilization, followed by prone press-up exercises, compared to those who did not report an immediate reduction in pain intensity of 2 or greater on the pain scale. Combining lumbar joint mobilization and prone press-up exercises is a common intervention for patients with LBP; however, there is conflicting evidence regarding the effectiveness and efficacy of this approach. Increased knowledge of the physiologic effects of the combined use of these treatments, and the relationship to pain reports, can lead to refinement of their clinical application. Twenty adults, aged 22 to 54, participated in this study. All subjects reported LBP of at least 2 on an 11-point (0-10) verbally administered numeric rating scale at the time of enrollment in the study and were classified as being candidates for the combination of joint mobilization and prone press-ups. Subjects underwent T2- and diffusion-weighted lumbar magnetic resonance imaging scans before and immediately after receiving a 10-minute session of lumbar pressures in a posterior-to-anterior direction and prone press-up exercises. Subjects who reported a decrease in current pain intensity of 2 or greater immediately following treatment were classified as immediate responders, while the remainder were classified as not-immediate responders. The apparent diffusion coefficient, representing the diffusion of water in the nucleus pulposis, was calculated from the midsagittal diffusion-weighted images. Following treatment, immediate responders (n = 10) had a mean increase in the apparent diffusion coefficient in the middle portion of the L5-S1 intervertebral disc of 4.2% compared to a mean decrease of 1.6% for the not-immediate responders (P<.005). In a group of subjects with LBP, who were classified as being candidates for extension-based treatment, the report of an immediate reduction in pain intensity of 2/10 of greater after a treatment of posterior-to-anterior-directed pressures, followed by prone press-up exercises, was associated with an increase in diffusion of water in the nuclear region of the L5-S1 intervertebral disc. Subjects who did not report a pain reduction of at least 2/10 did not have a change in diffusion. J Orthop Sports Phys Ther 2010;40(5):256-264, Epub 12 March 2010. doi:10.2519/jospt.2010.3284.

Biomechanical Characterization of an Annulus Sparing Spinal Disc Prosthesis

PubMed Central

Buttermann, Glenn R.; Beaubien, Brian P.

2009-01-01

Background Context Current spine arthroplasty devices, require disruption of the annulus fibrosus for implantation. Preliminary studies of a unique annulus sparing intervertebral prosthetic disc (IPD), found that preservation of the annulus resulted in load sharing of the annulus with the prosthesis. Purpose Determine flexibility of the IPD versus fusion constructs in normal and degenerated human spines. Study design/Setting Biomechanical comparison of motion segments in the intact, fusion and mechanical nucleus replacement states for normal and degenerated states. Patient setting Thirty lumbar motion segments. Outcomes Measures Intervertebral height; motion segment range-of-motion (ROM), neutral zone (NZ), stiffness. Methods Motion segments had multi-directional flexibility testing to 7.5 Nm for intact discs, discs reconstructed using the IPD (n=12), or after anterior/posterior fusions (n=18). Interbody height and axial compression stiffness changes were determined for the reconstructed discs by applying axial compression to 1500 N. Analysis included stratifying results to normal mobile vs. rigid degenerated intact motion segments. Results The mean interbody height increase was 1.5 mm for IPD reconstructed discs. vs 3.0 mm for fused segments. Axial compression stiffness was 3.0 ± 0.9 kN/mm for intact compared to 1.2 ± 0.4 kN/mm for IPD reconstructed segments. Reconstructed disc ROM was 9.0° ± 3.7° in flexion-extension, 10.6° ± 3.4° in lateral bending and 2.8° ± 1.4° in axial torsion which was similar to intact values and significantly greater than respective fusion values (p<0.001). Mobile intact segments exhibited significantly greater rotation after fusion vs. their more rigid counterparts (p<0.05), however, intact motion was not related to motion after IPD reconstruction. The NZ and rotational stiffness followed similar trends. Differences in NZ between mobile and rigid intact specimens tended to decrease in the IPD reconstructed state. Conclusion The annulus sparing IPD generally reproduced the intact segment biomechanics in terms of ROM, NZ, and stiffness. Furthermore, the IPD reconstructed discs imparted stability by maintaining a small neutral zone. The IPD reconstructed discs were significantly less rigid than the fusion constructs and may be an attractive alternative for the treatment of DDD. PMID:19540816

A miniature fiber optic pressure sensor for intradiscal pressure measurements of rodents

NASA Astrophysics Data System (ADS)

Nesson, Silas; Yu, Miao; Hsieh, Adam H.

2007-04-01

Lower back pain continues to be a leading cause of disability in people of all ages, and has been associated with degenerative disc disease. It is well accepted that mechanical stress, among other factors, can play a role in the development of disc degeneration. Pressures generated in the intervertebral disc have been measured both in vivo and in vitro for humans and animals. However, thus far it has been difficult to measure pressure experimentally in rodent discs due to their small size. With the prevalent use of rodent tail disc models in mechanobiology, it is important to characterize the intradiscal pressures generated with externally applied stresses. In this paper, a miniature fiber optic Fabry-Perot interferometric pressure sensor with an outer diameter of 360 μm was developed to measure intradiscal pressures in rat caudal discs. A low coherence interferometer based optical system was used, which includes a broadband light source, a high-speed spectrometer, and a Fabry-Perot sensor. The sensor employs a capillary tube, a flexible, polymer diaphragm coated with titanium as a partial mirror, and a fiber tip as another mirror. The pressure induced deformation of the diaphragm results in a cavity length change of the Fabry-Perot interferometer which can be calculated from the wavelength shift of interference fringes. The sensor exhibited good linearity with small applied pressures. Our validation experiments show that owing to the small size, inserting the sensor does not disrupt the annulus fibrosus and will not alter intradiscal pressures generated. Measurements also demonstrate the feasibility of using this sensor to quantify external load intradiscal pressure relationships in small animal discs.

[Building an effective nonlinear three-dimensional finite-element model of human thoracolumbar spine].

PubMed

Zeng, Zhi-Li; Cheng, Li-Ming; Zhu, Rui; Wang, Jian-Jie; Yu, Yan

2011-08-23

To build an effective nonlinear three-dimensional finite-element (FE) model of T(11)-L(3) segments for a further biomechanical study of thoracolumbar spine. The CT (computed tomography) scan images of healthy adult T(11)-L(3) segments were imported into software Simpleware 2.0 to generate a triangular mesh model. Using software Geomagic 8 for model repair and optimization, a solid model was generated into the finite element software Abaqus 6.9. The reasonable element C3D8 was selected for bone structures. Created between bony endplates, the intervertebral disc was subdivided into nucleus pulposus and annulus fibrosus (44% nucleus, 56% annulus). The nucleus was filled with 5 layers of 8-node solid elements and annulus reinforced by 8 crisscross collagenous fiber layers. The nucleus and annulus were meshed by C3D8RH while the collagen fibers meshed by two node-truss elements. The anterior (ALL) and posterior (PLL) longitudinal ligaments, flavum (FL), supraspinous (SSL), interspinous (ISL) and intertransverse (ITL) ligaments were modeled with S4R shell elements while capsular ligament (CL) was modeled with 3-node shell element. All surrounding ligaments were represented by envelope of 1 mm uniform thickness. The discs and bone structures were modeled with hyper-elastic and elasto-plastic material laws respectively while the ligaments governed by visco-elastic material law. The nonlinear three-dimensional finite-element model of T(11)-L(3) segments was generated and its efficacy verified through validating the geometric similarity and disc load-displacement and stress distribution under the impact of violence. Using ABAQUS/ EXPLICIT 6.9 the explicit dynamic finite element solver, the impact test was simulated in vitro. In this study, a 3-dimensional, nonlinear FE model including 5 vertebrae, 4 intervertebral discs and 7 ligaments consisted of 78 887 elements and 71 939 nodes. The model had good geometric similarity under the same conditions. The results of FEM intervertebral disc load-displacement curve were similar to those of in vitro test. The stress distribution results of vertebral cortical bone, posterior complex and cancellous bone were similar to those of other static experiments in a dynamic impact test under the observation of stress cloud. With the advantages of high geometric and mechanical similarity and complete thoracolumbar, hexahedral meshes, nonlinear finite element model may facilitate the impact loading test for a further dynamic analysis of injury mechanism for thoracolumbar burst fracture.

Degenerative Changes of the Spine of Pilots of the RNLAF

DTIC Science & Technology

2000-08-01

views of the spine taken in standing 7-3 Table 2 Classification of disorders Disorder Levels General: Osteo-arthrosis / Spondylosis / Arthrosis...Deformans Cervical, thoracic, lumbar Scoliosis Cervical, thoracic, lumbar Abnormal alignment Cervical, lumbar Scheuermann’s disease / Enchondrosis Thoracic... lumbar Specific: Degenerative changes in the intervertebral disc / Discopathy Cervical, thoracic, lumbar Presence of Osteophyte’s / Osteophytic

Human Disc Nucleus Properties and Vertebral Endplate Permeability

PubMed Central

Rodriguez, Azucena G.; Slichter, Chloe K.; Acosta, Frank L.; Rodriguez-Soto, Ana E.; Burghardt, Andrew J.; Majumdar, Sharmila; Lotz, Jeffrey C.

2010-01-01

Study of human cadaveric discs quantifying endplate permeability and porosity and correlating these with measures of disc quality: cell density, proteoglycan content, and overall degeneration. Permeability and porosity increased with age and were not correlated with cell density or overall degeneration, suggesting that endplate calcification may not accelerate disc degeneration. Study Design Experimental quantification of relationships between vertebral endplate morphology, permeability, disc cell density, glycosaminoglycan content and degeneration in samples harvested from human cadaveric spines. Objective To test the hypothesis that variation in endplate permeability and porosity contribute to changes in intervertebral disc cell density and overall degeneration. Summary of Background Data Cells within the intervertebral disc are dependent on diffusive exchange with capillaries in the adjacent vertebral bone. Previous findings suggest that blocked routes of transport negatively affect disc quality, yet there are no quantitative relationships between human vertebral endplate permeability, porosity, cell density and disc degeneration. Such relationships would be valuable for clarifying degeneration risk factors, and patient features that may impede efforts at disc tissue engineering. Methods Fifty-one motion segments were harvested from 13 frozen cadaveric human lumbar spines (32 to 85 years) and classified for degeneration using the MRI-based Pfirrmann scale. A cylindrical core was harvested from the center of each motion segment that included vertebral bony and cartilage endplates along with adjacent nucleus tissue. The endplate mobility, a type of permeability, was measured directly using a custom-made permeameter before and after the cartilage endplate was removed. Cell density within the nucleus tissue was estimated using the picogreen method while the nuclear GAG content was quantified using the DMMB technique. Specimens were imaged at 8 μm resolution using microCT, bony porosity was calculated. Analysis of variance, linear regression, and multiple comparison tests were used to analyze the data. Results Nucleus cell density increased as the disc height decreased (R2=0.13; p=0.01) but was not related to subchondral bone porosity (p>0.5), total mobility (p>0.4) or age (p>0.2). When controlling for disc height however, a significant, negative effect of age on cell density was observed (p=0.03). In addition to this, GAG content decreased with age non-linearly (R2=0.83, p<0.0001) and a cell function measurement, GAGs/cell decreased with degeneration (R2=0.24; p<0.0001). Total mobility (R2=0.14; p<0.01) and porosity (R2=0.1, p<0.01) had a positive correlation with age. Conclusion Although cell density increased with degeneration, cell function indicated that GAGs/cell decreased. Since permeability and porosity increase with age and degeneration, this implies that cell dysfunction, rather than physical barriers to transport, accelerate disc disease. PMID:21240044

Foxa1 and Foxa2 are required for formation of the intervertebral discs.

PubMed

Maier, Jennifer A; Lo, YinTing; Harfe, Brian D

2013-01-01

The intervertebral disc (IVD) is composed of 3 main structures, the collagenous annulus fibrosus (AF), which surrounds the gel-like nucleus pulposus (NP), and hyaline cartilage endplates, which are attached to the vertebral bodies. An IVD is located between each vertebral body. Degeneration of the IVD is thought to be a major cause of back pain, a potentially chronic condition for which there exist few effective treatments. The NP forms from the embryonic notochord. Foxa1 and Foxa2, transcription factors in the forkhead box family, are expressed early during notochord development. However, embryonic lethality and the absence of the notochord in Foxa2 null mice have precluded the study of potential roles these genes may play during IVD formation. Using a conditional Foxa2 allele in conjunction with a tamoxifen-inducible Cre allele (ShhcreER(T2)), we removed Foxa2 from the notochord of E7.5 mice null for Foxa1. Foxa1(-/-);Foxa2(c/c);ShhcreER(T2) double mutant animals had a severely deformed nucleus pulposus, an increase in cell death in the tail, decreased hedgehog signaling, defects in the notochord sheath, and aberrant dorsal-ventral patterning of the neural tube. Embryos lacking only Foxa1 or Foxa2 from the notochord were indistinguishable from control animals, demonstrating a functional redundancy for these genes in IVD formation. In addition, we provide in vivo genetic evidence that Foxa genes are required for activation of Shh in the notochord.

Deletion of Mecom in mouse results in early-onset spinal deformity and osteopenia.

PubMed

Juneja, Subhash C; Vonica, Alin; Zeiss, Caroline; Lezon-Geyda, Kimberly; Yatsula, Bogdan; Sell, David R; Monnier, Vincent M; Lin, Sharon; Ardito, Thomas; Eyre, David; Reynolds, David; Yao, Zhenqiang; Awad, Hani A; Yu, Hongbo; Wilson, Michael; Honnons, Sylvie; Boyce, Brendan F; Xing, Lianping; Zhang, Yi; Perkins, Archibald S

2014-03-01

Recent studies have indicated a role for a MECOM allele in susceptibility to osteoporotic fractures in humans. We have generated a mutation in Mecom in mouse (termed ME(m1)) via lacZ knock-in into the upstream transcription start site for the gene, resulting in disruption of Mds1 and Mds1-Evi1 transcripts, but not of Evi1 transcripts. We demonstrate that ME(m1/m1) mice have severe kyphoscoliosis that is reminiscent of human congenital or primary kyphoscoliosis. ME(m1/m1) mice appear normal at birth, but by 2weeks, they exhibit a slight lumbar lordosis and narrowed intervertebral space. This progresses to severe lordosis with disc collapse and synostosis, together with kyphoscoliosis. Bone formation and strength testing show that ME(m1/m1) mice have normal bone formation and composition but are osteopenic. While endochondral bone development is normal, it is markedly dysplastic in its organization. Electron micrographs of the 1week postnatal intervertebral discs reveals marked disarray of collagen fibers, consistent with an inherent weakness in the non-osseous connective tissue associated with the spine. These findings indicate that lack of ME leads to a complex defect in both osseous and non-osseous musculoskeletal tissues, including a marked vertebral osteopenia, degeneration of the IVD, and disarray of connective tissues, which is likely due to an inherent inability to establish and/or maintain components of these tissues. Copyright © 2013 Elsevier Inc. All rights reserved.

Foxa1 and Foxa2 Are Required for Formation of the Intervertebral Discs

PubMed Central

Maier, Jennifer A.; Lo, YinTing; Harfe, Brian D.

2013-01-01

The intervertebral disc (IVD) is composed of 3 main structures, the collagenous annulus fibrosus (AF), which surrounds the gel-like nucleus pulposus (NP), and hyaline cartilage endplates, which are attached to the vertebral bodies. An IVD is located between each vertebral body. Degeneration of the IVD is thought to be a major cause of back pain, a potentially chronic condition for which there exist few effective treatments. The NP forms from the embryonic notochord. Foxa1 and Foxa2, transcription factors in the forkhead box family, are expressed early during notochord development. However, embryonic lethality and the absence of the notochord in Foxa2 null mice have precluded the study of potential roles these genes may play during IVD formation. Using a conditional Foxa2 allele in conjunction with a tamoxifen-inducible Cre allele (ShhcreERT2), we removed Foxa2 from the notochord of E7.5 mice null for Foxa1. Foxa1−/−;Foxa2c/c;ShhcreERT2 double mutant animals had a severely deformed nucleus pulposus, an increase in cell death in the tail, decreased hedgehog signaling, defects in the notochord sheath, and aberrant dorsal-ventral patterning of the neural tube. Embryos lacking only Foxa1 or Foxa2 from the notochord were indistinguishable from control animals, demonstrating a functional redundancy for these genes in IVD formation. In addition, we provide in vivo genetic evidence that Foxa genes are required for activation of Shh in the notochord. PMID:23383217

Cobb Angle Progression in Adolescent Scoliosis Begins at the Intervertebral Disc

PubMed Central

Will, Ryan E; Stokes, Ian A; Qiu, Xing; Walker, Matthew R.; Sanders, James O

2009-01-01

Study Design Longitudinal radiographic study of patients with progressive idiopathic scoliosis. Objective To determine the relative contributions of vertebral and disc wedging to the increase in Cobb angle during 3 phases of adolescent skeletal growth and maturation. Summary of Background Data Both disc wedging and vertebral body wedging are found in progressive scoliosis, but their relative contribution to curve progression over time is unknown. Which occurs first is important for understanding how scoliosis progresses and for developing methods to halt progression. Previous studies have not properly identified maturity and provide conflicting results. Methods Eighteen girls were followed through their adolescent growth spurt with serial spine and hand skeletal age radiographs. Each Cobb angle was divided into disc wedge angles and vertebral wedge angles. The corresponding hand radiographs provided a measure of maturity level, the Digital Skeletal Age (DSA). The disc versus bone contributions to the Cobb angle were then compared during 3 growth phases: prior to the growth spurt, during the growth spurt and after the growth spurt. Significance of relative changes was assessed with the Wilcoxon two-sided mean rank test. Results Prior to the growth spurt, there was no difference in relative contributions of the disc and the bone (3° vs 0°, p=0.38) to curve progression. During the growth spurt, the mean disc component progressed significantly more than that of the vertebrae (15° vs 0°, p=0.0002). This reversed following the growth spurt with the vertebral component progressing more than the disc (10° vs 0°, p=0.01). Conclusion Adolescent idiopathic scoliosis initially increases through disc wedging during the rapid growth spurt with progressive vertebral wedging occurring later. PMID:19940737

Evaluation of a new approach to compute intervertebral disc height measurements from lateral radiographic views of the spine.

PubMed

Allaire, Brett T; DePaolis Kaluza, M Clara; Bruno, Alexander G; Samelson, Elizabeth J; Kiel, Douglas P; Anderson, Dennis E; Bouxsein, Mary L

2017-01-01

Current standard methods to quantify disc height, namely distortion compensated Roentgen analysis (DCRA), have been mostly utilized in the lumbar and cervical spine and have strict exclusion criteria. Specifically, discs adjacent to a vertebral fracture are excluded from measurement, thus limiting the use of DCRA in studies that include older populations with a high prevalence of vertebral fractures. Thus, we developed and tested a modified DCRA algorithm that does not depend on vertebral shape. Participants included 1186 men and women from the Framingham Heart Study Offspring and Third Generation Multidetector CT Study. Lateral CT scout images were used to place 6 morphometry points around each vertebra at 13 vertebral levels in each participant. Disc heights were calculated utilizing these morphometry points using DCRA methodology and our modified version of DCRA, which requires information from fewer morphometry points than the standard DCRA. Modified DCRA and standard DCRA measures of disc height are highly correlated, with concordance correlation coefficients above 0.999. Both measures demonstrate good inter- and intra-operator reproducibility. 13.9 % of available disc heights were not evaluable or excluded using the standard DCRA algorithm, while only 3.3 % of disc heights were not evaluable using our modified DCRA algorithm. Using our modified DCRA algorithm, it is not necessary to exclude vertebrae with fracture or other deformity from disc height measurements as in the standard DCRA. Modified DCRA also yields identical measurements to the standard DCRA. Thus, the use of modified DCRA for quantitative assessment of disc height will lead to less missing data without any loss of accuracy, making it a preferred alternative to the current standard methodology.

Correlation study between facet joint cartilage and intervertebral discs in early lumbar vertebral degeneration using T2, T2* and T1ρ mapping

PubMed Central

Zhang, Yi; Hu, Jianzhong; Duan, Chunyue; Hu, Ping; Lu, Hongbin; Peng, Xianjing

2017-01-01

Recent advancements in magnetic resonance imaging have allowed for the early detection of biochemical changes in intervertebral discs and articular cartilage. Here, we assessed the feasibility of axial T2, T2* and T1ρ mapping of the lumbar facet joints (LFJs) to determine correlations between cartilage and intervertebral discs (IVDs) in early lumbar vertebral degeneration. We recruited 22 volunteers and examined 202 LFJs and 101 IVDs with morphological (sagittal and axial FSE T2-weighted imaging) and axial biochemical (T2, T2* and T1ρ mapping) sequences using a 3.0T MRI scanner. IVDs were graded using the Pfirrmann system. Mapping values of LFJs were recorded according to the degeneration grades of IVDs at the same level. The feasibility of T2, T2* and T1ρ in IVDs and LFJs were analyzed by comparing these mapping values across subjects with different rates of degeneration using Kruskal-Wallis tests. A Pearson’s correlation analysis was used to compare T2, T2* and T1ρ values of discs and LFJs. We found excellent reproducibility in the T2, T2* and T1ρ values for the nucleus pulposus (NP), anterior and posterior annulus fibrosus (PAF), and LFJ cartilage (intraclass correlation coefficients 0.806–0.955). T2, T2* and T1ρ mapping (all P<0.01) had good Pfirrmann grade performances in the NP with IVD degeneration. LFJ T2* values were significantly different between grades I and IV (PL = 0.032, PR = 0.026), as were T1ρ values between grades II and III (PL = 0.002, PR = 0.006) and grades III and IV (PL = 0.006, PR = 0.001). Correlations were moderately negative for T1ρ values between LFJ cartilage and NP (rL = −0.574, rR = −0.551), and between LFJ cartilage and PAF (rL = −0.551, rR = −0.499). T1ρ values of LFJ cartilage was weakly correlated with T2 (r = 0.007) and T2* (r = −0.158) values. Overall, we show that axial T1ρ effectively assesses early LFJ cartilage degeneration. Using T1ρ analysis, we propose a link between LFJ degeneration and IVD NP or PAF changes. PMID:28570641

Lumbar intervertebral disc allograft transplantation: long-term mobility and impact on the adjacent segments.

PubMed

Huang, Yong-Can; Xiao, Jun; Lu, William W; Leung, Victor Y L; Hu, Yong; Luk, Keith D K

2017-03-01

Fresh-frozen intervertebral disc (IVD) allograft transplantation has been successfully performed in the human cervical spine. Whether this non-fusion technology could truly decrease adjacent segment disease is still unknown. This study evaluated the long-term mobility of the IVD-transplanted segment and the impact on the adjacent spinal segments in a goat model. Twelve goats were used. IVD allograft transplantation was performed at lumbar L4/L5 in 5 goats; the other 7 goats were used as the untreated control (5) and for the supply of allografts (2). Post-operation lateral radiographs of the lumbar spine in the neutral, full-flexion and full-extension positions were taken at 1, 3, 6, 9 and 12 months. Disc height (DH) of the allograft and the adjacent levels was calculated and range of motion (ROM) was measured using the Cobb's method. The anatomy of the adjacent discs was observed histologically. DH of the transplanted segment was decreased significantly after 3 months but no further reduction was recorded until the final follow-up. No obvious alteration was seen in the ROM of the transplanted segment at different time points with the ROM at 12 months being comparable to that of the untreated control. The DH and ROM in the adjacent segments were well maintained during the whole observation period. At post-operative 12 months, the ROM of the adjacent levels was similar to that of the untreated control and the anatomical morphology was well preserved. Lumbar IVD allograft transplantation in goats could restore the segmental mobility and did not negatively affect the adjacent segments after 12 months.

Whole-body vibration of mice induces progressive degeneration of intervertebral discs associated with increased expression of Il-1β and multiple matrix degrading enzymes.

PubMed

McCann, Matthew R; Veras, Matthew A; Yeung, Cynthia; Lalli, Gurkeet; Patel, Priya; Leitch, Kristyn M; Holdsworth, David W; Dixon, S Jeffrey; Séguin, Cheryle A

2017-05-01

Whole-body vibration (WBV) is a popular fitness trend based on claims of increased muscle mass, weight loss and reduced joint pain. Following its original implementation as a treatment to increase bone mass in patients with osteoporosis, WBV has been incorporated into clinical practice for musculoskeletal disorders, including back pain. However, our recent studies revealed damaging effects of WBV on joint health in a murine model. In this report, we examined potential mechanisms underlying disc degeneration following exposure of mice to WBV. Ten-week-old male mice were exposed to WBV (45 Hz, 0.3 g peak acceleration, 30 min/day, 5 days/week) for 4 weeks, 8 weeks, or 4 weeks WBV followed by 4 weeks recovery. Micro-computed tomography (micro-CT), histological, and gene expression analyses were used to assess the effects of WBV on spinal tissues. Exposure of mice to 4 or 8 weeks of WBV did not alter total body composition or induce significant changes in vertebral bone density. On the other hand, WBV-induced intervertebral disc (IVD) degeneration, associated with decreased disc height and degenerative changes in the annulus fibrosus (AF) that did not recover within 4 weeks after cessation of WBV. Gene expression analysis showed that WBV for 8 weeks induced expression of Mmp3, Mmp13, and Adamts5 in IVD tissues, changes preceded by increased expression of Il-1β. Progressive IVD degeneration induced by WBV was associated with increased expression of Il-1β within the IVD that preceded Mmp and Adamts gene induction. Moreover, WBV-induced IVD degeneration is not reversed following cessation of vibration. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Circadian factors BMAL1 and RORα control HIF-1α transcriptional activity in nucleus pulposus cells: implications in maintenance of intervertebral disc health

PubMed Central

Suyama, Kaori; Silagi, Elizabeth S.; Choi, Hyowon; Sakabe, Kou; Mochida, Joji; Shapiro, Irving M.; Risbud, Makarand V.

2016-01-01

BMAL1 and RORα are major regulators of the circadian molecular oscillator. Since previous work in other cell types has shown cross talk between circadian rhythm genes and hypoxic signaling, we investigated the role of BMAL1 and RORα in controlling HIF-1-dependent transcriptional responses in NP cells that exist in the physiologically hypoxic intervertebral disc. HIF-1-dependent HRE reporter activity was further promoted by co-transfection with either BMAL1 or RORα. In addition, stable silencing of BMAL1 or inhibition of RORα activity resulted in decreased HRE activation. Inhibition of RORα also modulated HIF1α-TAD activity. Interestingly, immunoprecipitation studies showed no evidence of BMAL1, CLOCK or RORα binding to HIF-1α in NP cells. Noteworthy, stable silencing of BMAL1 as well as inhibition of RORα decreased expression of select HIF-1 target genes including VEGF, PFKFB3 and Eno1. To delineate if BMAL1 plays a role in maintenance of disc health, we studied the spinal phenotype of BMAL1-null mice. The lumbar discs of null mice evidenced decreased height, and several parameters associated with vertebral trabecular bone quality were also affected in nulls. In addition, null animals showed a higher ratio of cells to matrix in NP tissue and hyperplasia of the annulus fibrosus. Taken together, our results indicate that BMAL1 and RORα form a regulatory loop in the NP and control HIF-1 activity without direct interaction. Importantly, activities of these circadian rhythm molecules may play a role in the adaptation of NP cells to their unique niche. PMID:27049729

A Randomized Controlled Trial to Assess Pain and Magnetic Resonance Imaging-Based (MRI-Based) Structural Spine Changes in Low Back Pain Patients After Yoga Practice

PubMed Central

Telles, Shirley; Bhardwaj, Abhishek K.; Gupta, Ram K.; Sharma, Sachin K.; Monro, Robin; Balkrishna, Acharya

2016-01-01

Background The present study aimed at determining whether 12 weeks of yoga practice in patients with chronic LBP and MRI-based degenerative changes would result in differences in: (i) self-reported pain, anxiety, and spinal flexibility; and (ii) the structure of the discs or vertebrae. Material/Methods Sixty-two persons with MRI-proven degenerative intervertebral discs (group mean ±S.D., 36.2±6.4 years; 30 females) were randomly assigned to yoga and control groups. However, testing was conducted on only 40 subjects, so only their data are included in this study. The assessments were: self-reported pain, state anxiety, spinal flexibility, and MRI of the lumbosacral spine, performed using a 1.5 Tesla system with a spinal surface column. The yoga group was taught light exercises, physical postures, breathing techniques, and yoga relaxation techniques for 1 hour daily for 3 months. No intervention was given to the control group except for routine medical care. A repeated-measures analysis of variance (ANOVA) with post hoc analyses (which was Bonferroni-adjusted) was used. The Ethics Committee of Patanjali Research Foundation had approved the study which had been registered in the Clinical Trials Registry of India (CTRI/2012/11/003094). Results The yoga group showed a significant reduction in self-reported pain and state anxiety in a before/after comparison at 12 weeks. A few patients in both groups showed changes in the discs and vertebrae at post-intervention assessment. Conclusions Within 12 weeks, yoga practice reduced pain and state anxiety but did not alter MRI-proven changes in the intervertebral discs and in the vertebrae.

Lactoferricin mediates Anti-Inflammatory and Anti-Catabolic Effects via Inhibition of IL-1 and LPS Activity in the Intervertebral Disc†

PubMed Central

Kim, Jae-Sung; Ellman, Michael B.; Yan, Dongyao; An, Howard S.; Kc, Ranjan; Li, Xin; Chen, Di; Xiao, Guozhi; Cs-Zabo, Gabriella; Hoskin, David W.; Buechter, D.D.; Van Wijnen, Andre J.; Im, Hee-Jeong

2013-01-01

The catabolic cytokine interleukin-1 (IL-1) and endotoxin lipopolysaccharide (LPS) are well-known inflammatory mediators involved in degenerative disc disease, and inhibitors of IL-1 and LPS may potentially be used to slow or prevent disc degeneration in vivo. Here, we elucidate the striking anti-catabolic and anti-inflammatory effects of bovine lactoferricin (LfcinB) in the intervertebral disc (IVD) via antagonism of both IL-1 and LPS-mediated catabolic activity using in vitro and ex vivo analyses. Specifically, we demonstrate the biological counteraction of LfcinB against IL-1 and LPS-mediated proteoglycan (PG) depletion, matrix-degrading enzyme production and enzyme activity in long-term (alginate beads) and short-term (monolayer) culture models using bovine and human nucleus pulposus (NP) cells. LfcinB significantly attenuates the IL-1 and LPS-mediated suppression of PG production and synthesis, and thus restores PG accumulation and pericellular matrix formation. Simultaneously, LfcinB antagonizes catabolic factor mediated induction of multiple cartilage-degrading enzymes, including MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5, in bovine NP cells at both mRNA and protein levels. LfcinB also suppresses the catabolic factor-induced stimulation of oxidative and inflammatory factors such as iNOS, IL-6, and toll-like receptor-2 (TLR-2) and TLR-4. Finally, the ability of LfcinB to antagonize IL-1 and LPS-mediated suppression of PG is upheld in an en bloc intradiscal microinjection model followed by ex vivo organ culture using both mouse and rabbit IVD tissue, suggesting a potential therapeutic benefit of LfcinB on degenerative disc disease in the future. PMID:23460134

The significance of calcified fibrocartilage on the cortical endplate of the translational sheep spine model.

PubMed

Sinclair, Sarina K; Bell, Spencer; Epperson, Richard Tyler; Bloebaum, Roy D

2013-05-01

To gain an understanding of the vertebral cortical endplate and factors that may affect the ability to achieve skeletal attachment to intervertebral implants and fusion, this study aimed to characterize the hypermineralized tissue on the cortical endplate of the vertebral body on a commonly used animal model. Skeletally mature sheep were injected with tetracycline prior to euthanasia and the C2-C3, T5-T6, and L2-L3 spinal motion segments were excised and prepared. Vertebral tissues were imaged using backscatter electron (BSE) imaging, histology, and tetracycline labeling was used to assess bone remodeling within different tissue layers. It was determined that the hypermineralized tissue layer was calcified fibrocartilage (CFC). No tetracycline labels were identified in the CFC layer, in contrast to single and double labels that were present in the underlying bone, indicating the CFC present on the cortical endplate was not being actively remodeled. The average thickness of the CFC layer was 146.3 ± 70.53 µm in the cervical region, 98.2 ± 40.29 µm in the thoracic region, and 150.89 ± 69.25 µm in the lumbar region. This difference in thickness may be attributed to the regional biomechanical properties of the spine. Results from this investigation indicate the presence of a nonremodeling tissue on the cortical endplate of the vertebral body in sheep spines, which attaches the intervertebral disc to the vertebrae. This tissue, if not removed, would likely prevent successful bony attachment to an intervertebral device in spinal fusion studies and total disc replacement surgeries. Copyright © 2013 Wiley Periodicals, Inc.

Implant detectibility of intervertebral disc spacers in post fusion MRI: evaluation of the MRI scan quality by using a scoring system--an in vitro study.

PubMed

Ernstberger, Thorsten; Heidrich, Gabert; Schultz, Wolfgang; Grabbe, Eckhardt

2007-02-01

Intervertebral spacers for anterior spine fusion are made of different materials, such as titanium and cobalt chromium alloys and carbon fiber-reinforced polymers. Implant-related susceptibility artifacts can decrease the quality of MRI scans. The aim of this cadaveric study was to demonstrate the extent that implant-related MRI artifacting affects the postfusion differentiation of determined regions of interest (ROIs). In six cadaveric porcine spines, we evaluated the postimplantation MRI scans of a titanium, cobalt-chromium and carbon spacer that differed in shape and surface qualities. A spacer made of human cortical bone was used as a control. A defined evaluation unit was divided into ROIs to characterize the spinal canal as well as the intervertebral disc space. Considering 15 different MRI sequences read independently by an interobserver-validated team of specialists the artifact-affected image quality of the median MRI slice was rated on a score of 0-3. A maximum score of 18 points (100%) for the determined ROIs was possible. Turbo spin echo sequences produced the best scores for all spacers and the control. Only the control achieved a score of 100%. For the determined ROI maximum scores for the cobalt-chromium, titanium and carbon spacers were 24%, 32% and 84%, respectively. By using favored T1 TSE sequences the carbon spacer showed a clear advantage in postfusion spinal imaging. Independent of artifact dimensions, the scoring system used allowed us to create an implant-related ranking of MRI scan quality in reference to the bone control.

Sideflexion induced lumbar spine conjunct rotation and its influencing factors.

PubMed

Vicenzino, G; Twomey, L

1993-01-01

Twenty motion segments from four male post mortem subjects with a mean age of 29 years were moved into the lumbar spine test positions of extension/left sideflexion, extension/right sideflexion, flexion/left sideflexion and flexion/right sideflexion Jheconjunct rotation (CR) that occurred was measured from a photographic record. The results indicated that the direction of the CR of the whole lumbar spine (ie between L1 and S1) was significantly different between the flexed and extended lumbar spine position. The direction of the CR was also significantly different between the different intervertebral motion segment levels. There was no relationship between CR and zygapophyseal joint geometry or intervertebral disc degeneration. Copyright © 1993 Australian Physiotherapy Association. Published by . All rights reserved.

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.

PubMed

Stelzeneder, David; Welsch, Goetz Hannes; Kovács, Balázs Krisztián; Goed, Sabine; Paternostro-Sluga, Tatjana; Vlychou, Marianna; Friedrich, Klaus; Mamisch, Tallal Charles; Trattnig, Siegfried

2012-02-01

The purpose of our investigation was to compare quantitative T2 relaxation time measurement evaluation of lumbar intervertebral discs with morphological grading in young to middle-aged patients with low back pain, using a standardized region-of-interest evaluation approach. Three hundred thirty lumbar discs from 66 patients (mean age, 39 years) with low back pain were examined on a 3.0T MR unit. Sagittal T1-FSE, sagittal, coronal, and axial T2-weighted FSE for morphological MRI, as well as a multi-echo spin-echo sequence for T2 mapping, were performed. Morphologically, all discs were classified according to Pfirrmann et al. Equally sized rectangular regions of interest (ROIs) for the annulus fibrosus were selected anteriorly and posteriorly in the outermost 20% of the disc. The space between was defined as the nucleus pulposus. To assess the reproducibility of this evaluation, inter- and intraobserver statistics were performed. The Pfirrmann scoring of 330 discs showed the following results: grade I: six discs (1.8%); grade II: 189 (57.3%); grade III: 96 (29.1%); grade IV: 38 (11.5%); and grade V: one (0.3%). The mean T2 values (in milliseconds) for the anterior and the posterior annulus, and the nucleus pulposus for the respective Pfirrmann groups were: I: 57/30/239; II: 44/67/129; III: 42/51/82; and IV: 42/44/56. The nucleus pulposus T2 values showed a stepwise decrease from Pfirrmann grade I to IV. The posterior annulus showed the highest T2 values in Pfirrmann group II, while the anterior annulus showed relatively constant T2 values in all Pfirrmann groups. The inter- and intraobserver analysis yielded intraclass correlation coefficients (ICC) for average measures in a range from 0.82 (anterior annulus) to 0.99 (nucleus). Our standardized method of region-specific quantitative T2 relaxation time evaluation seems to be able to characterize different degrees of disc degeneration quantitatively. The reproducibility of our ROI measurements is sufficient to encourage the use of this method in future investigations, particularly for longitudinal studies. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

[Biomechanical analysis on the correlation between iliac rotation displacement and L(4,5) disc degeneration].

PubMed

Shi, Ning-ning; Shen, Guo-quan; He, Shui-yong; Guo, Ru-bao

2016-05-01

To study the biomechanical relationship between iliac rotation displacement and L(4,5) disc degeneration, and to provide clinical evidences for the prevention and treatment of L(4,5) disc degeneration and herniation. From March 2012 to February 2014,68 patients with lumbar disc herniation combined with sacroiliac joint disorders were selected. Among them, 42 patients with L(4,5) disc herniation combined with sacroiliac joint disorders included 22 males and 20 females, ranging in age from 19 to 63 years old, with an average of (51.78 +/- 20.18) years old, and the duration of the disease ranged from 1 to 126 months with an average of (11.18 +/- 9.23) months. Twenty-six patients with L5S1 disc herniation combined with sacroiliac joint disorders included 11 males and 15 females, ranging in age from18 to 65 years old with an average of (45.53 +/- 27.23) years old, and the duration of the disease ranged from 0.5 to 103 months with an average of (11.99 +/- 12.56) months. Sixty-eight anteroposterior lumbar radiographs, 68 lateral lumbar radiographs,and 68 pelvic plain films were taken. The degree of lumbar scoliosis, pelvic tilt,and disc thickness were measured. The correlation between pelvic tilt and lumbar scoliosis ,lumbar scoliosis and disc thickness were studied by using linear and regression methods. The hiomechanical analysis was performed. There was a positive correlation between pelvic tilt and lumbar scoliosis in patients with L(4,5) disk herniation (R=0.49, P=0.00). There was a causal relationship and good linear proportional relationship (Y=3.05+1.07X, P=0.00) in the two variables. There was a negative correlation between lumbar scoliosis and intervertebral space in male patients with L (4,5) disk herniation (R = -0.50, P=0.01). There was a causal relationship and good linear proportional relationship in the two variables (Y=13.09-0.27X, P=0.02). But there was a positive correlation between lumbar scoliosis and intervertebral space in male patients with L5S1 disk herniation (R=0.46, P=0.04). Iliac rotational displacement are closely related with L(4,5) disc degeneration and herniation in biomechanics. A new concepts and therapeutic approach is provided for clinical treatment of chronic and refractory herniation of L(4,5) disc in patients

Total disc replacement using a tissue-engineered intervertebral disc in vivo: new animal model and initial results

PubMed Central

Gebhard, Harry; Bowles, Robby; Dyke, Jonathan; Saleh, Tatianna; Doty, Stephen; Bonassar, Lawrence; Härtl, Roger

2010-01-01

Study type: Basic science Introduction: Chronic back pain due to degenerative disc disease (DDD) is among the most important medical conditions causing morbidity and significant health care costs. Surgical treatment options include disc replacement or fusion surgery, but are associated with significant short- and long-term risks.1 Biological tissue-engineering of human intervertebral discs (IVD) could offer an important alternative.2 Recent in vitro data from our group have shown successful engineering and growth of ovine intervertebral disc composites with circumferentially aligned collagen fibrils in the annulus fibrosus (AF) (Figure 1).3 Figure 1 Tissue-engineered composite disc a Experimental steps to generate composite tissue-engineered IVDs3 b Example of different AF formulations on collagen alignment in the AF. Second harmonic generation and two-photon excited fluorescence images of seeded collagen gels (for AF) of 1 and 2.5 mg/ml over time. At seeding, cells and collagen were homogenously distributed in the gels. Over time, AF cells elongated and collagen aligned parallel to cells. Less contraction and less alignment is noted after 3 days in the 2.5 mg/mL gel. c Imaging-based creation of a virtual disc model that will serve as template for the engineered disc. Total disc dimensions (AF and NP) were retrieved from micro-computer tomography (CT) (left images), and nucleus pulposus (NP) dimensions alone were retrieved from T2-weighted MRI images (right images). Merging of MRI and micro-CT models revealed a composite disc model (middle image)—Software: Microview, GE Healthcare Inc., Princeton, NJ; and slicOmatic v4.3, TomoVision, Montreal, Canada. d Flow chart describing the process for generating multi-lamellar tissue engineered IVDs. IVDs are produced by allowing cell-seeded collagen layers to contract around a cell-seeded alginate core (NP) over time Objective: The next step is to investigate if biological disc implants survive, integrate, and restore function to the spine in vivo. A model will be developed that allows efficient in vivo testing of tissue-engineered discs of various compositions and characteristics. Methods: Athymic rats were anesthetized and a dorsal approach was chosen to perform a microsurgical discectomy in the rat caudal spine (Fig. 2,Fig. 3). Control group I (n = 6) underwent discectomy only, Control group II (n = 6) underwent discectomy, followed by reimplantation of the autologous disc. Two treatment groups (group III, n = 6, 1 month survival; group IV, n = 6, 6 months survival) received a tissue-engineered composite disc implant. The rodents were followed clinically for signs of infection, pain level and wound healing. X-rays and magnetic resonance imaging (MRI) were assessed postoperatively and up to 6 months after surgery (Fig. 6,Fig. 7). A 7 Tesla MRI (Bruker) was implemented for assessment of the operated level as well as the adjacent disc (hydration). T2-weighted sequences were interpreted by a semiquantitative score (0 = no signal, 1 = weak signal, 2 = strong signal and anatomical features of a normal disc). Histology was performed with staining for proteoglycans (Alcian blue) and collagen (Picrosirius red) (Fig. 4,Fig. 5). Figure 2 Disc replacement surgery a Operative situs with native disc that has been disassociated from both adjacent vertebrae b Native disc (left) and tissue-engineered implant (right) c Implant in situ before wound closureAF: Annulus fi brosus, nP: nucleus pulposus, eP: endplate, M: Muscle, T: Tendon, s: skin, art: artery, GP: Growth plate, B: Bone Figure 3 Disc replacement surgery. Anatomy of the rat caudal disc space a Pircrosirius red stained axial cut of native disc space b Saffranin-O stained sagittal cut of native disc space Figure 4 Histologies of three separate motion segments from three different rats. Animal one = native IVD, Animal two = status after discectomy, Animal three = tissue-engineered implant (1 month) a–c H&E (overall tissue staining for light micrsocopy) d–f Alcian blue (proteoglycans) g–i Picrosirius red (collagen I and II) Figure 5 Histology from one motion segment four months after implantation of a bio-engineered disc construct a Picrosirius red staining (collagen) b Polarized light microscopy showing collagen staining and collagen organization in AF region c Increased Safranin-O staining (proteoglycans) in NP region of the disc implant d Higher magnification of figure 5c: Integration between implanted tissue-engineered total disc replacement and vertebral body bone Figure 6 MRI a Disc space height measurements in flash/T1 sequence (top: implant (714.0 micrometer), bottom: native disc (823.5 micrometer) b T2 sequence, red circle surrounding the implant NP Figure 7 7 Tesla MRI imaging of rat tail IVDs showing axial images (preliminary pilot data) a Diffusion tensor imaging (DTI) on two explanted rat tail discs in Formalin b Higher magnification of a, showing directional alignment of collagen fibers (red and green) when compared to the color ball on top which maps fibers' directional alignment (eg, fibers directing from left to right: red, from top to bottom: blue) c Native IVD in vivo (successful imaging of top and bottom of the IVD (red) d Gradient echo sequence (GE) showing differentiation between NP (light grey) and AF (dark margin) e GE of reimplanted tail IVD at the explantation level f T1Rho sequence demonstrating the NP (grey) within the AF (dark margin), containing the yellow marked region of interest for value acquisition (preliminary data are consistent with values reported in the literature). g T2 image of native IVD in vivo for monitoring of hydration (white: NP) Results: The model allowed reproducible and complete discectomies as well as disc implantation in the rat tail spine without any surgical or postoperative complications. Discectomy resulted in immediate collapse of the disc space. Preliminary results indicate that disc space height was maintained after disc implantation in groups II, III and IV over time. MRI revealed high resolution images of normal intervertebral discs in vivo. Eight out of twelve animals (groups III and IV) showed a positive signal in T2-weighted images after 1 month (grade 0 = 4, grade 1 = 4, grade 2 = 4). Positive staining was seen for collagen as well as proteoglycans at the site of disc implantation after 1 month in each of the six animals with engineered implants (group III). Analysis of group IV showed positive T2 signal in five out of six animals and disc-height preservation in all animals after 6 months. Conclusions: This study demonstrates for the first time that tissue-engineered composite IVDs with circumferentially aligned collagen fibrils survive and integrate with surrounding vertebral bodies when placed in the rat spine for up to 6 months. Tissue-engineered composite IVDs restored function to the rat spine as indicated by maintenance of disc height and vertebral alignment. A significant finding was that maintenance of the composite structure in group III was observed, with increased proteoglycan staining in the nucleus pulposus region (Figure 4d–f). Proteoglycan and collagen matrix as well as disc height preservation and positive T2 signals in MRI are promising parameters and indicate functionality of the implants. PMID:23637671

Total disc replacement using a tissue-engineered intervertebral disc in vivo: new animal model and initial results.

PubMed

Gebhard, Harry; Bowles, Robby; Dyke, Jonathan; Saleh, Tatianna; Doty, Stephen; Bonassar, Lawrence; Härtl, Roger

2010-08-01

 Basic science Introduction:  Chronic back pain due to degenerative disc disease (DDD) is among the most important medical conditions causing morbidity and significant health care costs. Surgical treatment options include disc replacement or fusion surgery, but are associated with significant short- and long-term risks.1 Biological tissue-engineering of human intervertebral discs (IVD) could offer an important alternative.2 Recent in vitro data from our group have shown successful engineering and growth of ovine intervertebral disc composites with circumferentially aligned collagen fibrils in the annulus fibrosus (AF) (Figure 1).3 Figure 1 Tissue-engineered composite disc a Experimental steps to generate composite tissue-engineered IVDs3b Example of different AF formulations on collagen alignment in the AF. Second harmonic generation and two-photon excited fluorescence images of seeded collagen gels (for AF) of 1 and 2.5 mg/ml over time. At seeding, cells and collagen were homogenously distributed in the gels. Over time, AF cells elongated and collagen aligned parallel to cells. Less contraction and less alignment is noted after 3 days in the 2.5 mg/mL gel. c Imaging-based creation of a virtual disc model that will serve as template for the engineered disc. Total disc dimensions (AF and NP) were retrieved from micro-computer tomography (CT) (left images), and nucleus pulposus (NP) dimensions alone were retrieved from T2-weighted MRI images (right images). Merging of MRI and micro-CT models revealed a composite disc model (middle image)-Software: Microview, GE Healthcare Inc., Princeton, NJ; and slicOmatic v4.3, TomoVision, Montreal, Canada. d Flow chart describing the process for generating multi-lamellar tissue engineered IVDs. IVDs are produced by allowing cell-seeded collagen layers to contract around a cell-seeded alginate core (NP) over time Objective:  The next step is to investigate if biological disc implants survive, integrate, and restore function to the spine in vivo. A model will be developed that allows efficient in vivo testing of tissue-engineered discs of various compositions and characteristics.  Athymic rats were anesthetized and a dorsal approach was chosen to perform a microsurgical discectomy in the rat caudal spine (Fig. 2,Fig. 3). Control group I (n = 6) underwent discectomy only, Control group II (n = 6) underwent discectomy, followed by reimplantation of the autologous disc. Two treatment groups (group III, n = 6, 1 month survival; group IV, n = 6, 6 months survival) received a tissue-engineered composite disc implant. The rodents were followed clinically for signs of infection, pain level and wound healing. X-rays and magnetic resonance imaging (MRI) were assessed postoperatively and up to 6 months after surgery (Fig. 6,Fig. 7). A 7 Tesla MRI (Bruker) was implemented for assessment of the operated level as well as the adjacent disc (hydration). T2-weighted sequences were interpreted by a semiquantitative score (0 = no signal, 1 = weak signal, 2 = strong signal and anatomical features of a normal disc). Histology was performed with staining for proteoglycans (Alcian blue) and collagen (Picrosirius red) (Fig. 4,Fig. 5). Figure 2 Disc replacement surgery a Operative situs with native disc that has been disassociated from both adjacent vertebrae b Native disc (left) and tissue-engineered implant (right) c Implant in situ before wound closureAF: Annulus fi brosus, nP: nucleus pulposus, eP: endplate, M: Muscle, T: Tendon, s: skin, art: artery, GP: Growth plate, B: BoneFigure 3 Disc replacement surgery. Anatomy of the rat caudal disc space a Pircrosirius red stained axial cut of native disc space b Saffranin-O stained sagittal cut of native disc spaceFigure 4 Histologies of three separate motion segments from three different rats. Animal one = native IVD, Animal two = status after discectomy, Animal three = tissue-engineered implant (1 month) a-c H&E (overall tissue staining for light micrsocopy) d-f Alcian blue (proteoglycans) g-i Picrosirius red (collagen I and II)Figure 5 Histology from one motion segment four months after implantation of a bio-engineered disc construct a Picrosirius red staining (collagen) b Polarized light microscopy showing collagen staining and collagen organization in AF region c Increased Safranin-O staining (proteoglycans) in NP region of the disc implant d Higher magnification of figure 5c: Integration between implanted tissue-engineered total disc replacement and vertebral body boneFigure 6 MRI a Disc space height measurements in flash/T1 sequence (top: implant (714.0 micrometer), bottom: native disc (823.5 micrometer) b T2 sequence, red circle surrounding the implant NPFigure 7 7 Tesla MRI imaging of rat tail IVDs showing axial images (preliminary pilot data) a Diffusion tensor imaging (DTI) on two explanted rat tail discs in Formalin b Higher magnification of a, showing directional alignment of collagen fibers (red and green) when compared to the color ball on top which maps fibers' directional alignment (eg, fibers directing from left to right: red, from top to bottom: blue) c Native IVD in vivo (successful imaging of top and bottom of the IVD (red) d Gradient echo sequence (GE) showing differentiation between NP (light grey) and AF (dark margin) e GE of reimplanted tail IVD at the explantation level f T1Rho sequence demonstrating the NP (grey) within the AF (dark margin), containing the yellow marked region of interest for value acquisition (preliminary data are consistent with values reported in the literature). g T2 image of native IVD in vivo for monitoring of hydration (white: NP) Results:  The model allowed reproducible and complete discectomies as well as disc implantation in the rat tail spine without any surgical or postoperative complications. Discectomy resulted in immediate collapse of the disc space. Preliminary results indicate that disc space height was maintained after disc implantation in groups II, III and IV over time. MRI revealed high resolution images of normal intervertebral discs in vivo. Eight out of twelve animals (groups III and IV) showed a positive signal in T2-weighted images after 1 month (grade 0 = 4, grade 1 = 4, grade 2 = 4). Positive staining was seen for collagen as well as proteoglycans at the site of disc implantation after 1 month in each of the six animals with engineered implants (group III). Analysis of group IV showed positive T2 signal in five out of six animals and disc-height preservation in all animals after 6 months.  This study demonstrates for the first time that tissue-engineered composite IVDs with circumferentially aligned collagen fibrils survive and integrate with surrounding vertebral bodies when placed in the rat spine for up to 6 months. Tissue-engineered composite IVDs restored function to the rat spine as indicated by maintenance of disc height and vertebral alignment. A significant finding was that maintenance of the composite structure in group III was observed, with increased proteoglycan staining in the nucleus pulposus region (Figure 4d-f). Proteoglycan and collagen matrix as well as disc height preservation and positive T2 signals in MRI are promising parameters and indicate functionality of the implants.

Evaluation of Lumbar Intervertebral Disc Degeneration Using T1ρ and T2 Magnetic Resonance Imaging in a Rabbit Disc Injury Model.

PubMed

Ishikawa, Tetsuhiro; Watanabe, Atsuya; Kamoda, Hiroto; Miyagi, Masayuki; Inoue, Gen; Takahashi, Kazuhisa; Ohtori, Seiji

2018-04-01

An in vivo histologic and magnetic resonance imaging (MRI) study of lumbar intervertebral disc (IVD) degeneration was conducted. To clarify the sensitivity and efficacy of T1ρ/T2 mapping for IVD degeneration, the correlation between T1ρ/T2 mapping and degenerative grades and histological findings in the lumbar IVD were investigated. The early signs of IVD degeneration are proteoglycan loss, dehydration, and collagen degradation. Recently, several quantitative MRI techniques have been developed; T2 mapping can be used to evaluate hydration and collagen fiber integrity within cartilaginous tissue, and T1ρ mapping can be used to evaluate hydration and proteoglycan content. Using New Zealand White rabbits, annular punctures of the IVD were made 10 times at L2/3, 5 times at L3/4, and one time at L4/5 using an 18-gauge needle (n=6) or a 21-gauge needle (n=6). At 4 and 8 weeks post-surgery, MRI was performed including T1ρ and T2 mapping. The degree of IVD degeneration was macroscopically assessed using the Thompson grading system. All specimens were cut for hematoxylin and eosin, safranin-O, and toluidine blue staining. Disc degeneration became more severe as the number of punctures increased and when the larger needle was used. T1ρ and T2 values were significantly different between grade 1 and grade 3 IVDs, grade 1 and grade 4 IVDs, grade 2 and grade 3 IVDs, and grade 2 and grade 4 IVDs ( p <0.05). There was a significant difference between grade 1 and grade 2 IVDs only in terms of T1ρ values ( p <0.05). T1ρ and T2 quantitative MRI could detect these small differences. Our results suggest that T1ρ and T2 mapping are sensitive to degenerative changes of lumbar IVDs and that T1ρ mapping can be used as a clinical tool to identify early IVD degeneration.

The use of polyurethane materials in the surgery of the spine: a review.

PubMed

St John, Kenneth R

2014-12-01

The spine contains intervertebral discs and the interspinous and longitudinal ligaments. These structures are elastomeric or viscoelastic in their mechanical properties and serve to allow and control the movement of the bony elements of the spine. The use of metallic or hard polymeric devices to replace the intervertebral discs and the creation of fusion masses to replace discs and/or vertebral bodies changes the load transfer characteristics of the spine and the range of motion of segments of the spine. The purpose of the study was to survey the literature, regulatory information available on the Web, and industry-reported device development found on the Web to ascertain the usage and outcomes of the use of polyurethane polymers in the design and clinical use of devices for spine surgery. A systematic review of the available information from all sources concerning the subject materials' usage in spinal devices was conducted. A search of the peer-reviewed literature combining spinal surgery with polyurethane or specific types and trade names of medical polyurethanes was performed. Additionally, information available on the Food and Drug Administration Web site and for corporate Web sites was reviewed in an attempt to identify pertinent information. The review captured devices that are in testing or have entered clinical practice that use elastomeric polyurethane polymers as disc replacements, dynamic stabilization of spinal movement, or motion limitation to relieve nerve root compression and pain and as complete a listing as possible of such devices that have been designed or tested but appear to no longer be pursued. This review summarizes the available information about the uses to which polyurethanes have been tested or are being used in spinal surgery. The use of polyurethanes in medicine has expanded as modifications to the stability of the polymers in the physiological environment have been improved. The potential for the use of elastomeric materials to more closely match the mechanical properties of the structures being replaced and to maintain motion between spinal segments appears to hold promise. The published results from the use of the devices that are discussed show early success with these applications of elastomeric materials. Copyright © 2014 Elsevier Inc. All rights reserved.

Energy metabolism of intervertebral disc under mechanical loading.

PubMed

Wang, Chong; Gonzales, Silvia; Levene, Howard; Gu, Weiyong; Huang, Chun-Yuh Charles

2013-11-01

Intervertebral disc (IVD) degeneration is closely associated with low back pain (LBP), which is a major health concern in the U.S. Cellular biosynthesis of extracellular matrix (ECM), which is important for maintaining tissue integrity and preventing tissue degeneration, is an energy demanding process. Due to impaired nutrient support in avascular IVD, adenosine triphosphate (ATP) supply could be a limiting factor for maintaining normal ECM synthesis. Therefore, the objective of this study was to investigate the energy metabolism in the annulus fibrosus (AF) and nucleus pulposus (NP) of porcine IVD under static and dynamic compressions. Under compression, pH decreased and the contents of lactate and ATP increased significantly in both AF and NP regions, suggesting that compression can promote ATP production via glycolysis and reduce pH by increasing lactate accumulation. A high level of extracellular ATP content was detected in the NP region and regulated by compressive loading. Since ATP can serve not only as an intra-cellular energy currency, but also as a regulator of a variety of cellular activities extracellularly through the purinergic signaling pathway, our findings suggest that compression-mediated ATP metabolism could be a novel mechanobiological pathway for regulating IVD metabolism. © 2013 Orthopaedic Research Society.

Agreement between T2 and haste sequences in the evaluation of thoracolumbar intervertebral disc disease in dogs.

PubMed

Mankin, Joseph M; Hecht, Silke; Thomas, William B

2012-01-01

The purpose of this study was to compare half-Fourier-acquisition single-shot turbo spin-echo (HASTE) and T2-weighted (T2-W) sequences in dogs with thoracolumbar disc extrusion. MRI studies in 60 dogs (767 individual intervertebral disc spaces) were evaluated. Agreement between T2-W and HASTE sequences was assessed for two criteria: presence of an extradural lesion and treatment recommendation. There was moderate agreement between T2-W and HASTE sequences as to presence of an extradural lesion (kappa = 0.575). HASTE was in agreement in 96.1% of the sites where no extradural lesion was identified on T2-W images, but only in 58.1% of the sites where extradural lesions were identified on T2-W images. There was also moderate agreement between T2-W and HASTE sequences as to treatment recommendations (kappa = 0.476). HASTE was in agreement in 98.4% of the sites where a lesion was considered nonsurgical on T2 but only 82.1% of sites a lesion was considered surgical on T2. In 1.0% of sites considered not surgical and in 9.8% of sites considered equivocal based on T2-W images, a surgical lesion was identified on HASTE. Acquisition of a HASTE sequence in addition to conventional sequences may be beneficial in determining the severity of spinal cord compression in some cases when evaluating the canine spine.

Evaluation of the biological response of wear debris.

PubMed

Chang, Bong-Soon; Brown, Phillip Rand; Sieber, Ann; Valdevit, Antonio; Tateno, Kei; Kostuik, John Philip

2004-01-01

An animal study was conducted to evaluate the biological response to titanium particles from an artificial intervertebral disc in terms of serology and histologic changes. To determine the biological response to wear debris in the retroperitoneal and epidural space. Few wear studies exist about mechanical artificial discs. Twenty-three New Zealand white rabbits were used for two approaches of the lumbar spine. In a retroperitoneal group (10 rabbits), lateral flank approach at the L2-L3 area was used. In an epidural group (13 rabbits), a dorsal laminotomy of L2 was performed. The wear debris was obtained from mechanical test cycling of the implantable intervertebral disc. At 4 and 12 weeks postoperatively, five or six animals from each group were killed. The tissues, including deposition site, regional lymph nodes and major organs, were evaluated with hematoxylin and eosin staining. At death all rabbits were found to be healthy. Blood results from the predeath samples were found to be consistent with the preoperative blood work values. Scar tissue was minimal with good healing. All organs were found to be normal in appearance. On histopathology sections, adverse reactions such as fibrosis, granuloma formation or necrosis were not found in any tissues. Free particles were found sparingly in all tissue sections with minimal cellular response. No remarkable difference was found according to groups or time intervals. Smaller particles were found to be engulfed in macrophages without adverse biological consequences. Titanium particles traveled from the sites of deposition but elicited no to minimal biological response.

A novel finite element model of the ovine lumbar intervertebral disc with anisotropic hyperelastic material properties

PubMed Central

Galbusera, Fabio; Jonas, René; Schlager, Benedikt; Wilke, Hans-Joachim; Villa, Tomaso

2017-01-01

The Ovine spine is an accepted model to investigate the biomechanical behaviour of the human lumbar one. Indeed, the use of animal models for in vitro studies is necessary to investigate the mechanical behaviour of biological tissue, but needs to be reduced for ethical and social reasons. The aim of this study was to create a finite element model of the lumbar intervertebral disc of the sheep that may help to refine the understanding of parallel in vitro experiments and that can be used to predict when mechanical failure occurs. Anisotropic hyperelastic material properties were assigned to the annulus fibrosus and factorial optimization analyses were performed to find out the optimal parameters of the ground substance and of the collagen fibers. For the ground substance of the annulus fibrosus the investigation was based on experimental data taken from the literature, while for the collagen fibers tensile tests on annulus specimens were conducted. Flexibility analysis in flexion-extension, lateral bending and axial rotation were conducted. Different material properties for the anterior, lateral and posterior regions of the annulus were found. The posterior part resulted the stiffest region in compression whereas the anterior one the stiffest region in tension. Since the flexibility outcomes were in a good agreement with the literature data, we considered this model suitable to be used in conjunction with in vitro and in vivo tests to investigate the mechanical behaviour of the ovine lumbar disc. PMID:28472100

Biologic canine and human intervertebral disc repair by notochordal cell-derived matrix: from bench towards bedside.

PubMed

Bach, Frances C; Tellegen, Anna R; Beukers, Martijn; Miranda-Bedate, Alberto; Teunissen, Michelle; de Jong, Willem A M; de Vries, Stefan A H; Creemers, Laura B; Benz, Karin; Meij, Björn P; Ito, Keita; Tryfonidou, Marianna A

2018-05-29

The socioeconomic burden of chronic back pain related to intervertebral disc (IVD) disease is high and current treatments are only symptomatic. Minimally invasive strategies that promote biological IVD repair should address this unmet need. Notochordal cells (NCs) are replaced by chondrocyte-like cells (CLCs) during IVD maturation and degeneration. The regenerative potential of NC-secreted substances on CLCs and mesenchymal stromal cells (MSCs) has already been demonstrated. However, identification of these substances remains elusive. Innovatively, this study exploits the regenerative NC potential by using healthy porcine NC-derived matrix (NCM) and employs the dog as a clinically relevant translational model. NCM increased the glycosaminoglycan and DNA content of human and canine CLC aggregates and facilitated chondrogenic differentiation of canine MSCs in vitro . Based on these results, NCM, MSCs and NCM+MSCs were injected in mildly (spontaneously) and moderately (induced) degenerated canine IVDs in vivo and, after six months of treatment, were analyzed. NCM injected in moderately (induced) degenerated canine IVDs exerted beneficial effects at the macroscopic and MRI level, induced collagen type II-rich extracellular matrix production, improved the disc height, and ameliorated local inflammation. MSCs exerted no (additive) effects. In conclusion, NCM induced in vivo regenerative effects on degenerated canine IVDs. NCM may, comparable to demineralized bone matrix in bone regeneration, serve as 'instructive matrix', by locally releasing growth factors and facilitating tissue repair. Therefore, intradiscal NCM injection could be a promising regenerative treatment for IVD disease, circumventing the cumbersome identification of bioactive NC-secreted substances.

Plasma vitamin D and osteo-cartilaginous markers in Italian males affected by intervertebral disc degeneration: Focus on seasonal and pathological trend of type II collagen degradation.

PubMed

Brayda-Bruno, Marco; Viganò, Marco; Cauci, Sabina; Vitale, Jacopo A; de Girolamo, Laura; De Luca, Paola; Lombardi, Giovanni; Banfi, Giuseppe; Colombini, Alessandra

2017-08-01

To evaluate plasma vitamin D and cross-linked C-telopeptides of type I (CTx-I) and type II (CTx-II) collagen concentrations in males with lumbar intervertebral disc degeneration (IVD) compared to healthy controls. Improved knowledge might suggest to optimize the vitamin D status of IVD patients and contribute to clarify mechanisms of cartilage degradation. 79 Italian males with lumbar IVD assessed by Magnetic Resonance Imaging (MRI) and 79 age, sex and BMI-matched healthy controls were enrolled. Plasma 25hydroxyvitamin D (25(OH)D), CTx-I and CTx-II were measured by immunoassays. Circannual seasonality, correlation between biomarkers concentrations and clinical variables were assessed. Overall subjects 25(OH)D and CTx-II showed month rhythmicity with acrophase in August/September and October/November, and nadir in February/March and April/May, respectively. An inverse correlation between 25(OH)D and CTx-I, and a direct correlation between CTx-II and CTx-I were observed. IVD patients, particularly with osteochondrosis, showed higher CTx-II than healthy controls. Month of sampling may affect plasma 25(OH)D and CTx-II concentrations. The correlation between CTx-I and CTx-II suggests an interplay between the osteo-cartilaginous endplate and the fibro-cartilaginous disc. The results of this study highlighted that osteochondrosis associates with increased cartilaginous catabolism. Vitamin D supplementation seems more necessary in winter for lumbar IVD patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Lactoferricin mediates anabolic and anti-catabolic effects in the intervertebral disc.

PubMed

Kim, Jae-Sung; Ellman, Michael B; An, Howard S; Yan, Dongyao; van Wijnen, Andre J; Murphy, Gillian; Hoskin, David W; Im, Hee-Jeong

2012-04-01

Lactoferricin (LfcinB) antagonizes biological effects mediated by angiogenic and catabolic growth factors, in addition to pro-inflammatory cytokines and chemokines in human endothelial cells and tumor cells. However, the effect of LfcinB on intervertebral disc (IVD) cell metabolism has not yet been investigated. Using bovine nucleus pulposus (NP) cells, we analyzed the effect of LfcinB on proteoglycan (PG) accumulation, PG synthesis, and anabolic gene expression. We assessed expression of genes for matrix-degrading enzymes such as matrix metalloproteases (MMPs) and a disintegrin-like and metalloprotease with thrombospondin motifs (ADAMTS family), as well as their endogenous inhibitors, tissue inhibitor of metalloproteases (TIMPs). In order to understand the specific molecular mechanisms by which LfcinB exerts its biological effects, we investigated intracellular signaling pathways in NP cells. LfcinB increased PG accumulation mainly via PG synthesis in a dose-dependent manner. Simultaneously, LfcinB dose-dependently downregulated catabolic enzymes. LfcinB's anti-catabolic effects were further demonstrated by a dose-dependent increase in multiple TIMP family members. Our results demonstrate that ERK and/or p38 mitogen-activated protein kinase pathways are the key signaling cascades that exert the biological effects of LfcinB in NP cells, regulating transcription of aggrecan, SOX-9, TIMP-1, TIMP-2, TIMP-3, and iNOS. Our results suggest that LfcinB has anabolic and potent anti-catabolic biological effects on bovine IVD cells that may have considerable promise in the treatment of disc degeneration in the future. Copyright © 2011 Wiley Periodicals, Inc.

Engineering functional anisotropy in fibrocartilage neotissues.

PubMed

MacBarb, Regina F; Chen, Alison L; Hu, Jerry C; Athanasiou, Kyriacos A

2013-12-01

The knee meniscus, intervertebral disc, and temporomandibular joint (TMJ) disc all possess complex geometric shapes and anisotropic matrix organization. While these characteristics are imperative for proper tissue function, they are seldom recapitulated following injury or disease. Thus, this study's objective was to engineer fibrocartilages that capture both gross and molecular structural features of native tissues. Self-assembled TMJ discs were selected as the model system, as the disc exhibits a unique biconcave shape and functional anisotropy. To drive anisotropy, 50:50 co-cultures of meniscus cells and articular chondrocytes were grown in biconcave, TMJ-shaped molds and treated with two exogenous stimuli: biomechanical (BM) stimulation via passive axial compression and bioactive agent (BA) stimulation via chondroitinase-ABC and transforming growth factor-β1. BM + BA synergistically increased Col/WW, Young's modulus, and ultimate tensile strength 5.8-fold, 14.7-fold, and 13.8-fold that of controls, respectively; it also promoted collagen fibril alignment akin to native tissue. Finite element analysis found BM stimulation to create direction-dependent strains within the neotissue, suggesting shape plays an essential role toward driving in vitro anisotropic neotissue development. Methods used in this study offer insight on the ability to achieve physiologic anisotropy in biomaterials through the strategic application of spatial, biomechanical, and biochemical cues. Copyright © 2013 Elsevier Ltd. All rights reserved.

Engineering Functional Anisotropy in Fibrocartilage Neotissues

PubMed Central

MacBarb, R.F.; Chen, A.L.; Hu, J.C.; Athanasiou, K.A.

2013-01-01

The knee meniscus, intervertebral disc, and temporomandibular joint (TMJ) disc all possess complex geometric shapes and anisotropic matrix organization. While these characteristics are imperative for proper tissue function, they are seldom recapitulated following injury or disease. Thus, this study’s objective was to engineer fibrocartilages that capture both gross and molecular structural features of native tissues. Self-assembled TMJ discs were selected as the model system, as the disc exhibits a unique biconcave shape and functional anisotropy. To drive anisotropy, 50:50 co-cultures of meniscus cells and articular chondrocytes were grown in biconcave, TMJ-shaped molds and treated with two exogenous stimuli: biomechanical (BM) stimulation via passive axial compression and bioactive agent (BA) stimulation via chondroitinase-ABC and transforming growth factor-β1. BM+BA synergistically increased Col/WW, Young’s modulus, and ultimate tensile strength 5.8-fold, 14.7-fold, and 13.8-fold that of controls, respectively; it also promoted collagen fibril alignment akin to native tissue. Finite element analysis found BM stimulation to create direction-dependent strains within the neotissue, suggesting shape plays an essential role toward driving in vitro anisotropic neotissue development. Methods used in this study offer insight on the ability to achieve physiologic anisotropy in biomaterials through the strategic application of spatial, biomechanical, and biochemical cues. PMID:24075479

Biomechanical testing simulation of a cadaver spine specimen: development and evaluation study.

PubMed

Ahn, Hyung Soo; DiAngelo, Denis J

2007-05-15

This article describes a computer model of the cadaver cervical spine specimen and virtual biomechanical testing. To develop a graphics-oriented, multibody model of a cadaver cervical spine and to build a virtual laboratory simulator for the biomechanical testing using physics-based dynamic simulation techniques. Physics-based computer simulations apply the laws of physics to solid bodies with defined material properties. This technique can be used to create a virtual simulator for the biomechanical testing of a human cadaver spine. An accurate virtual model and simulation would complement tissue-based in vitro studies by providing a consistent test bed with minimal variability and by reducing cost. The geometry of cervical vertebrae was created from computed tomography images. Joints linking adjacent vertebrae were modeled as a triple-joint complex, comprised of intervertebral disc joints in the anterior region, 2 facet joints in the posterior region, and the surrounding ligament structure. A virtual laboratory simulation of an in vitro testing protocol was performed to evaluate the model responses during flexion, extension, and lateral bending. For kinematic evaluation, the rotation of motion segment unit, coupling behaviors, and 3-dimensional helical axes of motion were analyzed. The simulation results were in correlation with the findings of in vitro tests and published data. For kinetic evaluation, the forces of the intervertebral discs and facet joints of each segment were determined and visually animated. This methodology produced a realistic visualization of in vitro experiment, and allowed for the analyses of the kinematics and kinetics of the cadaver cervical spine. With graphical illustrations and animation features, this modeling technique has provided vivid and intuitive information.

Correlation between hypersensitivity to parenteral chymopapain and the presence of IgE anti-chymopapain antibody.

PubMed Central

Kapsalis, A A; Stern, I J; Bornstein, I

1978-01-01

A solid phase radioimmunoassay, similar to the RAST, was developed in an attempt to predict anaphylactic reactions in patients injected with the proteolytic enzyme chymopapain, used in therapy for prolapsed intervertebral disc. The test measured the serum content of anti-chymopapain antibodies of the IgE class. Of 1263 patients tested, twelve gave anaphylactic reactions. The test was predictive for seven of them (58%), while sixty were false positives. Measurements were also made of anti-chymopapain IgE or other classes of antibodies which developed in the sera of patients after chymopapain injection. The presence of antibodies to chymopapain in individuals who had not been injected was also demonstrated. PMID:709910

An update of the appraisal of the accuracy and utility of cervical discography in chronic neck pain.

PubMed

Onyewu, Obi; Manchikanti, Laxmaiah; Falco, Frank J E; Singh, Vijay; Geffert, Stephanie; Helm, Standiford; Cohen, Steven P; Hirsch, Joshua A

2012-01-01

Chronic neck pain represents a significant public health problem. Despite high prevalence rates, there is a lack of consensus regarding the causes or treatments for this condition. Based on controlled evaluations, the cervical intervertebral discs, facet joints, and atlantoaxial joints have all been implicated as pain generators. Cervical provocation discography, which includes disc stimulation and morphological evaluation, is occasionally used to distinguish a painful disc from other potential sources of pain. Yet in the absence of validation and controlled outcome studies, the procedure remains mired in controversy. A systematic review of the diagnostic accuracy of cervical discography. To systematically evaluate and update the diagnostic accuracy of cervical discography. The available literature on cervical discography was reviewed. Methodological quality assessment of included studies was performed using Quality Appraisal of Reliability Studies (QAREL). Only diagnostic accuracy studies meeting at least 50% of the designated inclusion criteria were utilized for analysis. However, studies scoring less than 50% are presented descriptively and analyzed critically. The level of evidence was classified as good, fair, and limited or poor based on the quality of evidence developed by the U.S. Preventive Services Task Force (USPSTF).Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 to June 2012, and manual searches of the bibliographies of known primary and review articles. A total of 41 manuscripts were considered for accuracy and utility of cervical discography in chronic neck pain. There were 23 studies evaluating accuracy of discography. There were 3 studies meeting inclusion criteria for assessing the accuracy and prevalence of discography, with a prevalence of 16% to 53%. Based on modified Agency for Healthcare Research and Quality (AHRQ) accuracy evaluation and United States Preventive Services Task Force (USPSTF) level of evidence criteria, this systematic review indicates the strength of evidence is limited for the diagnostic accuracy of cervical discography. Limitations include a paucity of literature, poor methodological quality, and very few studies performed utilizing International Association for the Study of Pain (IASP) criteria. There is limited evidence for the diagnostic accuracy of cervical discography. Nevertheless, in the absence of any other means to establish a relationship between pathology and symptoms, cervical provocation discography may be an important evaluation tool in certain contexts to identify a subset of patients with chronic neck pain secondary to intervertebral disc disorders. Based on the current systematic review, cervical provocation discography performed according to the IASP criteria with control disc(s), and a minimum provoked pain intensity of 7 of 10, or at least 70% reproduction of worst pain (i.e. worst spontaneous pain of 7 = 7 x 70% = 5), may be a useful tool for evaluating chronic pain and cervical disc abnormalities in a small proportion of patients.

Clinical classification in low back pain: best-evidence diagnostic rules based on systematic reviews.

PubMed

Petersen, Tom; Laslett, Mark; Juhl, Carsten

2017-05-12

Clinical examination findings are used in primary care to give an initial diagnosis to patients with low back pain and related leg symptoms. The purpose of this study was to develop best evidence Clinical Diagnostic Rules (CDR] for the identification of the most common patho-anatomical disorders in the lumbar spine; i.e. intervertebral discs, sacroiliac joints, facet joints, bone, muscles, nerve roots, muscles, peripheral nerve tissue, and central nervous system sensitization. A sensitive electronic search strategy using MEDLINE, EMBASE and CINAHL databases was combined with hand searching and citation tracking to identify eligible studies. Criteria for inclusion were: persons with low back pain with or without related leg symptoms, history or physical examination findings suitable for use in primary care, comparison with acceptable reference standards, and statistical reporting permitting calculation of diagnostic value. Quality assessments were made independently by two reviewers using the Quality Assessment of Diagnostic Accuracy Studies tool. Clinical examination findings that were investigated by at least two studies were included and results that met our predefined threshold of positive likelihood ratio ≥ 2 or negative likelihood ratio ≤ 0.5 were considered for the CDR. Sixty-four studies satisfied our eligible criteria. We were able to construct promising CDRs for symptomatic intervertebral disc, sacroiliac joint, spondylolisthesis, disc herniation with nerve root involvement, and spinal stenosis. Single clinical test appear not to be as useful as clusters of tests that are more closely in line with clinical decision making. This is the first comprehensive systematic review of diagnostic accuracy studies that evaluate clinical examination findings for their ability to identify the most common patho-anatomical disorders in the lumbar spine. In some diagnostic categories we have sufficient evidence to recommend a CDR. In others, we have only preliminary evidence that needs testing in future studies. Most findings were tested in secondary or tertiary care. Thus, the accuracy of the findings in a primary care setting has yet to be confirmed.

Percutaneous endoscopic lumbar discectomy via contralateral approach: a technical case report.

PubMed

Kim, Jin-Sung; Choi, Gun; Lee, Sang-Ho

2011-08-01

Technical case report. The authors report a new percutaneous endoscopic lumbar discectomy (PELD) technique for the treatment of lumbar disc herniation via a contralateral approach. When there are highly down-migrated lumbar disc herniation along just medial to pedicle and narrow ipsilateral intervertebral foramen, the conventional PELD is not easily accessible via ipsilateral transforaminal route. Five patients manifested gluteal and leg pain because of a soft disc herniation at the L4-L5 level. Transforaminal PELD via a contralateral approach was performed to remove the herniated fragment, achieving complete decompression of the nerve root. The symptom was relieved and the patient was discharged the next day. When a conventional transforaminal PELD is difficult because of some anatomical reasons, PELD via a contralateral route could be a good alternative option in selected cases.

Comparative Analysis of Ambulatory Morbidity in Four Patient Populations,

DTIC Science & Technology

1991-07-01

is most pronounced for females. Males in all study databases showed lower visit frequencies for sprains and strains of the sacroiliac (846) and...078), contact dermatitis (692), sprains and strains of the sacroiliac (846), bronchitis (490), intervertebral disc disorders (722), and inflammatory...and obesity (278). Similar to the USTF, males experienced lower visitfrequencies for contact dermatitis (692), sprains and strains of the sacroiliac

Biological treatment strategies for disc degeneration: potentials and shortcomings

PubMed Central

Nerlich, Andreas G.; Boos, Norbert

2006-01-01

Recent advances in molecular biology, cell biology and material sciences have opened a new emerging field of techniques for the treatment of musculoskeletal disorders. These new treatment modalities aim for biological repair of the affected tissues by introducing cell-based tissue replacements, genetic modifications of resident cells or a combination thereof. So far, these techniques have been successfully applied to various tissues such as bone and cartilage. However, application of these treatment modalities to cure intervertebral disc degeneration is in its very early stages and mostly limited to experimental studies in vitro or in animal studies. We will discuss the potential and possible shortcomings of current approaches to biologically cure disc degeneration by gene therapy or tissue engineering. Despite the increasing number of studies examining the therapeutic potential of biological treatment strategies, a practicable solution to routinely cure disc degeneration might not be available in the near future. However, knowledge gained from these attempts might be applied in a foreseeable future to cure the low back pain that often accompanies disc degeneration and therefore be beneficial for the patient. PMID:16983559

Degenerative changes of the canine cervical spine after discectomy procedures, an in vivo study.

PubMed

Grunert, Peter; Moriguchi, Yu; Grossbard, Brian P; Ricart Arbona, Rodolfo J; Bonassar, Lawrence J; Härtl, Roger

2017-06-23

Discectomies are a common surgical treatment for disc herniations in the canine spine. However, the effect of these procedures on intervertebral disc tissue is not fully understood. The objective of this study was to assess degenerative changes of cervical spinal segments undergoing discectomy procedures, in vivo. Discectomies led to a 60% drop in disc height and 24% drop in foraminal height. Segments did not fuse but showed osteophyte formation as well as endplate sclerosis. MR imaging revealed terminal degenerative changes with collapse of the disc space and loss of T2 signal intensity. The endplates showed degenerative type II Modic changes. Quantitative MR imaging revealed that over 95% of Nucleus Pulposus tissue was extracted and that the nuclear as well as overall disc hydration significantly decreased. Histology confirmed terminal degenerative changes with loss of NP tissue, loss of Annulus Fibrosus organization and loss of cartilage endplate tissue. The bony endplate displayed sclerotic changes. Discectomies lead to terminal degenerative changes. Therefore, these procedures should be indicated with caution specifically when performed for prophylactic purposes.

A narrative review of non-operative treatment, especially traditional Chinese medicine therapy, for lumbar intervertebral disc herniation.

PubMed

Zhang, Bo; Xu, Haidong; Wang, Juntao; Liu, Bin; Sun, Guodong

2017-01-01

Lumbar intervertebral disc herniation (LIDH), as the main contributor to low back pain and sciatica, imposes a heavy burden on both the individual and society. Non-operative treatment or conservative treatment has proven effective in alleviation of the symptoms of LIDH and are considered to be a first-line choice for most cases. Active lifestyle, physical therapy, complementary and alternative medicine therapy or Traditional Chinese medicine (TCM) therapy, and pharmacotherapy are routinely used as effective non-operative treatment for LIDH patients. However, how to choose one or several conservative treatments with higher efficacy, less side effects, minimal injury, and low cost is still a challenge for doctors and LIDH patients. Furthermore, there are some national characteristics for some conservative treatments in different countries, which bring difficulties for the widespread use of these methods. Here we initiated a search on the non-operative treatment especially TCM therapy for LIDH mainly using PubMed, Web of Science, China National Knowledge Internet (CNKI), and Chinese biomedicine database since the 1980s with no restriction of language. According to these related references, we gave a narrative review which emphasizes up-to-date knowledge regarding the effectiveness and safety of various conservative methods with special consideration for TCM therapy including acupuncture, autonomy, Chinese massage, and Chinese herbal medicines, for LIDH treatment. We hope this review will further contribute to an understanding of conservative treatment as an important choice for LIDH patients and provide useful information for the development of more effective conservative methods for LIDH treatment.

Effects of axial compression and rotation angle on torsional mechanical properties of bovine caudal discs.

PubMed

Bezci, Semih E; Klineberg, Eric O; O'Connell, Grace D

2018-01-01

The intervertebral disc is a complex joint that acts to support and transfer large multidirectional loads, including combinations of compression, tension, bending, and torsion. Direct comparison of disc torsion mechanics across studies has been difficult, due to differences in loading protocols. In particular, the lack of information on the combined effect of multiple parameters, including axial compressive preload and rotation angle, makes it difficult to discern whether disc torsion mechanics are sensitive to the variables used in the test protocol. Thus, the objective of this study was to evaluate compression-torsion mechanical behavior of healthy discs under a wide range of rotation angles. Bovine caudal discs were tested under a range of compressive preloads (150, 300, 600, and 900N) and rotation angles (± 1, 2, 3, 4, or 5°) applied at a rate of 0.5°/s. Torque-rotation data were used to characterize shape changes in the hysteresis loop and to calculate disc torsion mechanics. Torsional mechanical properties were described using multivariate regression models. The rate of change in torsional mechanical properties with compression depended on the maximum rotation angle applied, indicating a strong interaction between compressive stress and maximum rotation angle. The regression models reported here can be used to predict disc torsion mechanics under axial compression for a given disc geometry, compressive preload, and rotation angle. Copyright © 2017 Elsevier Ltd. All rights reserved.

Human disc degeneration is associated with increased MMP 7 expression.

PubMed

Le Maitre, C L; Freemont, A J; Hoyland, J A

2006-01-01

During intervertebral disc (IVD) degeneration, normal matrix synthesis decreases and degradation of disc matrix increases. A number of proteases that are increased during disc degeneration are thought to be involved in its pathogenesis. Matrix metalloproteinase 7 (MMP 7) (Matrilysin, PUMP-1) is known to cleave the major matrix molecules found within the IVD, i.e., the proteoglycan aggrecan and collagen type II. To date, however, it is not known how its expression changes with degeneration or its exact location. We investigated the localization of MMP 7 in human, histologically graded, nondegenerate, degenerated and prolapsed discs to ascertain whether MMP 7 is up-regulated during disc degeneration. Samples of human IVD tissue were fixed in neutral buffered formalin, embedded in paraffin, and sections stained with hematoxylin and eosin to score the degree of morphological degeneration. Immunohistochemistry was performed to localize MMP 7 in 41 human IVDs with varying degrees of degeneration. We found that the chondrocyte-like cells of the nucleus pulposus and inner annulus fibrosus were MMP 7 immunopositive; little immunopositivity was observed in the outer annulus. Nondegenerate discs showed few immunopositive cells. A significant increase in the proportion of MMP 7 immunopositive cells was seen in the nucleus pulposus of discs classified as showing intermediate levels of degeneration and a further increase was seen in discs with severe degeneration. Prolapsed discs showed more MMP 7 immunopositive cells compared to nondegenerated discs, but fewer than those seen in cases of severe degeneration.

Extradiscal ultrasound thermal therapy (ExDUSTT): evaluation in ex vivo and in vivo spine models (Invited Paper)

NASA Astrophysics Data System (ADS)

Diederich, Chris J.; Kinsey, Adam; Nau, William H.; Shu, Richard; Lotz, Jeffrey C.

2005-04-01

The application of heat to intervertebral discs is being clinically investigated for the treatment of discogenic back pain. The purpose of this study was to develop and test the feasibility of small ultrasound applicators that can be endoscopically placed adjacent to the disc, and deliver heating energy into the disc without puncturing the annular wall. Prototype devices were fabricated using curvilinear transducers (2.5-3.5 mm wide x 10 mm long, 5.4 - 6.5 MHz) that produce a narrow penetrating beam extending along the length of the ultrasound element. The transducer was affixed to either a flexible or rigid delivery catheter, and enclosed within an asymmetric coupling balloon with water-cooling flow. Bench measurements demonstrated 35-60% acoustic efficiencies, high-power output capabilities, and lightly focused beam patterns. The heating characteristics of these devices were evaluated with ex vivo and in vivo experiments within lumbar and cervical spine segments from sheep models and human cadaveric spine. The applicators were positioned adjacent to the annular wall of the surgically exposed discs. Ultrasound energy was focused directly into the disc to avoid heating the vertebral bodies. Multi-point thermocouple probes were placed throughout the disc to characterize the resultant temperature distributions. These studies demonstrated that ultrasound energy from these applicators penetrated the annular wall of the disc, and produced thermal coagulative temperatures of >60-65°C as far as 10 mm into the tissue. This study also showed that lower power levels and temperatures delivered for 10 minutes can generate a cytotoxic thermal dose of t43°C >240 min penetrating 5-10 mm from the annular wall.

Evaluation of intervertebral disc cartilaginous endplate structure using magnetic resonance imaging.

PubMed

Moon, Sung M; Yoder, Jonathon H; Wright, Alexander C; Smith, Lachlan J; Vresilovic, Edward J; Elliott, Dawn M

2013-08-01

The cartilaginous endplate (CEP) is a thin layer of hyaline cartilage positioned between the vertebral endplate and nucleus pulposus (NP) that functions both as a mechanical barrier and as a gateway for nutrient transport into the disc. Despite its critical role in disc nutrition and degeneration, the morphology of the CEP has not been well characterized. The objective of this study was to visualize and report observations of the CEP three-dimensional morphology, and quantify CEP thickness using an MRI FLASH (fast low-angle shot) pulse sequence. MR imaging of ex vivo human cadaveric lumbar spine segments (N = 17) was performed in a 7T MRI scanner with sequence parameters that were selected by utilizing high-resolution T1 mapping, and an analytical MRI signal model to optimize image contrast between CEP and NP. The CEP thickness at five locations along the mid-sagittal AP direction (center, 5 mm, 10 mm off-center towards anterior and posterior) was measured, and analyzed using two-way ANOVA and a post hoc Bonferonni test. For further investigation, six in vivo volunteers were imaged with a similar sequence in a 3T MRI scanner. In addition, decalcified and undecalcified histology was performed, which confirmed that the FLASH sequence successfully detected the CEP. CEP thickness determined by MRI in the mid-sagittal plane across all lumbar disc levels and locations was 0.77 ± 0.24 mm ex vivo. The CEP thickness was not different across disc levels, but was thinner toward the center of the disc. This study demonstrates the potential of MRI FLASH imaging for structural quantification of the CEP geometry, which may be developed as a technique to evaluate changes in the CEP with disc degeneration in future applications.

TGFβ and BMP Dependent Cell Fate Changes Due to Loss of Filamin B Produces Disc Degeneration and Progressive Vertebral Fusions

PubMed Central

Zieba, Jennifer; Forlenza, Kimberly Nicole; Khatra, Jagteshwar Singh; Sarukhanov, Anna; Duran, Ivan; Rigueur, Diana; Lyons, Karen M.; Cohn, Daniel H.; Merrill, Amy E.; Krakow, Deborah

2016-01-01

Spondylocarpotarsal synostosis (SCT) is an autosomal recessive disorder characterized by progressive vertebral fusions and caused by loss of function mutations in Filamin B (FLNB). FLNB acts as a signaling scaffold by linking the actin cytoskleteon to signal transduction systems, yet the disease mechanisms for SCT remain unclear. Employing a Flnb knockout mouse, we found morphologic and molecular evidence that the intervertebral discs (IVDs) of Flnb–/–mice undergo rapid and progressive degeneration during postnatal development as a result of abnormal cell fate changes in the IVD, particularly the annulus fibrosus (AF). In Flnb–/–mice, the AF cells lose their typical fibroblast-like characteristics and acquire the molecular and phenotypic signature of hypertrophic chondrocytes. This change is characterized by hallmarks of endochondral-like ossification including alterations in collagen matrix, expression of Collagen X, increased apoptosis, and inappropriate ossification of the disc tissue. We show that conversion of the AF cells into chondrocytes is coincident with upregulated TGFβ signaling via Smad2/3 and BMP induced p38 signaling as well as sustained activation of canonical and noncanonical target genes p21 and Ctgf. These findings indicate that FLNB is involved in attenuation of TGFβ/BMP signaling and influences AF cell fate. Furthermore, we demonstrate that the IVD disruptions in Flnb–/–mice resemble aging degenerative discs and reveal new insights into the molecular causes of vertebral fusions and disc degeneration. PMID:27019229

Organ culture bioreactors--platforms to study human intervertebral disc degeneration and regenerative therapy.

PubMed

Gantenbein, Benjamin; Illien-Jünger, Svenja; Chan, Samantha C W; Walser, Jochen; Haglund, Lisbet; Ferguson, Stephen J; Iatridis, James C; Grad, Sibylle

2015-01-01

In recent decades the application of bioreactors has revolutionized the concept of culturing tissues and organs that require mechanical loading. In intervertebral disc (IVD) research, collaborative efforts of biomedical engineering, biology and mechatronics have led to the innovation of new loading devices that can maintain viable IVD organ explants from large animals and human cadavers in precisely defined nutritional and mechanical environments over extended culture periods. Particularly in spine and IVD research, these organ culture models offer appealing alternatives, as large bipedal animal models with naturally occurring IVD degeneration and a genetic background similar to the human condition do not exist. Latest research has demonstrated important concepts including the potential of homing of mesenchymal stem cells to nutritionally or mechanically stressed IVDs, and the regenerative potential of "smart" biomaterials for nucleus pulposus or annulus fibrosus repair. In this review, we summarize the current knowledge about cell therapy, injection of cytokines and short peptides to rescue the degenerating IVD. We further stress that most bioreactor systems simplify the real in vivo conditions providing a useful proof of concept. Limitations are that certain aspects of the immune host response and pain assessments cannot be addressed with ex vivo systems. Coccygeal animal disc models are commonly used because of their availability and similarity to human IVDs. Although in vitro loading environments are not identical to the human in vivo situation, 3D ex vivo organ culture models of large animal coccygeal and human lumbar IVDs should be seen as valid alternatives for screening and feasibility testing to augment existing small animal, large animal, and human clinical trial experiments.

Biochemical validity of imaging techniques (X-ray, MRI, and dGEMRIC) in degenerative disc disease of the human cervical spine-an in vivo study.

PubMed

Bostelmann, Richard; Bostelmann, Tamara; Nasaca, Adrian; Steiger, Hans Jakob; Zaucke, Frank; Schleich, Christoph

2017-02-01

On a molecular level, maturation or degeneration of human intervertebral disc is among others expressed by the content of glycosaminoglycans (GAGs). According to the degenerative status, the disc content can differ in nucleus pulposus (NP) and annulus fibrosus (AF), respectively. Research in this area was conducted mostly on postmortem samples. Although several radiological classification systems exist, none includes biochemical features. Therefore, we focused our in vivo study on a widely spread and less expensive imaging technique for the cervical spine and the correlation of radiological patterns to biochemical equivalents in the intervertebral discs. The aim of this pilot study was to (1) measure the GAG content in human cervical discs, (2) to investigate whether a topographic biochemical GAG pattern can be found, and (3) whether there is a correlation between imaging data (X-ray and magnetic resonance imaging [MRI] including delayed gadolinium-enhanced MRI of cartilage [dGEMRIC] as a special imaging technique of cartilage) and the biochemical data. We conducted a prospective experimental pilot study. Only non-responders to conservative therapy were included. All subjects were physically and neurologically examined, and they completed their questionnaires. Visual analogue scale neck and arm, Neck Disability Index score, radiological parameters (X-rays, MRI, dGEMRIC), and the content of GAG in the cervical disc were assessed. After surgical removal of 12 discs, 96 fractions of AF and NP were biochemically analyzed for the GAG content using dimethylmethylene blue assay. A quantitative pattern of GAGs in the human cervical disc was identified. There were (1) significantly (p<.001) higher values of GAGs (µg GAG/mg tissue) in the NP (169.9 SD 37.3) compared with the AF (132.4 SD 42.2), and (2) significantly (p<.005) higher values of GAGs in the posterior (right/left: 149.9/160.2) compared with the anterior (right/left: 112.0/120.2) part of the AF. Third, we found in dGEMRIC imaging a significantly (p<.008) different distribution of GAGs in the cervical disc (NP 1083.3 ms [SD 248.6], AF 925.9 ms [SD 137.6]). Finally, we found that grading of disc degeneration in X-ray and MRI was significantly correlated with neither AF- nor NP-GAG content. The GAG content in human cervical discs can be detected in vivo and is subject to a significantly (p<.05) region-specific pattern (AF vs. NP; anterior vs. posterior in the AF). Up to the levels of AF and NP, this is reproducible in MRI in dGEMRIC technique, but not in X-ray or standard MRI sequences. Potentially, the MRI in dGEMRIC technique can be used as a non-invasive in vivo indicator for disc degeneration in the cervical spine. Copyright © 2016 Elsevier Inc. All rights reserved.

Multi-planar bending properties of lumbar intervertebral joints following cyclic bending.

PubMed

Chow, Daniel H K; Luk, Keith D K; Holmes, Andrew D; Li, Xing-Fei; Tam, Steven C W

2004-02-01

To assess the changes in the multi-planar bending properties of intervertebral joints following cyclic bending along different directions. An in vitro biomechanical study using porcine lumbar motion segments. Repeated bending has been suggested as part of the etiology of gradual prolapse of the intervertebral disc, but the multi-planar changes in bending properties following cyclic loading have not been examined in detail. Porcine lumbar motion segments were subject to 1500 cycles of bending along directions of 0 degrees (flexion), 30 degrees, 60 degrees, or 90 degrees (right lateral bending). The multi-planar bending moments and hysteresis energies were recorded before loading and after various cycle numbers. Repeated bending at 30 degrees and 60 degrees resulted in greater decreases in mean bending moment and hysteresis energy than bending at 0 degrees or 90 degrees. No significant differences were seen between loading groups for the change in bending moment along the anterior testing directions, but significant differences were observed in the posterior and lateral testing directions, with bending at 30 degrees causing a significantly greater decrease in bending moment in the postero-lateral directions. The change in mechanical properties of porcine intervertebral joints due to cyclic bending depend on the direction of loading and the direction in which the properties are measured. Loading at 30 degrees provokes the most marked changes in bending moment and hysteresis energy.

Sciatica caused by lumbar epidural gas.

PubMed

Belfquih, Hatim; El Mostarchid, Brahim; Akhaddar, Ali; gazzaz, Miloudi; Boucetta, Mohammed

2014-01-01

Gas production as a part of disc degeneration can occur but rarely causes nerve compression syndromes. The clinical features are similar to those of common sciatica. CT is very useful in the detection of epidural gas accumulation and nerve root compression. We report a case of symptomatic epidural gas accumulation originating from vacuum phenomenon in the intervertebral disc, causing lumbo-sacral radiculopathy. A 45-year-old woman suffered from sciatica for 9 months. The condition worsened in recent days. Computed tomography (CT) demonstrated intradiscal vacuum phenomenon, and accumulation of gas in the lumbar epidural space compressing the dural sac and S1 nerve root. After evacuation of the gas, her pain resolved without recurrence.

[Treatment of lumbar intervertebral disc herniation and sciatica with percutaneous transforaminal endoscopic technique].

PubMed

Jiang, Yi; Song, Hua-Wei; Wang, Dong; Yang, Ming-Lian

2013-10-01

To analyze the clinical effects of percutaneous transforaminal endoscopic technique in treating lumbar intervertebral disc herniation and sciatica. From June 2011 to January 2012,the clinical data of 46 patients with lumbar intervertebral disc herniation and sciatica underwent percutaneous transforaminal endoscopic technique were retrospectively analyzed. There were 28 males and 18 females,ranging in age from 11 to 77 years old with an average of (39.7_ 15.3) years old,20 cases were L5S1 and 26 cases were L4,5. All patients had the symptoms such as lumbago and sciatica and their straight-leg raising test were positive. Straight-leg raising test of patients were instantly repeated after operation;operative time,volume of blood loss,complication, length of stay and duration of back to work or daily life were recorded. The clinical effects were assessed according to the VAS,JOA and JOABPEQ score. All operations were successful,postoperative straight-leg raising test were all negative. Operative time,volume of blood loss,length of stay,duration of back to work or daily life,follow-up time were (93.0+/-28.0) min, (20.0+/-9.0)ml, (3.1+/-1.5) d, (11.6+/-4.2) d, (13.9+/-1.6) months,respectively. VAS score of lumbar before operation and at the 1st and 3rd,6th,12th month after operation were 5.3+/-1.2,1.9+/-1.1,1.0+/-0.8,0.9+/-0.8,0.8+/-0.6,respectively;VAS score of leg before operation and at the 1st and 3rd,6th,12th month after operation were 7.2+ 1.2,0.8+/-1.2,0.5+/-0.8,0.5+/-0.8,0.3+/-0.8,respectively. Five factors of JOABPEQ score,including lumbar pain,lumbar function, locomotor activity,social life viability and mental status,were respectively 27.0+/-30.6,37.3+/-27.4,38.5+/-26.6,33.0+/-13.7,55.4+/-19.0 before operation and 83.6+/-24.8,89.4+/-15.7,87.0+/-17.9,58.4+/-14.6,79.5+/-13.4 at final follow-up. Preoperative and postoperative JOA score were 9.1+/-2.6 and 27.3+/- 1.7, respectively. The postoperative VAS,JOA and JOABPEQ score had significantly improved (P<0.05). Percutaneous transforaminal endoscopic technique is safe and effective method in treating lumbar disc herniation and sciatica,it can fleetly relieve pain and the patient can recover daily life and work after treatment.

Aspergillus osteomyelitis of the spine.

PubMed

Govender, S; Rajoo, R; Goga, I E; Charles, R W

1991-07-01

Aspergillosis involving either the vertebral body or the intervertebral disc is a rare cause of osteomyelitis of the spine. The following is a report of five cases of Aspergillus fumigatus infection of the spine treated successfully with amphotericin B and 5-flucytosine. In three patients, the diagnosis was established at closed-needle biopsy; two patients with paraplegia had an anterior decompression and fusion. The follow-up period ranged from 19 to 48 months.

Spinal epidural abscess due to Aspergillus infection of the vertebrae: report of 3 cases.

PubMed

Dubbeld, P; van Oostenbrugge, R J; Twinjstra, A; Schouten, H C

1996-01-01

Aspergillus infection of the vertebral bodies and intervertebral disc spaces with consequent formation of a spinal epidural abscess was diagnosed in 3 patients with acute leukaemia. Medical therapy consisted of high-dose amphotericin-B with good local control of disease in one patient. The second patient underwent surgical drainage. The third patient had stabilisation of the disease. The clinical features, diagnosis and treatment are discussed.

Current Aeromedical Issues in Rotary Wing Operations.

DTIC Science & Technology

1999-08-01

normal lumbar lordosis (19). The spine losses the normal curve, the vertebral bodies tend to be closer together in front, and an increase in...a dorsally curved lumbar spine to the lumbar lordosis of his erect posture (Fig 1). From that transition comes his propensity to low back pain...flexibility of the lumbar spine relies upon the elasticity of the intervertebral discs. Fig 1. Change in lumbar lordosis with erect posture The

Evaluation and comparison of 3D intervertebral disc localization and segmentation methods for 3D T2 MR data: A grand challenge.

PubMed

Zheng, Guoyan; Chu, Chengwen; Belavý, Daniel L; Ibragimov, Bulat; Korez, Robert; Vrtovec, Tomaž; Hutt, Hugo; Everson, Richard; Meakin, Judith; Andrade, Isabel Lŏpez; Glocker, Ben; Chen, Hao; Dou, Qi; Heng, Pheng-Ann; Wang, Chunliang; Forsberg, Daniel; Neubert, Aleš; Fripp, Jurgen; Urschler, Martin; Stern, Darko; Wimmer, Maria; Novikov, Alexey A; Cheng, Hui; Armbrecht, Gabriele; Felsenberg, Dieter; Li, Shuo

2017-01-01

The evaluation of changes in Intervertebral Discs (IVDs) with 3D Magnetic Resonance (MR) Imaging (MRI) can be of interest for many clinical applications. This paper presents the evaluation of both IVD localization and IVD segmentation methods submitted to the Automatic 3D MRI IVD Localization and Segmentation challenge, held at the 2015 International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI2015) with an on-site competition. With the construction of a manually annotated reference data set composed of 25 3D T2-weighted MR images acquired from two different studies and the establishment of a standard validation framework, quantitative evaluation was performed to compare the results of methods submitted to the challenge. Experimental results show that overall the best localization method achieves a mean localization distance of 0.8 mm and the best segmentation method achieves a mean Dice of 91.8%, a mean average absolute distance of 1.1 mm and a mean Hausdorff distance of 4.3 mm, respectively. The strengths and drawbacks of each method are discussed, which provides insights into the performance of different IVD localization and segmentation methods. Copyright © 2016 Elsevier B.V. All rights reserved.

Reduction in nerve root compression by the nucleus pulposus after Feng's Spinal Manipulation☆

PubMed Central

Feng, Yu; Gao, Yan; Yang, Wendong; Feng, Tianyou

2013-01-01

Ninety-four patients with lumbar intervertebral disc herniation were enrolled in this study. Of these, 48 were treated with Feng's Spinal Manipulation, hot fomentation, and bed rest (treatment group). The remaining 46 patients were treated with hot fomentation and bed rest only (control group). After 3 weeks of treatment, clinical parameters including the angle of straight-leg raising, visual analogue scale pain score, and Japanese Orthopaedic Association score for low back pain were improved. The treatment group had significantly better improvement in scores than the control group. Magnetic resonance myelography three-dimensional reconstruction imaging of the vertebral canal demonstrated that filling of the compressed nerve root sleeve with cerebrospinal fluid increased significantly in the treatment group. The diameter of the nerve root sleeve was significantly larger in the treatment group than in the control group. However, the sagittal diameter index of the herniated nucleus pulposus and the angle between the nerve root sleeve and the thecal sac did not change significantly in either the treatment or control groups. The effectiveness of Feng's Spinal Manipulation for the treatment of symptoms associated with lumbar intervertebral disc herniation may be attributable to the relief of nerve root compression, without affecting the herniated nucleus pulposus or changing the morphology or position of the nerve root. PMID:25206408

Human umbilical cord mesenchymal stromal cells in regenerative medicine.

PubMed

Detamore, Michael S

2013-11-25

Cells of the human umbilical cord offer tremendous potential for improving human health. Cells from the Wharton’s jelly (umbilical cord stroma) in particular, referred to as human umbilical cord mesenchymal stromal cells (HUCMSCs), hold several advantages that make them appealing for translational research. In the previous issue of Stem Cell Research & Therapy, Chon and colleagues made an important contribution to the HUCMSC literature not only by presenting HUCMSCs as an emerging cell source for intervertebral disc regeneration in general and the nucleus pulposus in particular, but also by demonstrating that an extracellular matrix-based strategy might be preferred over the use of growth factors. By culturing HUCMSCs under hypoxia in serum-free conditions in the presence of Matrigel with laminin-111, they were able to achieve intense collagen II staining by 21 days without the addition of exogenous growth factors. There is tremendous translational significance here in that such raw materials may alleviate the need for the use of growth factors in some instances, and this may have important ramifications in reducing product cost and streamlining regulatory approval. Chon and colleagues provide a promising example of the potential of HUCMSCs, demonstrating the ability to guide HUCMSC differentiation even in the absence of serum and growth factors and supporting the use of HUCMSCs as a viable alternative in intervertebral disc regeneration.

Gallic acid inhibits the release of ADAMTS4 in nucleus pulposus cells by inhibiting p65 phosphorylation and acetylation of the NF-κB signaling pathway.

PubMed

Huang, Yao; Chen, Jian; Jiang, Tao; Zhou, Zheng; Lv, Bin; Yin, Guoyong; Fan, Jin

2017-07-18

This study investigated the inhibitory effect of gallic acid (GA) on the release of A Disintegrin and Metalloproteinase with Thrombospondin motifs 4 (ADAMTS4) through the regulation of the NF-κB signaling pathway, which is closely related to the matrix metalloproteinases in nucleus pulposus cells. Different concentrations of GA were added to TNF-α-induced human nucleus pulposus cells (hNPCs) and intervertebral disc degeneration rat model. ADAMTS-4 expression increased both in the TNF-α-induced nucleus pulposus cells and intervertebral disc degeneration rat model. By contrast, the release of ADAMTS-4 was reduced, and the TNF-α-induced apoptosis of nucleus pulposus cells was significantly inhibited after addition of GA at different concentrations. Further study found that the levels of phosphorylated p65 (p-p65) was increased and the classical NF-κB signal pathway was activated after the nucleus pulposus cells were stimulated by TNF-α. Meanwhile, GA suppressed the p65 phosphorylation and inceased p65 deacetylation levels. As a consequence, GA can decrease the expression of ADAMTS-4 in nucleus pulposus cells by regulating the phosphorylation and acetylation of p65 in NF-κB signaling pathways.

Estrogen receptors involvement in intervertebral discogenic pain of the elderly women: colocalization and correlation with the expression of Substance P in nucleus pulposus

PubMed Central

Li, Xin-Feng; Yu, Bu-Wei

2017-01-01

Estrogenic modulation of pain is an exceedingly complex phenomenon. However, whether estrogen is involved in discogenic low back pain still remains unclear. Here, immunoreactivity staining technique was used to examine the expression level of the estrogen receptors (ERα and ERβ) and a pain related neuropeptide, Substance P in the lumbar intervertebral discs to analyze the relationship between the ERs and Substance P. Nucleus pulposus tissues of 23 elderly female patients were harvested during spinal surgeries and made to detect the immunoreactivity staining of ERα, ERβ and Substance P. The colocalization and intensities of ERs and Substance P were explored and evaluated respectively. The correlations between changes of ERα, ERβ and Substance P were also assessed.Our results revealed that Substance P colocalized with ERα and ERβ both in cytoplasm and nucleus of the nucleus pulposus cells. HSCORE analysis indicated that Substance P negatively correlated with both ERα and ERβ expression. Collectively, the crosstalk between ERs and Substance P might exist in the disc tissue. Estrogen-dependent pain mechanism might partly be mediated through ERs and Substance P in the nucleus pulposus of the elderly females. Estrogen and its receptors might be drug targets in discogenic low back pain diseases. PMID:28430617

Estrogen receptors involvement in intervertebral discogenic pain of the elderly women: colocalization and correlation with the expression of Substance P in nucleus pulposus.

PubMed

Song, Xiao-Xing; Shi, Sheng; Guo, Zhen; Li, Xin-Feng; Yu, Bu-Wei

2017-06-13

Estrogenic modulation of pain is an exceedingly complex phenomenon. However, whether estrogen is involved in discogenic low back pain still remains unclear. Here, immunoreactivity staining technique was used to examine the expression level of the estrogen receptors (ERα and ERβ) and a pain related neuropeptide, Substance P in the lumbar intervertebral discs to analyze the relationship between the ERs and Substance P. Nucleus pulposus tissues of 23 elderly female patients were harvested during spinal surgeries and made to detect the immunoreactivity staining of ERα, ERβ and Substance P. The colocalization and intensities of ERs and Substance P were explored and evaluated respectively. The correlations between changes of ERα, ERβ and Substance P were also assessed.Our results revealed that Substance P colocalized with ERα and ERβ both in cytoplasm and nucleus of the nucleus pulposus cells. HSCORE analysis indicated that Substance P negatively correlated with both ERα and ERβ expression. Collectively, the crosstalk between ERs and Substance P might exist in the disc tissue. Estrogen-dependent pain mechanism might partly be mediated through ERs and Substance P in the nucleus pulposus of the elderly females. Estrogen and its receptors might be drug targets in discogenic low back pain diseases.

3D characterization of morphological changes in the intervertebral disc and endplate during aging: A propagation phase contrast synchrotron micro-tomography study

PubMed Central

Cao, Yong; Liao, Shenghui; Zeng, Hao; Ni, Shuangfei; Tintani, Francis; Hao, Yongqiang; Wang, Lei; Wu, Tianding; Lu, Hongbin; Duan, Chunyue; Hu, Jianzhong

2017-01-01

A better understanding of functional changes in the intervertebral disc (IVD) and interaction with endplate is essential to elucidate the pathogenesis of IVD degeneration disease (IDDD). To date, the simultaneous depiction of 3D micro-architectural changes of endplate with aging and interaction with IVD remains a technical challenge. We aim to characterize the 3D morphology changes of endplate and IVD during aging using PPCST. The lumbar vertebral level 4/5 IVDs harvested from 15-day-, 4- and 24-month-old mice were initially evaluated by PPCST with histological sections subsequently analyzed to confirm the imaging efficiency. Quantitative assessments of age-related trends after aging, including mean diameter, volume fraction and connectivity of the canals, and endplate porosity and thickness, reached a peak at 4 months and significantly decreased at 24 months. The IVD volume consistently exhibited same trend of variation with the endplate after aging. In this study, PPCST simultaneously provided comprehensive details of 3D morphological changes of the IVD and canal network in the endplate and the interaction after aging. The results suggest that PPCST has the potential to provide a new platform for attaining a deeper insight into the pathogenesis of IDDD, providing potential therapeutic targets. PMID:28266560

Early onset of disc degeneration in SM/J mice is associated with changes in ion transport systems and fibrotic events.

PubMed

Zhang, Ying; Xiong, Chi; Kudelko, Mateusz; Li, Yan; Wang, Cheng; Wong, Yuk Lun; Tam, Vivian; Rai, Muhammad Farooq; Cheverud, James; Lawson, Heather A; Sandell, Linda; Chan, Wilson C W; Cheah, Kathryn S E; Sham, Pak C; Chan, Danny

2018-04-09

Intervertebral disc degeneration (IDD) causes back pain and sciatica, affecting quality of life and resulting in high economic/social burden. The etiology of IDD is not well understood. Along with aging and environmental factors, genetic factors also influence the onset, progression and severity of IDD. Genetic studies of risk factors for IDD using human cohorts are limited by small sample size and low statistical power. Animal models amenable to genetic and functional studies of IDD provide desirable alternatives. Despite differences in size and cellular content as compared to human intervertebral discs (IVDs), the mouse is a powerful model for genetics and assessment of cellular changes relevant to human biology. Here, we provide evidence for early onset disc degeneration in SM/J relative to LG/J mice with poor and good tissue healing capacity respectively. In the first few months of life, LG/J mice maintain a relatively constant pool of notochordal-like cells in the nucleus pulposus (NP) of the IVD. In contrast, chondrogenic events are observed in SM/J mice beginning as early as one-week-old, with progressive fibrotic changes. Further, the extracellular matrix changes in the NP are consistent with IVD degeneration. Leveraging on the genomic data of two parental and two recombinant inbred lines, we assessed the genetic contribution to the NP changes and identified processes linked to the regulation of ion transport systems. Significantly, "transport" system is also in the top three gene ontology (GO) terms from a comparative proteomic analysis of the mouse NP. These findings support the potential of the SM/J, LG/J and their recombinant inbred lines for future genetic and biological analysis in mice and validation of candidate genes and biological relevance in human cohort studies. The proteomic data has been deposited to the ProteomeXchange Consortium via the PRIDE [1] partner repository with the dataset identifier PXD008784. Copyright © 2017. Published by Elsevier B.V.

Tumor Necrosis Factor-α– and Interleukin-1β–Dependent Matrix Metalloproteinase-3 Expression in Nucleus Pulposus Cells Requires Cooperative Signaling via Syndecan 4 and Mitogen-Activated Protein Kinase–NF-κB Axis

PubMed Central

Wang, Xin; Wang, Hua; Yang, Hao; Li, Jun; Cai, Qiqing; Shapiro, Irving M.; Risbud, Makarand V.

2015-01-01

Matrix metalloproteinase-3 (MMP-3) plays an important role in intervertebral disc degeneration, a ubiquitous condition closely linked to low back pain and disability. Elevated expression of syndecan 4, a cell surface heparan sulfate proteoglycan, actively controls disc matrix catabolism. However, the relationship between MMP-3 expression and syndecan 4 in the context of inflammatory disc disease has not been clearly defined. We investigated the mechanisms by which cytokines control MMP-3 expression in rat and human nucleus pulposus cells. Cytokine treatment increased MMP-3 expression and promoter activity. Stable silencing of syndecan 4 blocked cytokine-mediated MMP-3 expression; more important, syndecan 4 did not mediate its effects through NF-κB or mitogen-activated protein kinase (MAPK) pathways. However, treatment with MAPK and NF-κB inhibitors resulted in partial blocking of the inductive effect of cytokines on MMP-3 expression. Loss-of-function studies confirmed that NF-κB, p38α/β2/γ/δ, and extracellular signal–regulated kinase (ERK) 2, but not ERK1, contributed to cytokine-dependent induction of MMP3 promoter activity. Similarly, inhibitor treatments, lentiviral short hairpin-p65, and short hairpin-IκB kinase β significantly decreased cytokine-dependent up-regulation in MMP-3 expression. Finally, we show that transforming growth factor-β can block the up-regulation of MMP-3 induced by tumor necrosis factor (TNF)-α by counteracting the NF-κB pathway and syndecan 4 expression. Taken together, our results suggest that cooperative signaling through syndecan 4 and the TNF receptor 1–MAPK–NF-κB axis is required for TNF-α–dependent expression of MMP-3 in nucleus pulposus cells. Controlling these pathways may slow the progression of intervertebral disc degeneration and matrix catabolism. PMID:25063530

Effects of Different Angles of the Traction Table on Lumbar Spine Ligaments: A Finite Element Study.

PubMed

Farajpour, Hekmat; Jamshidi, Nima

2017-12-01

The traction bed is a noninvasive device for treating lower back pain caused by herniated intervertebral discs. In this study, we investigated the impact of the traction bed on the lower back as a means of increasing the disc height and creating a gap between facet joints. Computed tomography (CT) images were obtained from a female volunteer and a three-dimensional (3D) model was created using software package MIMICs 17.0. Afterwards, the 3D model was analyzed in an analytical software (Abaqus 6.14). The study was conducted under the following traction loads: 25%, 45%, 55%, and 85% of the whole body weight in different angles. Results indicated that the loading angle in the L3-4 area had 36.8%, 57.4%, 55.32%, 49.8%, and 52.15% effect on the anterior longitudinal ligament, posterior longitudinal ligament, intertransverse ligament, interspinous ligament, and supraspinous ligament, respectively. The respective values for the L4-5 area were 32.3%, 10.6%, 53.4%, 56.58%, and 57.35%. Also, the body weight had 63.2%, 42.6%, 44.68%, 50.2%, and 47.85% effect on the anterior longitudinal ligament, posterior longitudinal ligament, intertransverse ligament, interspinous ligament, and supraspinous ligament, respectively. The respective values for the L4-5 area were 67.7%, 89.4%, 46.6%, 43.42% and 42.65%. The authenticity of results was checked by comparing with the experimental data. The results show that traction beds are highly effective for disc movement and lower back pain relief. Also, an optimal angle for traction can be obtained in a 3D model analysis using CT or magnetic resonance imaging images. The optimal angle would be different for different patients and thus should be determined based on the decreased height of the intervertebral disc, weight and height of patients.

Improved display of cervical intervertebral discs on water (iodine) images: incidental findings from single-source dual-energy CT angiography of head and neck arteries.

PubMed

Wu, Qingxia; Shi, Dapeng; Cheng, Tianming; Liu, Hongming; Hu, Niuniu; Chang, Xiaowan; Guo, Ying; Wang, Meiyun

2018-06-19

To (a) assess the diagnostic performance of material decomposition (MD) water (iodine) images for the evaluation of cervical intervertebral discs (IVDs) in patients who underwent dual-energy head and neck CT angiography (HNCTA) compared with 70-keV images and (b) to explore the correlation of water concentration with the T2 relaxation time of IVDs. Twenty-four consecutive patients who underwent dual-energy HNCTA and cervical spine MRI were studied. The diagnostic performance of water (iodine), 70-keV and MR images for IVD bulge and herniation was assessed. A subjective image score for each image set was recorded. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of IVDs to the cervical spinal cord were compared between water (iodine) and 70-keV images. Disc water concentration as measured on water (iodine) images was correlated with T2 relaxation time. IVD evaluations for bulge and herniation did not differ significantly among the three image sets (pairwise comparisons; all p > 0.05). SNR and CNR were significantly improved on water (iodine) images compared with those on 70-keV images (p < 0.001). Although water (iodine) images showed higher image quality scores when evaluating IVDs compared with 70-keV images, the difference is not significant (all adjusted p > 0.05). IVD water concentration exhibited no correlation with relative T2 relaxation time (all p > 0.05). Water (iodine) images facilitated analysis of cervical IVDs by providing higher SNR and CNR compared with 70-keV images. The disc water concentration measured on water (iodine) images exhibited no correlation with relative T2 relaxation time. • There was no significant difference in cervical IVD evaluations for bulge and herniation among water (iodine) images, 70-keV images and MR images. • Water (iodine) images provided higher objective and subjective image quality than 70-keV images, though the difference of subjective evaluation was not statistically significant. • The disc water concentration exhibited no correlation with relative T2 relaxation time, which reflects the inferiority of the water (iodine) images in evaluating disc water content compared with T2 maps.

Expression and regulation of neurotrophins in the nondegenerate and degenerate human intervertebral disc

PubMed Central

Purmessur, Devina; Freemont, Anthony J; Hoyland, Judith A

2008-01-01

Introduction The neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have been identified in the human intervertebral disc (IVD) and have been implicated in the mechanisms associated with nerve ingrowth and nociception in degeneration of the IVD. The aim of the current study was to investigate an association between neurotrophin expression in the IVD and the severity of disc degeneration, including the effect of disc-related proinflammatory cytokines on neurotrophin and neuropeptide expression in cells derived from the human IVD. Methods Immunohistochemical analysis was performed to examine the expression of NGF, BDNF and their high-affinity receptors Trk-A and Trk-B in human IVD samples, divided into three categories: non-degenerate, moderate degeneration and severe degeneration. In order to study the effect of disc-related cytokines on neurotrophin/neuropeptide gene expression, nucleus pulposus cells derived from non-degenerate and degenerate IVD samples were seeded in alginate and were stimulated with either IL-1β or TNFα for 48 hours. RNA was extracted, cDNA was synthesised and quantitative real-time PCR was performed to examine the expression of NGF, BDNF and substance P. Results Immunohistochemistry showed expression of NGF and BDNF in the native chondrocyte-like cells in all regions of the IVD and in all grades of degeneration. Interestingly only BDNF significantly increased with the severity of degeneration (P < 0.05). Similar expression was observed for Trk-A and Trk-B, although no association with disease severity was demonstrated. In cultured human nucleus pulposus cells, stimulation with IL-1β led to significant increases in NGF and BDNF gene expression (P < 0.05). Treatment with TNFα was associated with an upregulation of substance P expression only. Conclusion Our findings show that both the annulus fibrosus and nucleus pulposus cells of the IVD express the neurotrophins NGF and BDNF, factors that may influence and enhance innervation and pain in the degenerate IVD. Expression of Trk-A and Trk-B by cells of the nondegenerate and degenerate IVD suggests an autocrine role for neurotrophins in regulation of disc cell biology. Furthermore, modulation of neurotrophin expression by IL-1β and modulation of substance P expression by TNFα, coupled with their increased expression in the degenerate IVD, highlights novel roles for these cytokines in regulating nerve ingrowth in the degenerate IVD and associated back pain. PMID:18727839

Genipin cross-linked type II collagen/chondroitin sulfate composite hydrogel-like cell delivery system induces differentiation of adipose-derived stem cells and regenerates degenerated nucleus pulposus.

PubMed

Zhou, Xiaopeng; Wang, Jingkai; Fang, Weijing; Tao, Yiqing; Zhao, Tengfei; Xia, Kaishun; Liang, Chengzhen; Hua, Jianming; Li, Fangcai; Chen, Qixin

2018-04-15

Nucleus pulposus (NP) degeneration is usually the origin of intervertebral disc degeneration and consequent lower back pain. Although adipose-derived stem cell (ADSC)-based therapy is regarded to be promising for the treatment of degenerated NP, there is a lack of viable cell carriers to transplant ADSCs into the NP while maintaining cell function. In this study, we developed a type II collagen/chondroitin sulfate (CS) composite hydrogel-like ADSC (CCSA) delivery system with genipin as the cross-linking agent. The induction effect of the scaffold on ADSC differentiation was studied in vitro, and a rat coccygeal vertebrae degeneration model was used to investigate the regenerative effect of the CCSA system on the degenerated NP in vivo. The results showed that the CCSA delivery system cross-linked with 0.02% genipin was biocompatible and promoted the expressions of NP-specific genes. After the injection of the CCSA system, the disc height, water content, extracellular matrix synthesis, and structure of the degenerated NP were partly restored. Our CCSA delivery system uses minimally invasive approaches to promote the regeneration of degenerated NP and provides an exciting new avenue for the treatment of degenerative disc disease. Nucleus pulposus (NP) degeneration is usually the origin of intervertebral disc degeneration and consequent lower back pain. Stem cell-based tissue engineering is a promising method in NP regeneration, but there is a lack of viable cell carriers to transplant ADSCs into the NP while maintaining cell function. In this study, we developed a type II collagen/chondroitin sulfate (CS) composite hydrogel-like ADSC (CCSA) delivery system with genipin as the cross-linking agent. Although several research groups have studied the fabrication of injectable hydrogel with biological matrix, our study differs from other works. We chose type II collagen and CS, the two primary native components in the NP, as the main materials and combined them according to the natural ratio of collagen and sGAG in the NP. The delivery system is preloaded with ADSCs and can be injected into the NP with a needle, followed by in situ gelation. Genipin is used as a cross-linker to improve the bio-stability of the scaffold, with low cytotoxicity. We investigated the stimulatory effects of our scaffold on the differentiation of ADSCs in vitro and the regenerative effect of the CCSA delivery system on degenerated NP in vivo. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Dynamic analysis of forces in the lumbar spine during bag carrying.

PubMed

Gómez, Lessby; Díaz, Carlos A; Orozco, Gustavo A; García, José J

2017-09-07

The intervertebral disc supports axial and shear forces generated during tasks such as lifting and carrying weights. The objective of this study was to determine the forces in the lumbar spine of workers carrying a bag on the head, on the shoulder and on the anterior part of the trunk. Kinematic measurements were recorded for 10 subjects carrying bags of 10, 20 and 25 kg on each of the three aforementioned positions. A simple dynamic model implemented in a custom program was then developed to determine the lumbar forces using the accelerations and positions obtained from the kinematic analysis. The analyses yielded a maximum compressive force of 2338.4 ± 422 N when a 25-kg bag was carried on the anterior part of the trunk. Carrying bags on the anterior part of the trunk generated higher lumbar forces compared to those developed by carrying the bag on the head or on the shoulder. Force levels suggest that this activity represents a moderate risk for the subjects. However, future biomechanical models should be developed to analyze the cumulative effect in the discs when longer periods of time are spent in this activity.

Facet joint geometry and intervertebral disk degeneration in the L5-S1 region of the vertebral column in German Shepherd dogs.

PubMed

Seiler, Gabriela S; Häni, Hansjürg; Busato, André R; Lang, Johann

2002-01-01

To evaluate the possible association between facet joint geometry and intervertebral disk degeneration in German Shepherd Dogs. 25 German Shepherd Dogs and 11 control dogs of similar body weight and condition. Facet joint angles in the caudal portion of the lumbar region of the vertebral column (L5-S1) were measured by use of computed tomography, and the intervertebral discs were evaluated microscopically. The relationship between facet joint geometry and disk degeneration was evaluated by use of statistical methods. German Shepherd Dogs had significantly more facet joint tropism than control dogs, but an association with disk degeneration was not found. However, German Shepherd Dogs had a different facet joint conformation, with more sagittally oriented facet joints at L5-L6 and L6-L7 and a larger angle difference between the lumbar and lumbosacral facet joints, compared with control dogs. A large difference between facet joint angles at L6-L7 and L7-S1 in German Shepherd Dogs may be associated with the frequent occurrence of lumbosacral disk degeneration in this breed.

Sensory innervation of the dorsal longitudinal ligament and the meninges in the lumbar spine of the dog.

PubMed

Waber-Wenger, Barbara; Forterre, Franck; Kuehni-Boghenbor, Kathrin; Danuser, Renzo; Stein, Jens Volker; Stoffel, Michael Hubert

2014-10-01

Although intervertebral disc herniation is a well-known disease in dogs, pain management for this condition has remained a challenge. The goal of the present study is to address the lack of information regarding the innervation of anatomical structures within the canine vertebral canal. Immunolabeling was performed with antibodies against protein gene product 9.5, Tuj-1 (neuron-specific class III β-tubulin), calcitonin gene-related peptide, and neuropeptide Y in combination with the lectin from Lycopersicon esculentum as a marker for blood vessels. Staining was indicative of both sensory and sympathetic fibers. Innervation density was the highest in lateral areas, intermediate in dorsal areas, and the lowest in ventral areas. In the dorsal longitudinal ligament (DLL), the highest innervation density was observed in the lateral regions. Innervation was lower at mid-vertebral levels than at intervertebral levels. The presence of sensory and sympathetic fibers in the canine dura and DLL suggests that pain may originate from both these structures. Due to these regional differences in sensory innervation patterns, trauma to intervertebral DLL and lateral dura is expected to be particularly painful. The results ought to provide a better basis for the assessment of medicinal and surgical procedures.

Medical Surveillance Monthly Report (MSMR). Volume 18, Number 05, May 2011

DTIC Science & Technology

2011-05-01

most ED visits – injuries and poisonings, signs and symptoms of ill-defi ned conditions, and respiratory diseases – were similar among military...176,066) were the most frequent specifi c diagnoses reported during injury/poisoning-related visits (data not shown). “Signs, symptoms , and ill...diagnosis overall (Table 2). “Other signs, symptoms and ill-defi ned conditions” and “spinal disorders” (which includes intervertebral disc Figure 1

Lumbar Facet Tropism: A Comprehensive Review.

PubMed

Alonso, Fernando; Kirkpatrick, Christina M; Jeong, William; Fisahn, Christian; Usman, Sameera; Rustagi, Tarush; Loukas, Marios; Chapman, Jens R; Oskouian, Rod J; Tubbs, R Shane

2017-06-01

Scattered reports exist in the medical literature regarding facet tropism. However, this finding has had mixed conclusions regarding its origin and impact on the normal spine. We performed a literature review of the anatomy, embryology, biomechanics, and pathology related to lumbar facet tropism. Facet tropism is most commonly found at L4-L5 vertebral segments and there is some evidence that this condition may lead to facet degenerative spondylolisthesis, intervertebral disc disease, and other degenerative conditions. Long-term analyses of patients are necessary to elucidate relationships between associated findings and facet tropism. In addition, a universally agreed definition that is more precise should be developed for future investigative studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Neurologic outcome after thoracolumbar partial lateral corpectomy for intervertebral disc disease in 72 dogs.

PubMed

Salger, Florian; Ziegler, Luisa; Böttcher, Irene Christine; Oechtering, Gerhard; Böttcher, Peter; Flegel, Thomas

2014-07-01

To determine neurologic outcome and factors influencing outcome after thoracolumbar partial lateral corpectomy (PLC) in dogs with intervertebral disc disease (IVDD) causing ventral spinal cord compression. Retrospective case series. Dogs with IVDD (n = 72; 87 PLC). Dogs with IVDD between T9 and L5 were included if treated by at least 1 PLC. Exclusion criteria were: previous spinal surgery, combination of PLC with another surgical procedure. Neurologic outcome was assessed by: (1) modified Frankel score (MFS) based on neurologic examinations at 4 time points (before surgery, immediately after PLC, at discharge and 4 weeks after PLC); and (2) owner questionnaire. The association of the following factors with neurologic outcome was analyzed: age, body weight, duration of current neurologic dysfunction (acute, chronic), IVDD localization, breed (chondrodystrophic, nonchondrodystrophic), number of PLCs, degree of presurgical spinal cord compression and postsurgical decompression, slot depth, presurgical MFS. Presurgical spinal cord compression was determined by CT myelography (71 dogs) or MRI (1 dog), whereas postsurgical decompression and slot depth were determined on CT myelography (69 dogs). MFS was improved in 18.7%, 31.7%, and 64.2% of dogs at the 3 postsurgical assessments, whereas it was unchanged in 62.6%, 52.8%, and 32.0% at corresponding time points. Based on owner questionnaire, 91.4% of dogs were ambulatory 6 months postsurgically with 74.5% having a normal gait. Most improvement in neurologic function developed within 6 months after surgery. Presurgical MFS was the only variable significantly associated with several neurologic outcome measurements (P < .01). PLC is an option for decompression in ventrally compressing thoracolumbar IVDD. Prognosis is associated with presurgical neurologic condition. © Copyright 2014 by The American College of Veterinary Surgeons.

Delivering growth factors through a polymeric scaffold to cell cultures containing both nucleus pulposus and annulus fibrosus.

PubMed

Akyuva, Yener; Kaplan, Necati; Yilmaz, Ibrahim; Ozbek, Hanefi; Sirin, Duygu Yasar; Karaaslan, Numan; Guler, Olcay; Ateş, Özkan

2018-04-09

The aim of this in vitro experimental study was to design a novel, polyvinyl alcohol(PVA)-basedpolymericscaffold that permits the controlled release of insulin-likegrowthfactor1(IGF-1)/bonemorphogenetic protein-2(BMP-2) following intervertebral disc administration. The drug delivery system was composed of two different solutions that formed a scaffold within seconds after coming into contact with each other. We performed swelling,pH,temperature tests and analysis of the controlled release of growth factors from this system.The release kinetics of the growth factors was determined through enzyme linked immunosorbent assay(ELISA). Cell proliferation and viability was monitored with microscopy and analyzed using an MTT assay and acridine orange/propidium iodide(AO/PI) staining. Chondroadherin(CHAD), hypoxiainduciblefactor-1alpha(HIF-1α),collagentypeII(COL2A1) gene expressions were determined with quantitative real-timepolymerasechainreaction(qRT-PCR) analysis to show the effects of IGF-1/BMP-2 administration on annulus fibrosus cell(AFC)/nucleus pulposus cell(NPC) cultures. The scaffold allowed for the controlled release of IGF-1 and BMP-2 in different time intervals. It was observed that as the application time increased, the number of cells and the degree of extracellular matrix development increased in AFC/NPC cultures. AO/PI staining and an MTT analysis showed that cells retained their specific morphology and continued to proliferate. It was observed that HIF-1α and CHAD expression increased in a time-dependent manner, and there wasn't any COL2A1 expression in the AFC/NPC cultures. The designed scaffold may be used as an alternative method for intervertebral disc administration of growth factors after further in vivo studies. We believe that such prototype scaffolds may be an innovative technology in targeted drug therapies after reconstructive neurosurgeries.

Vertebral pneumatocysts.

PubMed

Arslan, G; Ceken, K; Cubuk, M; Ozkaynak, C; Lüleci, E

2001-01-01

To review the prevalence and location of vertebral pneumatocysts and evaluate the CT findings of these benign lesions. Retrospectively we reviewed CT images of 89 patients with suspected disc disease during a 6-month period. Distinctive CT pattern of intraosseous pneumatocysts involving the cervical, thoracic and lumbar spine was found. In 8 patients (9%), 10 vertebral pneumatocysts were detected. Five were located in the vertebral body and 4 of these were associated with vacuum phenomenon in adjacent intervertebral discs. Five were located near the facet joint and all were associated with vacuum phenomenon in adjacent facet joint. Intraosseous pneumatocyst is a benign lesion, therefore biopsy and follow-up are unnecessary. Although vertebral pneumatocysts seem to be uncommon with a few reported cases, this study shows them to be more frequent than previously thought.

Role of chondroitin sulphate tethered silk scaffold in cartilaginous disc tissue regeneration.

PubMed

Bhattacharjee, Maumita; Chawla, Shikha; Chameettachal, Shibu; Murab, Sumit; Bhavesh, Neel Sarovar; Ghosh, Sourabh

2016-04-12

Strategies for tissue engineering focus on scaffolds with tunable structure and morphology as well as optimum surface chemistry to simulate the anatomy and functionality of the target tissue. Silk fibroin has demonstrated its potential in supporting cartilaginous tissue formation both in vitro and in vivo. In this study, we investigate the role of controlled lamellar organization and chemical composition of biofunctionalized silk scaffolds in replicating the structural properties of the annulus region of an intervertebral disc using articular chondrocytes. Covalent attachment of chondroitin sulfate (CS) to silk is characterized. CS-conjugated silk constructs demonstrate enhanced cellular metabolic activity and chondrogenic redifferentiation potential with significantly improved mechanical properties over silk-only constructs. A matrix-assisted laser desorption ionization-time of flight analysis and protein-protein interaction studies help to generate insights into how CS conjugation can facilitate the production of disc associated matrix proteins, compared to a silk-only based construct. An in-depth understanding of the interplay between such extra cellular matrix associated proteins should help in designing more rational scaffolds for cartilaginous disc regeneration needs.

A phenotypic comparison of intervertebral disc and articular cartilage cells in the rat

PubMed Central

Lee, Cynthia R.; Sakai, Daisuke; Nakai, Tomoko; Toyama, Kanae; Mochida, Joji; Alini, Mauro

2007-01-01

The basic molecular characteristics of intervertebral disc cells are still poorly defined. This study compared the phenotypes of nucleus pulposus (NP), annulus fibrosus (AF) and articular cartilage (AC) cells using rat coccygeal discs and AC from both young and aged animals and a combination of microarray, real-time RT-PCR and immunohistochemistry. Microarray analysis identified 63 genes with at least a fivefold difference in fluorescence intensity between the NP and AF cells and 41 genes with a fivefold or greater difference comparing NP cells and articular chondrocytes. In young rats, the relative mRNA levels, assessed by real-time RT-PCR, of annexin A3, glypican 3 (gpc3), keratin 19 (k19) and pleiotrophin (ptn) were significantly higher in NP compared to AF and AC samples. Furthermore, vimentin (vim) mRNA was higher in NP versus AC, and expression levels of cartilage oligomeric matrix protein (comp) and matrix gla protein (mgp) were lower in NP versus AC. Higher NP levels of comp and mgp mRNA and higher AF levels of gpc3, k19, mgp and ptn mRNA were found in aged compared to young tissue. However, the large differences between NP and AC expression of gpc3 and k19 were obvious even in the aged animals. Furthermore, the differences in expression levels of gpc3 and k19 were also evident at the protein level, with intense immunostaining for both proteins in NP and non-existent immunoreaction in AF and AC. Future studies using different species are required to evaluate whether the expression of these molecules can be used to characterize NP cells and distinguish them from other chondrocyte-like cells. PMID:17786487

Intervertebral disc-derived stem cells: implications for regenerative medicine and neural repair.

PubMed

Erwin, W Mark; Islam, Diana; Eftekarpour, Eftekhar; Inman, Robert D; Karim, Muhammad Zia; Fehlings, Michael G

2013-02-01

An in vitro and in vivo evaluation of intervertebral disc (IVD)-derived stem/progenitor cells. To determine the chondrogenic, adipogenic, osteogenic, and neurogenic differentiation capacity of disc-derived stem/progenitor cells in vitro and neurogenic differentiation in vivo. Tissue repair strategies require a source of appropriate cells that could be used to replace dead or damaged cells and tissues such as stem cells. Here we examined the potential use of IVD-derived stem cells in regenerative medicine approaches and neural repair. Nonchondrodystrophic canine IVD nucleus pulposus (NP) cells were used to generate stem/progenitor cells (NP progenitor cells [NPPCs]) and the NPPCs were differentiated in vitro into chondrogenic, adipogenic, and neurogenic lineages and in vivo into the neurogenic lineage. NPPCs were compared with bone marrow-derived mesenchymal (stromal) stem cells in terms of the expression of stemness genes. The expression of the neural crest marker protein 0 and the Brachyury gene were evaluated in NP cells and NPPCs. NPPCs contain stem/progenitor cells and express "stemness" genes such as Sox2, Oct3/4, Nanog, CD133, Nestin, and neural cell adhesion molecule but differ from mesenchymal (stromal) stem cells in the higher expression of the Nanog gene by NPPCs. NPPCs do not express protein 0 or the Brachyury gene both of which are expressed by the totality of IVD NP cells. The percentage of NPPCs within the IVD is 1% of the total as derived by colony-forming assay. NPPCs are capable of differentiating along chondrogenic, adipogenic, and neurogenic lineages in vitro and into oligodendrocyte, neuron, and astroglial specific precursor cells in vivo within the compact myelin-deficient shiverer mouse. We propose that the IVD NP represents a regenerative niche suggesting that the IVD could represent a readily accessible source of precursor cells for neural repair and regeneration.

Organ Culture Bioreactors – Platforms to Study Human Intervertebral Disc Degeneration and Regenerative Therapy

PubMed Central

Gantenbein, Benjamin; Illien-Jünger, Svenja; Chan, Samantha CW; Walser, Jochen; Haglund, Lisbet; Ferguson, Stephen J; Iatridis, James C; Grad, Sibylle

2015-01-01

In recent decades the application of bioreactors has revolutionized the concept of culturing tissues and organs that require mechanical loading. In intervertebral disc (IVD) research, collaborative efforts of biomedical engineering, biology and mechatronics have led to the innovation of new loading devices that can maintain viable IVD organ explants from large animals and human cadavers in precisely defined nutritional and mechanical environments over extended culture periods. Particularly in spine and IVD research, these organ culture models offer appealing alternatives, as large bipedal animal models with naturally occurring IVD degeneration and a genetic background similar to the human condition do not exist. Latest research has demonstrated important concepts including the potential of homing of mesenchymal stem cells to nutritionally or mechanically stressed IVDs, and the regenerative potential of “smart” biomaterials for nucleus pulposus or annulus fibrosus repair. In this review, we summarize the current knowledge about cell therapy, injection of cytokines and short peptides to rescue the degenerating IVD. We further stress that most bioreactor systems simplify the real in vivo conditions providing a useful proof of concept. Limitations are that certain aspects of the immune host response and pain assessments cannot be addressed with ex vivo systems. Coccygeal animal disc models are commonly used because of their availability and similarity to human IVDs. Although in vitro loading environments are not identical to the human in vivo situation, 3D ex vivo organ culture models of large animal coccygeal and human lumbar IVDs should be seen as valid alternatives for screening and feasibility testing to augment existing small animal, large animal, and human clinical trial experiments. PMID:25764196

The Pfirrmann classification of lumbar intervertebral disc degeneration: an independent inter- and intra-observer agreement assessment.

PubMed

Urrutia, Julio; Besa, Pablo; Campos, Mauricio; Cikutovic, Pablo; Cabezon, Mario; Molina, Marcelo; Cruz, Juan Pablo

2016-09-01

Grading inter-vertebral disc degeneration (IDD) is important in the evaluation of many degenerative conditions, including patients with low back pain. Magnetic resonance imaging (MRI) is considered the best imaging instrument to evaluate IDD. The Pfirrmann classification is commonly used to grade IDD; the authors describing this classification showed an adequate agreement using it; however, there has been a paucity of independent agreement studies using this grading system. The aim of this study was to perform an independent inter- and intra-observer agreement study using the Pfirrmann classification. T2-weighted sagittal images of 79 patients consecutively studied with lumbar spine MRI were classified using the Pfirrmann grading system by six evaluators (three spine surgeons and three radiologists). After a 6-week interval, the 79 cases were presented to the same evaluators in a random sequence for repeat evaluation. The intra-class correlation coefficient (ICC) and the weighted kappa (wκ) were used to determine the inter- and intra-observer agreement. The inter-observer agreement was excellent, with an ICC = 0.94 (0.93-0.95) and wκ = 0.83 (0.74-0.91). There were no differences between spine surgeons and radiologists. Likewise, there were no differences in agreement evaluating the different lumbar discs. Most differences among observers were only of one grade. Intra-observer agreement was also excellent with ICC = 0.86 (0.83-0.89) and wκ = 0.89 (0.85-0.93). In this independent study, the Pfirrmann classification demonstrated an adequate agreement among different observers and by the same observer on separate occasions. Furthermore, it allows communication between radiologists and spine surgeons.

Silk-based multilayered angle-ply annulus fibrosus construct to recapitulate form and function of the intervertebral disc.

PubMed

Bhunia, Bibhas K; Kaplan, David L; Mandal, Biman B

2018-01-16

Recapitulation of the form and function of complex tissue organization using appropriate biomaterials impacts success in tissue engineering endeavors. The annulus fibrosus (AF) represents a complex, multilamellar, hierarchical structure consisting of collagen, proteoglycans, and elastic fibers. To mimic the intricacy of AF anatomy, a silk protein-based multilayered, disc-like angle-ply construct was fabricated, consisting of concentric layers of lamellar sheets. Scanning electron microscopy and fluorescence image analysis revealed cross-aligned and lamellar characteristics of the construct, mimicking the native hierarchical architecture of the AF. Induction of secondary structure in the silk constructs was confirmed by infrared spectroscopy and X-ray diffraction. The constructs showed a compressive modulus of 499.18 ± 86.45 kPa. Constructs seeded with porcine AF cells and human mesenchymal stem cells (hMSCs) showed ∼2.2-fold and ∼1.7-fold increases in proliferation on day 14, respectively, compared with initial seeding. Biochemical analysis, histology, and immunohistochemistry results showed the deposition of AF-specific extracellular matrix (sulfated glycosaminoglycan and collagen type I), indicating a favorable environment for both cell types, which was further validated by the expression of AF tissue-specific genes. The constructs seeded with porcine AF cells showed ∼11-, ∼5.1-, and ∼6.7-fold increases in col I α 1 , sox 9, and aggrecan genes, respectively. The differentiation of hMSCs to AF-like tissue was evident from the enhanced expression of the AF-specific genes. Overall, the constructs supported cell proliferation, differentiation, and ECM deposition resulting in AF-like tissue features based on ECM deposition and morphology, indicating potential for future studies related to intervertebral disc replacement therapy.

Intervertebral disc degeneration-induced expression of pain-related molecules: glial cell-derived neurotropic factor as a key factor.

PubMed

Jung, Woon-Won; Kim, Hyun-Sook; Shon, Jong-Ryeul; Lee, Min; Lee, Sang-Heon; Sul, Donggeun; Na, Heung Sik; Kim, Joo Han; Kim, Byung-Jo

2011-10-01

Discogenic low back pain has been shown to develop into chronic intractable pain due to an unknown pathogenesis. To study the mechanism of discogenic pain, we analyzed the serial expression of pain-related molecules in the dorsal root ganglia (DRG) and thalamus using a newly developed rat model of disc degeneration. Ten microliters of complete Freund's adjuvant was injected into the L5-6 disc of male Sprague-Dawley rats for 10 minutes using a 26-gauge needle. Using a behavioral test, rats with significant pain were selected and subsequently serial gene expression of pain-related molecules in the DRG and the thalamus was analyzed by reverse transcriptase polymerase chain reaction. The expression of tumor necrosis factor-α and interleukin-1β significantly increased at 4 and 8 weeks in the DRG of rats with pain. Furthermore, interleukin-6 was significantly increased at 4 weeks in the DRG; however, these cytokines did not show a significant change in the thalamus. Calcitonin gene-related peptide and substance P were significantly increased in DRG at 4 and 8 weeks and in the thalamus at 2 and 4 weeks. The level of nerve growth factor-β did not significantly increase in the DRG or thalamus, whereas glial cell line-derived neurotropic factor (GDNF) was significantly increased at 2 weeks and was sustained through 8 weeks in both the DRG and thalamus. The disc degeneration rat model described herein led to significant pain of a chronic nature. The gradual and persistent increase of GDNF in both the thalamus and DRG suggests that GDNF might be a key factor in the development of intractable, chronic discogenic pain.

Intradiscal injection of simvastatin results in radiologic, histologic, and genetic evidence of disc regeneration in a rat model of degenerative disc disease

PubMed Central

Than, Khoi D.; Rahman, Shayan U.; Wang, Lin; Khan, Adam; Kyere, Kwaku A.; Than, Tracey T.; Miyata, Yoshinari; Park, Yoon-Shin; La Marca, Frank; Kim, Hyungjin M.; Zhang, Huina; Park, Paul; Lin, Chia-Ying

2014-01-01

BACKGROUND CONTEXT A large percentage of back pain can be attributed to degeneration of the intervertebral disc (IVD). Bone morphogenetic protein-2 (BMP-2) is known to play an important role in chondrogenesis of the IVD. Simvastatin is known to up-regulate expression of BMP-2. Thus, we hypothesized that intradiscal injection of simvastatin in a rat model of degenerative disc disease (DDD) would result in retardation of DDD. PURPOSE To develop a novel conservative treatment for DDD and related discogenic back pain. STUDY DESIGN/SETTING Laboratory investigation. METHODS Disc injury was induced in 272 rats via 21-gauge needle puncture. After 6 weeks, injured discs were treated with simvastatin in a saline or hydrogel carrier. Rats were sacrificed at predetermined time points. Outcome measures assessed were radiologic, histologic, and genetic. Radiologically, the MRI index (number of pixels multiplied by corresponding image densities) was determined. Histologically, disc spaces were read by 3 blinded scorers employing a previously described histological grading scale. Genetically, nuclei pulposi were harvested and polymerase chain reaction was run to determine relative levels of aggrecan, collagen type II, and BMP-2 gene expression. This project was supported by Grant No. R01 AR056649 from NIAMS/NIH. There are no other financial conflicts of interest to report. RESULTS Radiologically, discs treated with 5 mg/mL simvastatin in hydrogel or saline demonstrated MRI indices that were normal through 8 weeks post-treatment, although this was more sustained when delivered in hydrogel. Histologically, discs treated with 5 mg/mL simvastatin in hydrogel demonstrated improved grades in comparison to discs treated at higher doses. Genetically, discs treated with 5 mg/mL of simvastatin in hydrogel demonstrated higher gene expression of aggrecan and collagen type II than control. CONCLUSIONS Degenerate discs treated with 5 mg/mL simvastatin in a hydrogel carrier demonstrated radiographic and histologic features resembling normal, non-injured IVDs. In addition, gene expression of aggrecan and collagen type II (important constituents of the IVD extracellular matrix) was up-regulated in treated discs. Injection of simvastatin into degenerate IVDs may result in retardation of disc degeneration and represents a promising investigational therapy for conservative treatment of DDD. PMID:24291703

Application of the polynomial chaos expansion to approximate the homogenised response of the intervertebral disc.

PubMed

Karajan, N; Otto, D; Oladyshkin, S; Ehlers, W

2014-10-01

A possibility to simulate the mechanical behaviour of the human spine is given by modelling the stiffer structures, i.e. the vertebrae, as a discrete multi-body system (MBS), whereas the softer connecting tissue, i.e. the softer intervertebral discs (IVD), is represented in a continuum-mechanical sense using the finite-element method (FEM). From a modelling point of view, the mechanical behaviour of the IVD can be included into the MBS in two different ways. They can either be computed online in a so-called co-simulation of a MBS and a FEM or offline in a pre-computation step, where a representation of the discrete mechanical response of the IVD needs to be defined in terms of the applied degrees of freedom (DOF) of the MBS. For both methods, an appropriate homogenisation step needs to be applied to obtain the discrete mechanical response of the IVD, i.e. the resulting forces and moments. The goal of this paper was to present an efficient method to approximate the mechanical response of an IVD in an offline computation. In a previous paper (Karajan et al. in Biomech Model Mechanobiol 12(3):453-466, 2012), it was proven that a cubic polynomial for the homogenised forces and moments of the FE model is a suitable choice to approximate the purely elastic response as a coupled function of the DOF of the MBS. In this contribution, the polynomial chaos expansion (PCE) is applied to generate these high-dimensional polynomials. Following this, the main challenge is to determine suitable deformation states of the IVD for pre-computation, such that the polynomials can be constructed with high accuracy and low numerical cost. For the sake of a simple verification, the coupling method and the PCE are applied to the same simplified motion segment of the spine as was used in the previous paper, i.e. two cylindrical vertebrae and a cylindrical IVD in between. In a next step, the loading rates are included as variables in the polynomial response functions to account for a more realistic response of the overall viscoelastic intervertebral disc. Herein, an additive split into elastic and inelastic contributions to the homogenised forces and moments is applied.

Long-term culture of bovine nucleus pulposus explants in a native environment.

PubMed

van Dijk, Bart G M; Potier, Esther; Ito, Keita

2013-04-01

Chronic low back pain is a disease with tremendous financial and social implications, and it is often caused by intervertebral disc degeneration. Regenerative therapies for disc repair are promising treatments, but they need to be tested in physiological models. To develop a physiological in vitro explant model that incorporates the native environment of the intervertebral disc, for example, hypoxia, low glucose, and high tissue osmolarity. Bovine nucleus pulposus (NP) explants were cultured for 42 days in conditions mimicking the native physiological environment. Two different approaches were used to balance the swelling pressure of the NP: raised medium osmolarity or an artificial annulus. Bovine NP explants were either cultured in media with osmolarity balanced at isotonic and hypertonic levels compared with the native tissue or cultured inside a fiber jacket used as an artificial annulus. Oxygen and glucose levels were set at either standard (21% O2 and 4.5 g/L glucose) or physiological (5% O2 and 1 g/L glucose) levels. Samples were analyzed at Day 0, 3, and 42 for tissue composition (water, sulfated glycosaminoglycans, DNA, and hydroxyproline contents and fixed charge density), tissue histology, cell viability, and cellular behavior with messenger RNA (mRNA) expression. Both the hypertonic culture and the artificial annulus approach maintained the tissue matrix composition for 42 days. At Day 3, mRNA expressions of aggrecan, collagen Type I, and collagen Type II in both hypertonic and artificial annulus cultures were not different from Day 0; however, at Day 42, the artificial annulus preserved the mRNA expression closer to Day 0. Gene expressions of matrix metalloprotease 13, tissue inhibitor of matrix metalloprotease 1, and tissue inhibitor of matrix metalloprotease 2 were downregulated under physiological O2 and glucose levels, whereas the other parameters analyzed were not affected. Although the hypertonic culture and the artificial annulus approach are both promising models to test regenerative therapies, the artificial annulus was better able to maintain a cellular behavior closer to the native tissue in longer term cultures. Copyright © 2013 Elsevier Inc. All rights reserved.

Closure of the vertebral canal in human embryos and fetuses.

PubMed

Mekonen, Hayelom K; Hikspoors, Jill P J M; Mommen, Greet; Kruepunga, Nutmethee; Köhler, S Eleonore; Lamers, Wouter H

2017-08-01

The vertebral column is the paradigm of the metameric architecture of the vertebrate body. Because the number of somites is a convenient parameter to stage early human embryos, we explored whether the closure of the vertebral canal could be used similarly for staging embryos between 7 and 10 weeks of development. Human embryos (5-10 weeks of development) were visualized using Amira 3D ® reconstruction and Cinema 4D ® remodelling software. Vertebral bodies were identifiable as loose mesenchymal structures between the dense mesenchymal intervertebral discs up to 6 weeks and then differentiated into cartilaginous structures in the 7th week. In this week, the dense mesenchymal neural processes also differentiated into cartilaginous structures. Transverse processes became identifiable at 6 weeks. The growth rate of all vertebral bodies was exponential and similar between 6 and 10 weeks, whereas the intervertebral discs hardly increased in size between 6 and 8 weeks and then followed vertebral growth between 8 and 10 weeks. The neural processes extended dorsolaterally (6th week), dorsally (7th week) and finally dorsomedially (8th and 9th weeks) to fuse at the midthoracic level at 9 weeks. From there, fusion extended cranially and caudally in the 10th week. Closure of the foramen magnum required the development of the supraoccipital bone as a craniomedial extension of the exoccipitals (neural processes of occipital vertebra 4), whereas a growth burst of sacral vertebra 1 delayed closure until 15 weeks. Both the cranial- and caudal-most vertebral bodies fused to form the basioccipital (occipital vertebrae 1-4) and sacrum (sacral vertebrae 1-5). In the sacrum, fusion of its so-called alar processes preceded that of the bodies by at least 6 weeks. In conclusion, the highly ordered and substantial changes in shape of the vertebral bodies leading to the formation of the vertebral canal make the development of the spine an excellent, continuous staging system for the (human) embryo between 6 and 10 weeks of development. © 2017 Anatomical Society.

Tri-Service Disability Evaluation Systems Database Analysis and Research. Annual Report 2011

DTIC Science & Technology

2011-12-28

aftercare 501 2.6 682: Other cellulitis and abscess 104 2.9 682: Other cellulitis and abscess 463 2.4 300: Anxiety, dissociative and somatoform...procedures 25 3.9 295: Schizophrenic disorders 165 3.6 682: Other cellulitis and abscess 24 3.7 998: Other complications of procedures 164 3.6... cellulitis and abscess 135 3.0 722: Intervertebral disc disorders 17 2.6 996: Complications peculiar to certain specified procedures 134 3.0 738

A retrospective study of nineteen ataxic horses

PubMed Central

Nappert, Germain; Vrins, André; Breton, Luc; Beauregard, Michel

1989-01-01

A retrospective study of 19 ataxic horses admitted to the College of Veterinary Medicine of the University of Montreal during the period of January 1985 to December 1988 is presented. There were 11 cases of cervical vertebral malformation, four of equine degenerative myeloencephalopathy, two of equine protozoal myeloencephalitis, one each of vertebral osteomyelitis and intervertebral disc protrusion. The clinical diagnosis of ataxia in horses requires neurological, radiographic, myelographic, and laboratory examinations. ImagesFigure 1.Figure 2.Figure 3. PMID:17423438

Analysis of Long Bone and Vertebral Failure Patterns.

DTIC Science & Technology

1983-03-01

apophyseal joints, lumbar spondylosis and low back pain in Jayson, M.I.V. (ed) The Lumbar Spine and Back Pain, Pitman Medical, pp. 83-114. PUBLICATIONS...NOTES Material in this report was presented at the International Society for the Study of the Lumbar Spine, Toronto, Canada, June 6-10, 1982. 19. KEY...intervertebral disc and end plate fragments were observed in the vertebral bodies (G84 L2 -3 ) of the upper lumbar levels. Also fragments of trabecular bone

Clinical presentation and outcome of dogs treated medically or surgically for thoracolumbar intervertebral disc protrusion.

PubMed

Crawford, A H; De Decker, S

2017-06-10

To date, few studies have investigated the clinical characteristics of thoracolumbar intervertebral disc protrusion (IVDP). The aim of this retrospective study was to evaluate the presentation and outcome of dogs receiving medical or surgical treatment for thoracolumbar IVDP. Eighty-four dogs were included, with a median age of 9.4 years. German shepherd dogs and Staffordshire bull terriers were the most common breeds. Significantly more surgically treated dogs (n=53) had neurological deficits and were non-ambulatory, compared with medically treated (n=31). Outcome data were available for 27 of 31 medically managed dogs; 11 initially improved, 7 remained stable and 9 deteriorated. Of 18 dogs that initially improved or stabilised, 10 (55.6 per cent) demonstrated recurrence of clinical signs within 12 months of diagnosis. Outcome data were available for 45 of 50 surgically treated dogs that survived to hospital discharge; 34 improved, 9 remained stable and 2 deteriorated following surgery. Of 43 dogs that improved or stabilised with surgical treatment, 11 (25.6 per cent) demonstrated recurrence of clinical signs within 12 months of surgery. Overall, significantly more surgically treated dogs (71.1 per cent) had a successful outcome, consisting of sustained clinical improvement of more than 12 months duration, compared with medically treated dogs (29.6 per cent). British Veterinary Association.

Wear of the Charité® lumbar intervertebral disc replacement investigated using an electro-mechanical spine simulator

PubMed Central

Moghadas, Parshia; Shepherd, Duncan ET; Hukins, David WL

2015-01-01

The Charité® lumbar intervertebral disc replacement was subjected to wear testing in an electro-mechanical spine simulator. Sinusoidally varying compression (0.6–2 kN, frequency 2 Hz), rotation (±2°, frequency 1 Hz), flexion–extension (6° to −3°, frequency 1 Hz) and lateral bending (±2°, frequency 1 Hz) were applied out of phase to specimens immersed in diluted calf serum at 37 °C. The mass of the ultra-high-molecular weight polyethylene component of the device was measured at intervals of 0.5, 1, 2, 3, 4 and 5 million cycles; its volume was also measured by micro-computed tomography. Total mass and volume losses were 60.3 ± 4.6 mg (mean ± standard deviation) and 64.6 ± 6.0 mm3. Corresponding wear rates were 12.0 ± 1.4 mg per million cycles and 12.8 ± 1.2 mm3 per million cycles; the rate of loss of volume corresponds to a mass loss of 11.9 ± 1.1 mg per million cycles, that is, the two sets of measurements of wear agree closely. Wear rates also agree closely with measurements made in another laboratory using the same protocol but using a conventional mechanical spine simulator. PMID:25834002

Rheological and mechanical properties of acellular and cell-laden methacrylated gellan gum hydrogels.

PubMed

Silva-Correia, Joana; Gloria, Antonio; Oliveira, Mariana B; Mano, João F; Oliveira, Joaquim M; Ambrosio, Luigi; Reis, Rui L

2013-12-01

Tissue engineered hydrogels hold great potential as nucleus pulposus substitutes (NP), as they promote intervertebral disc (IVD) regeneration and re-establish its original function. But, the key to their success in future clinical applications greatly depends on its ability to replicate the native 3D micro-environment and circumvent their limitation in terms of mechanical performance. In the present study, we investigated the rheological/mechanical properties of both ionic- (iGG-MA) and photo-crosslinked methacrylated gellan gum (phGG-MA) hydrogels. Steady shear analysis, injectability and confined compression stress-relaxation tests were carried out. The injectability of the reactive solutions employed for the preparation of iGG-MA and phGG-MA hydrogels was first studied, then the zero-strain compressive modulus and permeability of the acellular hydrogels were evaluated. In addition, human intervertebral disc (hIVD) cells encapsulated in both iGG-MA and phGG-MA hydrogels were cultured in vitro, and its mechanical properties also investigated under dynamic mechanical analysis at 37°C and pH 7.4. After 21 days of culturing, hIVD cells were alive (Calcein AM) and the E' of ionic-crosslinked hydrogels and photo-crosslinked was higher than that observed for acellular hydrogels. Our study suggests that methacrylated gellan gum hydrogels present promising mechanical and biological performance as hIVD cells were producing extracellular matrix. Copyright © 2013 Wiley Periodicals, Inc., a Wiley Company.

Intervertebral Disc Cells Produce Interleukins Found in Patients with Back Pain.

PubMed

Zhang, Yejia; Chee, Ana; Shi, Peng; Adams, Sherrill L; Markova, Dessislava Z; Anderson, David Greg; Smith, Harvey E; Deng, Youping; Plastaras, Christopher T; An, Howard S

2016-06-01

To examine the link between cytokines in intervertebral disc (IVD) tissues and axial back pain. In vitro study with human IVD cells cultured from cadaveric donors and annulus fibrosus (AF) tissues from patients. Cultured nucleus pulposus (NP) and AF cells were stimulated with interleukin (IL)-1β. IL-8 and IL-7 gene expression was analyzed using real-time polymerase chain reaction. IL-8 protein was quantified by enzyme-linked immunosorbent assay. After IL-1β stimulation, IL-8 gene expression increased 26,541 fold in NP cells and 22,429 fold in AF cells, whereas protein released by the NP and AF cells increased 2,389- and 1,784-fold, respectively. IL-7 gene expression increased 3.3-fold in NP cells (P < 0.05).Cytokine profiles in AF tissues collected from patients undergoing surgery for back pain (painful group) or scoliosis (controls) were compared by cytokine array. IL-8 protein in the AF tissues from patients with back pain was 1.81-fold of that in controls. IL-7 and IL-10 in AF tissues from the painful group were 6.87 and 4.63 times greater than the corresponding values in controls, respectively (P < 0.05). Inflammatory mediators found in AF tissues from patients with discogenic back pain are likely produced by IVD cells and may play a key role in back pain.

Acidic pH promotes intervertebral disc degeneration: Acid-sensing ion channel -3 as a potential therapeutic target.

PubMed

Gilbert, Hamish T J; Hodson, Nathan; Baird, Pauline; Richardson, Stephen M; Hoyland, Judith A

2016-11-17

The aetiology of intervertebral disc (IVD) degeneration remains poorly understood. Painful IVD degeneration is associated with an acidic intradiscal pH but the response of NP cells to this aberrant microenvironmental factor remains to be fully characterised. The aim here was to address the hypothesis that acidic pH, similar to that found in degenerate IVDs, leads to the altered cell/functional phenotype observed during IVD degeneration, and to investigate the involvement of acid-sensing ion channel (ASIC) -3 in the response. Human NP cells were treated with a range of pH, from that of a non-degenerate (pH 7.4 and 7.1) through to mildly degenerate (pH 6.8) and severely degenerate IVD (pH 6.5 and 6.2). Increasing acidity of pH caused a decrease in cell proliferation and viability, a shift towards matrix catabolism and increased expression of proinflammatory cytokines and pain-related factors. Acidic pH resulted in an increase in ASIC-3 expression. Importantly, inhibition of ASIC-3 prevented the acidic pH induced proinflammatory and pain-related phenotype in NP cells. Acidic pH causes a catabolic and degenerate phenotype in NP cells which is inhibited by blocking ASIC-3 activity, suggesting that this may be a useful therapeutic target for treatment of IVD degeneration.

[The biomechanics of hyperextension injuries of the subaxial cervical spine].

PubMed

Stein, G; Meyer, C; Ingenhoff, L; Bredow, J; Müller, L P; Eysel, P; Schiffer, G

2017-07-01

Hyperextension injuries of the subaxial cervical spine are potentially hazardous due to relevant destabilization. Depending on the clinical condition, neurologic or vascular damage may occur. Therefore an exact knowledge of the factors leading to destabilization is essential. In a biomechanical investigation, 10 fresh human cadaver cervical spine specimens were tested in a spine simulator. The tested segments were C4 to 7. In the first step, physiologic motion was investigated. Afterwards, the three steps of injury were dissection of the anterior longitudinal ligament, removal of the intervertebral disc/posterior longitudinal ligament, and dissection of the interspinous ligaments/ligamentum flavum. After each step, the mobility was determined. Regarding flexion and extension, an increase in motion of 8.36 % after the first step, 90.45 % after the second step, and 121.67 % after the last step was observed. Testing of lateral bending showed an increase of mobility of 7.88 %/27.48 %/33.23 %; axial rotation increased by 2.87 %/31.16 %/45.80 %. Isolated dissection of the anterior longitudinal ligament led to minor destabilization, whereas the intervertebral disc has to be seen as a major stabilizer of the cervical spine. Few finite-element studies showed comparable results. If a transfer to clinical use is undertaken, an isolated rupture of the anterior longitudinal ligament can be treated without surgical stabilization.

MRI features of cervical articular process degenerative joint disease in Great Dane dogs with cervical spondylomyelopathy.

PubMed

Gutierrez-Quintana, Rodrigo; Penderis, Jacques

2012-01-01

Cervical spondylomyelopathy or Wobbler syndrome commonly affects the cervical vertebral column of Great Dane dogs. Degenerative changes affecting the articular process joints are a frequent finding in these patients; however, the correlation between these changes and other features of cervical spondylomyelopathy are uncertain. We described and graded the degenerative changes evident in the cervical articular process joints from 13 Great Danes dogs with cervical spondylomyelopathy using MR imaging, and evaluated the relationship between individual features of cervical articular process joint degeneration and the presence of spinal cord compression, vertebral foraminal stenosis, intramedullary spinal cord changes, and intervertebral disc degenerative changes. Degenerative changes affecting the articular process joints were common, with only 13 of 94 (14%) having no degenerative changes. The most severe changes were evident between C4-C5 and C7-T1 intervertebral spaces. Reduction or loss of the hyperintense synovial fluid signal on T2-weighted MR images was the most frequent feature associated with articular process joint degenerative changes. Degenerative changes of the articular process joints affecting the synovial fluid or articular surface, or causing lateral hypertrophic tissue, were positively correlated with lateral spinal cord compression and vertebral foraminal stenosis. Dorsal hypertrophic tissue was positively correlated with dorsal spinal cord compression. Disc-associated spinal cord compression was recognized less frequently. © 2011 Veterinary Radiology & Ultrasound.

New lumbar disc endoprosthesis applied to the patient's anatomic features.

PubMed

Mróz, Adrian; Skalski, Konstanty; Walczyk, Wojciech

2015-01-01

The paper describes the process of designing, manufacturing and design verification of the intervertebral of a new structure of lumbar disc endoprosthesis - INOP/LSP.1101. Modern and noninvasive medical imagining techniques, make it possible to record results of tests in a digital form, which creates opportunities for further processing. Mimics Innovation Suite software generates three-dimensional virtual models reflecting the real shape and measurements of components of L4-L5 spinal motion segment. With the use of 3D Print technique, physical models of bone structures of the mobile segment of the spine as well as the INOP/LSP.1101 endoprosthesis model were generated. A simplified FEA analysis of stresses in the endoprosthesis was performed to evaluate the designed geometries and materials of the new structure. The endoprosthesis prototype was made of Co28Cr6Mo alloy with the use of selective laser technology. The prototypes were subject to tribological verification with the use of the SBT-03.1 spine simulator. The structure of the endoprosthesis ensures a full reflection of its kinematics, full range of mobility of the motion segment in all anatomical planes as well as restoration of a normal height of the intervertebral space and curvature of the lordosis. The results of the tribological tests confirmed that SLM technology has the potential for production of the human bone and jointendoprostheses.

Higher risk for cervical herniated intervertebral disc in physicians: A retrospective nationwide population-based cohort study with claims analysis.

PubMed

Liu, Cheng; Huang, Chien-Cheng; Hsu, Chien-Chin; Lin, Hung-Jung; Guo, How-Ran; Su, Shih-Bin; Wang, Jhi-Joung; Weng, Shih-Feng

2016-10-01

There is no study about cervical herniated intervertebral disc (cervical HIVD) in physicians in the literature; therefore, we conceived a retrospective nationwide, population-based cohort study to elucidate the topic. We identified 26,038 physicians, 33,057 non-physician healthcare providers (HCPs), and identical numbers of non-HCP references (i.e., general population). All cohorts matched a 1:1 ratio with age and gender, and each were chosen from the Taiwan National Health Insurance Research Database (NHIRD). We compared cervical HIVD risk among physicians, nonphysician HCPs, and non-HCP references and performed a follow-up between 2007 and 2011. We also made comparisons among physician specialists. Both physicians and nonphysician HCPs had higher cervical HIVD risk than non-HCP references (odds ratio [OR]: 1.356; 95% confidence interval (CI): 1.162-1.582; OR: 1.383; 95% CI: 1.191-1.605, respectively). There was no significant difference of cervical HIVD risk between physicians and nonphysician HCPs. In the comparison among physician specialists, orthopedists had a higher cervical HIVD risk than other specialists, but the difference was not statistically significant (adjusted OR: 1.547; 95% CI: 0.782-3.061). Physicians are at higher cervical HIVD risk than the general population. Because unknown confounders could exist, further prospective studies are needed to identify possible causation.

Comparison between cervical disc arthroplasty and conservative treatment for patients with single level cervical radiculopathy at C5/6.

PubMed

He, Axiang; Xie, Dong; Qu, Bo; Cai, Xiaomin; Kong, Qin; Yang, Lili; Chen, Xiongsheng; Jia, Lianshun

2018-01-31

Cervical radiculopathy is a common disease that affects millions of people. Patients usually are managed by conservative therapy and surgical treatments. To compare the clinical outcomes between cervical disc arthroplasty (CDA) and conservative management for patients with single level cervical radiculopathy at C5/6. Seventy-two patients with cervical radiculopathy that only affect C5/6 joints were included and thirty-two of them received CDA surgery, and forty patients were treated with conservative management. All the patients were followed up around 4 years. Cervical curvature, cervical range of motion (CROM), horizontal displacement of cervical spine, and intervertebral gap were measured by radiological examination. All the patients have comparable disease severity based on pre-surgical radiological assessments. At the 4-year follow-up examination, patients with CDA surgery had less CROM at C5/6 level, while greater CROM at C4/5 level, than control group. Similarly, the horizontal displacement in CDA group decreased at C5/6 vertebrae, and increased at C4/5 level at the 4-year follow-up examination. The intervertebral gaps of patients in CDA group were larger than control group at one-year and last follow-up examination. CDA surgery stabilized C5/6 vertebrae and increased the CROM and horizontal displacement of upper adjacent C4/5 vertebrae. Copyright © 2018. Published by Elsevier Ltd.

A 20-Year Prospective Longitudinal Study of Degeneration of the Cervical Spine in a Volunteer Cohort Assessed Using MRI: Follow-up of a Cross-Sectional Study.

PubMed

Daimon, Kenshi; Fujiwara, Hirokazu; Nishiwaki, Yuji; Okada, Eijiro; Nojiri, Kenya; Watanabe, Masahiko; Katoh, Hiroyuki; Shimizu, Kentaro; Ishihama, Hiroko; Fujita, Nobuyuki; Tsuji, Takashi; Nakamura, Masaya; Matsumoto, Morio; Watanabe, Kota

2018-05-16

Few studies have addressed in detail long-term degenerative changes in the cervical spine. In this study, we evaluated the progression of degenerative changes of the cervical spine that occurred over a 20-year period in an originally healthy cohort. We also sought to clarify the relationship between the progression of cervical degenerative changes and the development of clinical symptoms. For this prospective follow-up investigation, we recruited 193 subjects from an original cohort of 497 participants who had undergone magnetic resonance imaging (MRI) of the cervical spine between 1993 and 1996. The subjects were asked about the presence or absence of cervical spine-related symptoms. Degenerative changes of the cervical spine were assessed on MRI using an original numerical grading system. The relationship between the progression of degenerative changes and the onset of clinical symptoms was evaluated by logistic regression analysis. Degeneration in the cervical spine was found to have progressed in 95% of the subjects during the 20-year period. The finding of a decrease in signal intensity of the intervertebral disc progressed in a relatively high proportion of the subjects in all age groups and occurred with similar frequency (around 60%) at all intervertebral disc levels. The rate of progression of other structural failures on MRI increased with age and was highest at C5-C6. The progression of foraminal stenosis was associated with the onset of upper-limb pain (odds ratio, 4.71 [95% confidence interval, 1.02 to 21.7]). A progression of degenerative changes in the cervical spine on MRI over the 20-year period was detected in nearly all subjects. There was no relationship between the progression of degeneration on MRI and the development of clinical symptoms, with the exception of an association found between foraminal stenosis and upper-limb pain. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Synovial joint formation requires local Ext1 expression and heparan sulfate production in developing mouse embryo limbs and spine.

PubMed

Mundy, Christina; Yasuda, Tadashi; Kinumatsu, Takashi; Yamaguchi, Yu; Iwamoto, Masahiro; Enomoto-Iwamoto, Motomi; Koyama, Eiki; Pacifici, Maurizio

2011-03-01

Heparan sulfate proteoglycans (HSPGs) regulate a number of major developmental processes, but their roles in synovial joint formation remain unknown. Here we created conditional mouse embryo mutants lacking Ext1 in developing joints by mating Ext1(f/f) and Gdf5-Cre mice. Ext1 encodes a subunit of the Ext1/Ext2 Golgi-associated protein complex responsible for heparan sulfate (HS) synthesis. The proximal limb joints did form in the Gdf5-Cre;Ext1(f/f) mutants, but contained an uneven articulating superficial zone that expressed very low lubricin levels. The underlying cartilaginous epiphysis was deranged as well and displayed random patterns of cell proliferation and matrillin-1 and collagen IIA expression, indicative of an aberrant phenotypic definition of the epiphysis itself. Digit joints were even more affected, lacked a distinct mesenchymal interzone and were often fused likely as a result of local abnormal BMP and hedgehog activity and signaling. Interestingly, overall growth and lengthening of long bones were also delayed in the mutants. To test whether Ext1 function is needed for joint formation at other sites, we examined the spine. Indeed, entire intervertebral discs, normally composed by nucleus pulposus surrounded by the annulus fibrosus, were often missing in Gdf5-Cre;Ext1(f/f) mice. When disc remnants were present, they displayed aberrant organization and defective joint marker expression. Similar intervertebral joint defects and fusions occurred in Col2-Cre;β-catenin(f/f) mutants. The study provides novel evidence that local Ext1 expression and HS production are needed to maintain the phenotype and function of joint-forming cells and coordinate local signaling by BMP, hedgehog and Wnt/β-catenin pathways. The data indicate also that defects in joint formation reverberate on, and delay, overall long bone growth. Copyright © 2011 Elsevier Inc. All rights reserved.

Biomechanics of a Fixed–Center of Rotation Cervical Intervertebral Disc Prosthesis

PubMed Central

Crawford, Neil R.; Baek, Seungwon; Sawa, Anna G.U.; Safavi-Abbasi, Sam; Sonntag, Volker K.H.; Duggal, Neil

2012-01-01

Background Past in vitro experiments studying artificial discs have focused on range of motion. It is also important to understand how artificial discs affect other biomechanical parameters, especially alterations to kinematics. The purpose of this in vitro investigation was to quantify how disc replacement with a ball-and-socket disc arthroplasty device (ProDisc-C; Synthes, West Chester, Pennsylvania) alters biomechanics of the spine relative to the normal condition (positive control) and simulated fusion (negative control). Methods Specimens were tested in multiple planes by use of pure moments under load control and again in displacement control during flexion-extension with a constant 70-N compressive follower load. Optical markers measured 3-dimensional vertebral motion, and a strain gauge array measured C4-5 facet loads. Results Range of motion and lax zone after disc replacement were not significantly different from normal values except during lateral bending, whereas plating significantly reduced motion in all loading modes (P < .002). Plating but not disc replacement shifted the location of the axis of rotation anteriorly relative to the intact condition (P < 0.01). Coupled axial rotation per degree of lateral bending was 25% ± 48% greater than normal after artificial disc replacement (P = .05) but 37% ± 38% less than normal after plating (P = .002). Coupled lateral bending per degree of axial rotation was 37% ± 21% less than normal after disc replacement (P < .001) and 41% ± 36% less than normal after plating (P = .001). Facet loads did not change significantly relative to normal after anterior plating or arthroplasty, except that facet loads were decreased during flexion in both conditions (P < .03). Conclusions In all parameters studied, deviations from normal biomechanics were less substantial after artificial disc placement than after anterior plating. PMID:25694869

A Clinical Comparison of Anterior Cervical Plates Versus Stand-Alone Intervertebral Fusion Devices for Single-Level Anterior Cervical Discectomy and Fusion Procedures.

PubMed

Panchal, Ripul R; Kim, Kee D; Eastlack, Robert; Lopez, John; Clavenna, Andrew; Brooks, Daina M; Joshua, Gita

2017-03-01

To compare radiologic and clinical outcomes, including rates of dysphagia and dysphonia, using a no-profile stand-alone intervertebral spacer with integrated screw fixation versus an anterior cervical plate and spacer construct for single-level anterior cervical discectomy and fusion (ACDF) procedures. This multicenter, randomized, prospective study included 54 patients with degenerative disc disease requiring ACDF at a single level at C3-C7. Twenty-six patients underwent single-level ACDF with stand-alone spacers, and 28 with plate fixation and spacers. Analyses were based on comparison of perioperative outcomes, radiologic and clinical metrics, and incidence of dysphagia and/or dysphonia. Mean patient age was 48.8 ± 10.1years (53.7% female). No significant differences were observed between groups in operative time (101.8 ± 34.4 minutes, 114.4 ± 31.5 minutes), estimated blood loss (44.8 ± 76.5 mL, 82.5 ± 195.1 mL), or length of hospital stay (1.2 ± 0.6 days, 1.3 ± 0.6 days). Mean visual analog scale pain scores and Neck Disability Index scores improved significantly from preoperative to last follow-up (10.8 ± 2.6 months) in both groups (P < 0.05). Mean Voice Handicap Index and Eating Assessment Tool scores improved significantly from discharge to last follow-up in both groups (P < 0.05). From discharge to 6 months, the stand-alone spacers group consistently demonstrated greater improvement in Voice Handicap Index. Preoperative intervertebral disc and neuroforaminal heights increased significantly across treatment groups (P < 0.01), and no cases required surgical revision at index or adjacent levels. Anterior cervical discectomy and fusion with stand-alone spacers resulted in similar clinical and radiologic outcomes as compared with plate and spacers and may help minimize postoperative dysphonia. Copyright © 2016 Elsevier Inc. All rights reserved.

Vertebral Augmentation can Induce Early Signs of Degeneration in the Adjacent Intervertebral Disc: Evidence from a Rabbit Model.

PubMed

Feng, Zhiyun; Chen, Lunhao; Hu, Xiaojian; Yang, Ge; Wang, Yue; Chen, Zhong

2018-04-11

An experimental study. The aim of this study was to determine the effect of polymethylmethacrylate (PMMA) augmentation on the adjacent disc. Vertebral augmentation with PMMA reportedly may predispose the adjacent vertebra to fracture. The influence of PMMA augmentation on the adjacent disc, however, remains unclear. Using a retroperitoneal approach, PMMA augmentation was performed for 23 rabbits. For each animal, at least one vertebra was augmented with 0.2 to 0.3 mL PMMA. The disc adjacent to the augmented vertebra and a proximal control disc were studied using magnetic resonance (MR) imaging, histological and molecular level evaluation at 1, 3, and 6 months postoperatively. Marrow contact channels in the endplate were quantified in histological slices and number of invalid channels (those without erythrocytes inside) was rated. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) was performed to determine disc cell apoptosis. On MR images, the signal and height of the adjacent disc did not change 6 months after vertebral augmentation. Histological scores of the adjacent disc increased over time, particularly for the nucleus pulposus. The adjacent disc had greater nucleus degeneration score than the control disc at 3 months (5.7 vs. 4.5, P < 0.01) and 6 months (6.9 vs. 4.4, P < 0.001). There were more invalid marrow contact channels in the endplate of augmented vertebra than the control (43.3% vs. 11.1%, P < 0.01). mRNA of ADAMTS-5, MMP-13, HIF-1α, and caspase-3 were significantly upregulated in the adjacent disc at 3 and 6 months (P < 0.05 for all). In addition, there were more TUNEL-positive cells in the adjacent disc than in the control disc (43.4% vs. 24.0%, P < 0.05) at 6 months postoperatively. Vertebral augmentation can induce early degenerative signs in the adjacent disc, which may be due to impaired nutrient supply to the disc. N/A.

The role of rigid vs. dynamic instrumentation for stabilization of the degenerative lumbosacral spine.

PubMed

Korovessis, Panagiotis; Papazisis, Zisis; Lambiris, Elias

2002-01-01

This is a prospective comparative randomised study to compare the immediately postoperative effects of a rigid versus dynamic instrumentation for degenerative spine disease and stenosis on the standing sagittal lumbar spine alignment and to investigate if a dynamic spine system can replace the commonly used rigid systems in order to avoid the above mentioned disadvantages of rigid fixation. 15 randomly selected patients received the rigid instrumentation SCS and an equal number of randomly selected patients the dynamic TWINFLEX device for spinal stenosis associated degenerative lumbar disease. The age of the patients, who received rigid and dynamic instrumentation was 65 +/- 9 years and 62 +/- 10 years respectively. All patients had standing spine radiographs preoperatively and three months postoperatively. The parameters that were measured and compared pre- to postoperatively were: lumbar lordosis (L1-S1), total lumbar lordosis (T12-S1), sacral tilt, distal lordosis (L4-S1), intervertebral angulation, vertebral inclination and disc index. The instrumented levels in the spines that received rigid and dynamic instrumentation were 3.5 +/- 0.53 and 3 +/- 0.7 respectively. The instrumented levels from L3 to L5 were 23, the lumbosacral junction was instrumented in 3 patients of group A and in 4 patients of group B. Lumbar lordosis did not significantly change postoperatively, while total lordosis was significantly (P=0.04) increased in the patients who received the rigid instrumentation, while it was significantly (P=0.012) decreased in the group B. Intervertebral angulation of the non-instrumented level L1-L2 was increased in the group A (P=0.01), while the dynamic instrumentation increased (P=0.02) the intervertebral inclination of the adjacent level L2-L3, immediately above the uppermost instrumented level. Distal lordosis and sacral tilt did not change in any patient in both groups. Both instrumentations did not change the lateral vertebral inclination of L1 to L5 vertebrae. Rigid instrumentation increased the lordotic inclination of L5 (P=0.03) and of S1 (P=0.03). Rigid instrumentation increased (P=0.04) the intervertebral angulation at the uppermost instrumented level L3-L4 The most significant change in vertebral angulation was achieved at the instrumented level L4-L5 by the dynamic (P=0.007) and rigid (0.05). The disc index at the level L2-L3 was increased by both instrumentation [dynamic P=0.007 and rigid (P=0.02)]. The index L3-L4 was increased following dynamic fixation (P=0.0007). The disc index L4-L5 was postoperatively increased by both types of instrumentation (rigid P=0.006, dynamic P=0.02). The disc index L5-S1 did not significantly change postoperatively by either system. Both rigid and dynamic instrumentations restored lumbar lordosis, sacral tilt, distal lordosis and increased the foraminal diameter at the level L4-L5 resulting in an indirect decompression of the nerve roots at this level . Both rigid and dynamic instrumentations applied in the lumbosacral spine to treat degenerative disease secured L3 to S1 sagittal spine profile close to preoperative levels, that should theoretically guarantee a pain-free postoperative course. This study supports the belief that the dynamic system can be used with the same indications with the rigid in degenerative lumbar spine because it can offer equally good short-term results regarding sagittal spine alignment while simultaneously it has the previously mentioned advantages (avoidance stress shielding etc).

In vitro measurement of nucleus pulposus swelling pressure: A new technique for studies of spinal adaptation to gravity

NASA Technical Reports Server (NTRS)

Hargens, A. R.; Glover, M. G.; Mahmood, M. M.; Gott, S.; Garfin, S. R.; Ballard, R.; Murthy, G.; Brown, M. D.

1992-01-01

Swelling of the intervertebral disc nucleus pulposus is altered by posture and gravity. We have designed and tested a new osmometer for in vitro determination of nucleus pulposus swelling pressure. The functional principle of the osmometer involves compressing a sample of nucleus pulposus with nitrogen gas until saline pressure gradients across a 0.45 microns Millipore filter are eliminated. Swelling pressure of both pooled dog and pooled pig lumbar disc nucleus pulposus were measured on the new osmometer and compared to swelling pressures determined using the equilibrium dialysis technique. The osmometer measured swelling pressures comparable to those obtained by the dialysis technique. This osmometer provides a rapid, direct, and accurate measurement of swelling pressure of the nucleus pulposus.

Quantitative measurement of intervertebral disc signal using MRI.

PubMed

Niemeläinen, R; Videman, T; Dhillon, S S; Battié, M C

2008-03-01

To investigate the spinal cord as an alternative intra-body reference to cerebrospinal fluid (CSF) in evaluating thoracic disc signal intensity. T2-weighted magnetic resonance imaging (MRI) images of T6-T12 were obtained using 1.5 T machines for a population-based sample of 523 men aged 35-70 years. Quantitative data on the signal intensities were acquired using an image analysis program (SpEx). A random sample of 30 subjects and intraclass correlation coefficients (ICC) were used to examine the repeatability of the spinal cord measurements. The validity of using the spinal cord as a reference was examined by correlating cord and CSF samples. Finally, thoracic disc signal was validated by correlating it with age without adjustment and adjusting for either cord or CSF. Pearson's r was used for correlational analyses. The repeatability of the spinal cord signal measurements was extremely high (>or=0.99). The correlations between the signals of spinal cord and CSF by level were all above 0.9. The spinal cord-adjusted disc signal and age correlated similarly with CSF-adjusted disc signal and age (r=-0.30 to -0.40 versus r=-0.26 to -0.36). Adjacent spinal cord is a good alternative reference to the current reference standard, CSF, for quantitative measurements of disc signal intensity. Clearly fewer levels were excluded when using spinal cord as compared to CSF due to missing reference samples.

A Systematic Review of the Safety and Efficacy of Mesenchymal Stem Cells for Disc Degeneration: Insights and Future Directions for Regenerative Therapeutics

PubMed Central

Yim, Rita Lok-Hay; Lee, Juliana Tsz-Yan; Bow, Cora H.; Meij, Björn; Leung, Victor; Cheung, Kenneth M.C.; Vavken, Patrick

2014-01-01

Intervertebral disc degeneration is associated with low-back pain. Mesenchymal stem cells (MSCs) have been used to “regenerate” the disc. The aim of this study was to perform a systematic review of comparative controlled studies that have assessed the safety and efficacy of using MSCs for disc regeneration. Literature databases were extensively searched. Trial design, subject-type, MSC sources, injection method, disc assessment, outcome intervals, and complication events were assessed. Validity of each study was performed. Twenty-four animal studies were included with 20.8% of the studies reporting randomization of groups. Trials in humans fulfilling inclusion criteria were not noted. The studies represented 862 discs that were injected with MSCs and 1,603 discs as controls. All three types of MSCs (ie, bone marrow, synovial, and adipose tissues) showed successful inhibition of disc degeneration. Bone-marrow-derived MSCs demonstrated superior quality of repair compared with other non-MSC treatments. A 2.7% overall complication rate was noted, whereby complications were noted only in rabbits. Overall, evidence suggested that MSCs increased disc space height in the majority of animal models. This is the first systematic review to assess the safety and efficacy of MSCs for the treatment of disc degeneration. Short-term MSC transplantation is safe and effective; however, additional, larger, and higher-quality studies are needed to assess the long-term safety and efficacy. Inconsistencies in methodological design and outcome parameters prevent any robust conclusions. Human-based clinical trials are needed. Recommendations are further made to improve efficacy, reduce potential complications, and standardize techniques for future studies. PMID:25050446

Surgical management of giant lumbar disc herniation: analysis of 154 patients over a decade.

PubMed

Akhaddar, A; Belfquih, H; Salami, M; Boucetta, M

2014-10-01

We describe a decade of our experience in the surgical management of patients with giant lumbar intervertebral disc herniation (GILID). This is a case series of patients operated for a GILID between 2000 and 2009. Among 1334 patients eligible for the present study: 154 patients presented with GILID (study group) and 1180 patients without GILID (control group). Clinical symptoms and preoperative imaging results were obtained from medical records. Complications and long-term results were assessed. This retrospective study documents the characteristic features between patients with and without GILID. The difference in the incidence of female patients was statistically significant between the study group and the control group as was the mean duration of symptoms, hyperalgic radicular pain, bilaterality of symptoms, preoperative motor deficit, central location of lumbar disc herniation (LDH), contained herniation and recurrence of LDH. GILIDs are a distinct entity: they are distinctly uncommon compared with smaller herniations, patients were statistically more likely to be hyperalgic with bilateral radicular pain and often associated with neurological deficits. The majority of patients do not display a cauda equina syndrome (CES). Low lumbar disc sites are mostly affected and disc fragments are more likely to be central-uncontained. The recurrence rate is lower for GILIDs. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Interleukin 1-beta upregulates brain-derived neurotrophic factor, neurotrophin 3 and neuropilin 2 gene expression and NGF production in annulus cells.

PubMed

Gruber, H E; Hoelscher, G L; Bethea, S; Hanley, E N

2012-11-01

The relationship between disc cells, nerves and pain production in the intervertebral disc is poorly understood. Neurotrophins, signaling molecules involved in the survival, differentiation and migration of neurons, and neurite outgrowth, are expressed in non-neuronal tissues including the disc. We hypothesized that three-dimensional exposure of human disc cells to the proinflammatory cytokine IL-1ß in vitro would elevate neurotrophin gene expression levels and production of nerve growth factor (NGF). Cells isolated from Thompson grade III and IV discs were cultured for 14 days under control conditions or with addition of 10(2) pM IL-1ß; mRNA was isolated and conditioned media assayed for NGF content. IL-1ß exposure in three-dimensional culture significantly increased expression of neurotrophin 3, brain-derived neurotrophic factor, and neuropilin 2 compared to controls. IL-1ß-exposed cells showed significantly increased NGF production compared to controls. Findings support our hypothesis, expand previous data concerning expression of neurotrophins, and provide the first documented expression of neurotrophin 3 and neuropilin 2. Our results have direct translational relevance, because they address the primary clinical issue of low back pain and open the possibility of novel analgesic therapies using specific small-molecular antagonists to neurotrophins.

Spaceflight-Induced Bone Loss Alters Failure Mode and Reduces Bending Strength in Murine Spinal Segments

PubMed Central

Berg-Johansen, Britta; Liebenberg, Ellen C.; Li, Alfred; Macias, Brandon R.; Hargens, Alan R.; Lotz, Jeffrey C.

2017-01-01

Intervertebral disc herniation rates are quadrupled in astronauts following spaceflight. While bending motions are main contributors to herniation, the effects of microgravity on the bending properties of spinal discs are unknown. Consequently, the goal of this study was to quantify the bending properties of tail discs from mice with or without microgravity exposure. Caudal motion segments from six mice returned from a 30-day Bion M1 mission and eight vivarium controls were loaded to failure in four-point bending. After testing, specimens were processed using histology to determine the location of failure, and adjacent motion segments were scanned with micro-computed tomography (μCT) to quantify bone properties. We observed that spaceflight significantly shortened the nonlinear toe region of the force-displacement curve by 32% and reduced the bending strength by 17%. Flight mouse spinal segments tended to fail within the growth plate and epiphyseal bone, while controls tended to fail at the disc-vertebra junction. Spaceflight significantly reduced vertebral bone volume fraction, bone mineral density, and trabecular thickness, which may explain the tendency of flight specimens to fail within the epiphyseal bone. Together, these results indicate that vertebral bone loss during spaceflight may degrade spine bending properties and contribute to increased disc herniation risk in astronauts. PMID:26285046

Fatal herpes simplex infection in a pygmy African hedgehog (Atelerix albiventris).

PubMed

Allison, N; Chang, T C; Steele, K E; Hilliard, J K

2002-01-01

An adult pygmy African hedgehog developed acute posterior paresis attributed to a prolapsed intervertebral disc diagnosed by C-T scan. Corticosteroid therapy resulted in prompt resolution of the ataxia, but 2 weeks later the animal became anorexic and died. Macroscopically, the liver was stippled with punctate off-white foci which were confirmed microscopically to be foci of necrosis. Numerous hepatocytes contained intranuclear inclusions and syncytial cell formation was also present. A herpes virus was isolated and identified by fluorescent antibody and polymerase chain reaction studies as herpesvirus simplex type 1. To our knowledge, this is the first report of herpes infection in the African hedgehog and the first time herpes simplex has been identified as a cause of disease in insectivores.

Spinal infections: clinical and imaging features.

PubMed

Arbelaez, Andres; Restrepo, Feliza; Castillo, Mauricio

2014-10-01

Spinal infections represent a group of rare conditions affecting vertebral bodies, intervertebral discs, paraspinal soft tissues, epidural space, meninges, and spinal cord. The causal factors, clinical presentations, and imaging features are a challenge because the difficulty to differentiate them from other conditions, such as degenerative and inflammatory disorders and spinal neoplasm. They require early recognition because delay diagnosis, imaging, and intervention may have devastating consequences especially in children and the elderly. This article reviews the most common spinal infections, their pathophysiologic, clinical manifestation, and their imaging findings.

Intradiscal pressure variation under spontaneous ventilation

NASA Astrophysics Data System (ADS)

Roriz, Paulo; Ferreira, J.; Potes, J. C.; Oliveira, M. T.; Santos, J. L.; Simões, J. A.; Frazão, O.

2014-05-01

The pressure measured in the intervertebral discs is a response to the loads acting on the spine. External loads, such as the reaction forces resulting from locomotion, manual handling and collisions are probably the most relevant in studying spine trauma. However, the physiological functions such as breathing and hearth rate also participate in subtle variations of intradiscal pressure that can be observed only in vivo at resting. Present work is an effort to measure the effect of breathing on intradiscal pressure of an anesthetized sheep.

Risk Factors for Discharge from the Army with a Permanent Disability

DTIC Science & Technology

2008-07-01

U.S. population) and concurrent increased BMI and higher body fat among Army recruits, or it could reflect changes in occupational exposures in the...722.1 Displacement of Thoracic or Lumbar Intervertebral Disc w/o Myelopathy 613 2.45% 733.1 Pathological Fracture 530 2.11% * Percents are given...Percent of total* 414.0 Coronary Atherosclerosis 228 17.97% 733.1 Pathological Fracture 121 9.54% 443.0 Raynaud’s Syndrome 75 5.91% 729.5 Pain in

Backache due to alkaptonuria in a middle aged man.

PubMed

Arshad, Abdul Rehman; Awan, Muhammad Younus

2013-12-01

Alkaptonuria is a rare cause of backache. A 55 years old gentleman, a retired army personal had been having pain and stiffness in the spine for the last 15 years, accompanied by bluish black discolouration of face and hands. Kyphosis and reduced movement of spine were present. Other joints were spared. Osler spots were visible on the sclera. X-rays revealed calcification of intervertebral discs. Asymptomatic renal stone was identified. There was no cardiac involvement. Symptomatic care was provided.

Medical Surveillance Monthly Report. Volume 21, Number 5

DTIC Science & Technology

2014-05-01

11.5 1,495 81.1 722 Intervertebral disc disorders 1,832 11.4 976 53.3 401 Essential hypertension 1,808 11.2 704 38.9 723 Other disorders of cervical...Accessed 14 May 2014. 5. Department of the Navy. Marine Corps Order 1500.54A. Subject: Marine Corps Martial Arts Program. http://www.marines.mil/ Portals ...Arts Program. 2011. Washington, DC: Headquarters, U.S. Marine Corps. http://www. marines.mil/ Portals /59/Publications/MCRP%20 3-02B%20PT%201.pdf

Regeneration of spine disc and joint cartilages under temporal and space modulated laser radiation

NASA Astrophysics Data System (ADS)

Sobol, E.; Shekhter, A.; Baskov, A.; Baskov, V.; Baum, O.; Borchshenko, I.; Golubev, V.; Guller, A.; Kolyshev, I.; Omeltchenko, A.; Sviridov, A.; Zakharkina, O.

2009-02-01

The effect of laser radiation on the generation of hyaline cartilage in spine disc and joints has been demonstrated. The paper considers physical processes and mechanisms of laser regeneration, presents results of investigations aimed to optimize laser settings and to develop feedback control system for laser reconstruction of spine discs. Possible mechanisms of laser-induced regeneration include: (1) Space and temporary modulated laser beam induces nonhomogeneous and pulse repetitive thermal expansion and stress in the irradiated zone of cartilage. Mechanical effect due to controllable thermal expansion of the tissue and micro and nano gas bubbles formation in the course of the moderate (up to 45-50 oC) heating of the NP activate biological cells (chondrocytes) and promote cartilage regeneration. (2) Nondestructive laser radiation leads to the formation of nano and micro-pores in cartilage matrix. That promotes water permeability and increases the feeding of biological cells. Results provide the scientific and engineering basis for the novel low-invasive laser procedures to be used in orthopedics for the treatment cartilages of spine and joints. The technology and equipment for laser reconstruction of spine discs have been tested first on animals, and then in a clinical trial. Since 2001 the laser reconstruction of intervertebral discs have been performed for 340 patients with chronic symptoms of low back or neck pain who failed to improve with non-operative care. Substantial relief of back pain was obtained in 90% of patients treated who returned to their daily activities. The experiments on reparation of the defects in articular cartilage of the porcine joints under temporal and spase modulated laser radiation have shown promising results.

Altered Helical Axis Patterns of the Lumbar Spine Indicate Increased Instability with Disc Degeneration

PubMed Central

Ellingson, Arin M.; Nuckley, David J.

2014-01-01

Although the causes of low back pain are poorly defined and indistinct, degeneration of the intervertebral disc is most often implicated as the origin of pain. The biochemical and mechanical changes associated with degeneration result in the discs’ inability to maintain structure and function, leading to spinal instability and ultimately pain. Traditionally, a clinical exam assessing functional range-of-motion coupled with T2-weighted MRI revealing disc morphology are used to evaluate spinal health; however, these subjective measures fail to correlate well with pain or provide useful patient stratification. Therefore, improved quantification of spinal motion and objective MRI measures of disc health are necessary. An instantaneous helical axis (IHA) approach provides rich temporal three-dimensional data describing the pathway of motion, which is easily visualized. Eighteen cadaveric osteoligamentous lumbar spines (L4-5) from throughout the degenerative spectrum were tested in a pure moment fashion. IHA were calculated for flexion-extension and lateral bending. A correlational study design was used to determine the relationship between disc measurements from quantitative T2* MRI and IHA metrics. Increased instability and out-of-plane rotation with diminished disc health was observed during lateral bending, but not flexion-extension. This new analysis strategy examines the entire pathway of motion, rather than simplifying spinal kinematics to its terminal ends of motion and provides a more sensitive kinematic measurement of disc health. Ultimately, through the use of 3D dynamic fluoroscopy or similar methods, a patient's functional IHA in lateral bending may be measured and used to assess their disc health for diagnosis, progression tracking, and treatment evaluation. PMID:25481221

Noninvasive Assessment of Biochemical and Mechanical Properties of Lumbar Discs Through Quantitative Magnetic Resonance Imaging in Asymptomatic Volunteers.

PubMed

Foltz, Mary H; Kage, Craig C; Johnson, Casey P; Ellingson, Arin M

2017-11-01

Intervertebral disc degeneration is a prevalent phenomenon associated with back pain. It is of critical clinical interest to discriminate disc health and identify early stages of degeneration. Traditional clinical T2-weighted magnetic resonance imaging (MRI), assessed using the Pfirrmann classification system, is subjective and fails to adequately capture initial degenerative changes. Emerging quantitative MRI techniques offer a solution. Specifically, T2* mapping images water mobility in the macromolecular network, and our preliminary ex vivo work shows high predictability of the disc's glycosaminoglycan content (s-GAG) and residual mechanics. The present study expands upon this work to predict the biochemical and biomechanical properties in vivo and assess their relationship with both age and Pfirrmann grade. Eleven asymptomatic subjects (range: 18-62 yrs) were enrolled and imaged using a 3T MRI scanner. T2-weighted images (Pfirrmann grade) and quantitative T2* maps (predict s-GAG and residual stress) were acquired. Surface maps based on the distribution of these properties were generated and integrated to quantify the surface volume. Correlational analyses were conducted to establish the relationship between each metric of disc health derived from the quantitative T2* maps with both age and Pfirrmann grade, where an inverse trend was observed. Furthermore, the nucleus pulposus (NP) signal in conjunction with volumetric surface maps provided the ability to discern differences during initial stages of disc degeneration. This study highlights the ability of T2* mapping to noninvasively assess the s-GAG content, residual stress, and distributions throughout the entire disc, which may provide a powerful diagnostic tool for disc health assessment.

Which iodinated contrast media is the least cytotoxic to human disc cells?

PubMed

Kim, Kyung-Hyun; Park, Jeong-Yoon; Park, Hyo-Suk; Kuh, Sung-Uk; Chin, Dong-Kyu; Kim, Keun-Su; Cho, Yong-Eun

2015-05-01

Iodinated contrast media (CM) is commonly used for various intradiscal injections such as in discography and endoscopic spinal surgery. However, CM has been shown to be toxic to renal tissue due to its ionic strength and osmolarity and as a result of iodine-induced cytotoxicity, which has raised concern over whether there are similar negative effects on disc cells. This in vitro study was designed to identify the least cytotoxic iodinated CM to the human disc cell among four different physiochemical iodinated contrast dyes. In vitro laboratory study. Intervertebral disc tissue was obtained by discectomy from a total of 10 lumbar disc patients undergoing surgery and disc cells were isolated. The human disc cells were grown in 3D alginate bead culture with 0, 0.1, 10, and 100 mg/mL CM solutions (ionic dimer, ionic monomer, non-ionic dimer, and non-ionic monomer) and mannitol as a control for 2 days. The living cells were analyzed with trypan blue staining. Fluorescence-activated cell sorting analysis was performed using Annexin V and propidium iodide (PI) and 3D alginate bead immunostaining to identify live, apoptotic, and necrotic cells. Human disc cell death was time- and dose-dependent in response to CM and more necrosis was observed than apoptosis. In addition, non-ionic dimeric CM (iodixanol) showed the least toxic effect on human disc cells, followed by non-ionic monomeric (iopromide), ionic dimeric (ioxaglate), and ionic monomeric CM (ioxithalamate). Contrast media is cytotoxic to human disc cells in a dose- and time-dependent manner. This in vitro study revealed that, among four different CM preparations, non-ionic dimeric CM is the least detrimental to human disc cell viability. Careful attention should be paid to the type of CM chosen for discography and endoscopic spinal surgery. It is also necessary to investigate the detrimental effects of CM on disc cells and disc degeneration in further in vivo studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Quantitative T2 Magnetic Resonance Imaging Compared to Morphological Grading of the Early Cervical Intervertebral Disc Degeneration: An Evaluation Approach in Asymptomatic Young Adults

PubMed Central

Han, Zhihua; Shao, Lixin; Xie, Yan; Wu, Jianhong; Zhang, Yan; Xin, Hongkui; Ren, Aijun; Guo, Yong; Wang, Deli; He, Qing; Ruan, Dike

2014-01-01

Objective The objective of this study was to evaluate the efficacy of quantitative T2 magnetic resonance imaging (MRI) for quantifying early cervical intervertebral disc (IVD) degeneration in asymptomatic young adults by correlating the T2 value with Pfirrmann grade, sex, and anatomic level. Methods Seventy asymptomatic young subjects (34 men and 36 women; mean age, 22.80±2.11 yr; range, 18–25 years) underwent 3.0-T MRI to obtain morphological data (one T1-fast spin echo (FSE) and three-plane T2-FSE, used to assign a Pfirrmann grade (I–V)) and for T2 mapping (multi-echo spin echo). T2 values in the nucleus pulposus (NP, n = 350) and anulus fibrosus (AF, n = 700) were obtained. Differences in T2 values between sexes and anatomic level were evaluated, and linear correlation analysis of T2 values versus degenerative grade was conducted. Findings Cervical IVDs of healthy young adults were commonly determined to be at Pfirrmann grades I and II. T2 values of NPs were significantly higher than those of AF at all anatomic levels (P<0.000). The NP, anterior AF and posterior AF values did not differ significantly between genders at the same anatomic level (P>0.05). T2 values decreased linearly with degenerative grade. Linear correlation analysis revealed a strong negative association between the Pfirrmann grade and the T2 values of the NP (P = 0.000) but not the T2 values of the AF (P = 0.854). However, non-degenerated discs (Pfirrmann grades I and II) showed a wide range of T2 relaxation time. T2 values according to disc degeneration level classification were as follows: grade I (>62.03 ms), grade II (54.60–62.03 ms), grade III (<54.60 ms). Conclusions T2 quantitation provides a more sensitive and robust approach for detecting and characterizing the early stage of cervical IVD degeneration and to create a reliable quantitative in healthy young adults. PMID:24498384

Quantitative T2 magnetic resonance imaging compared to morphological grading of the early cervical intervertebral disc degeneration: an evaluation approach in asymptomatic young adults.

PubMed

Chen, Chun; Huang, Minghua; Han, Zhihua; Shao, Lixin; Xie, Yan; Wu, Jianhong; Zhang, Yan; Xin, Hongkui; Ren, Aijun; Guo, Yong; Wang, Deli; He, Qing; Ruan, Dike

2014-01-01

The objective of this study was to evaluate the efficacy of quantitative T2 magnetic resonance imaging (MRI) for quantifying early cervical intervertebral disc (IVD) degeneration in asymptomatic young adults by correlating the T2 value with Pfirrmann grade, sex, and anatomic level. Seventy asymptomatic young subjects (34 men and 36 women; mean age, 22.80±2.11 yr; range, 18-25 years) underwent 3.0-T MRI to obtain morphological data (one T1-fast spin echo (FSE) and three-plane T2-FSE, used to assign a Pfirrmann grade (I-V)) and for T2 mapping (multi-echo spin echo). T2 values in the nucleus pulposus (NP, n = 350) and anulus fibrosus (AF, n = 700) were obtained. Differences in T2 values between sexes and anatomic level were evaluated, and linear correlation analysis of T2 values versus degenerative grade was conducted. Cervical IVDs of healthy young adults were commonly determined to be at Pfirrmann grades I and II. T2 values of NPs were significantly higher than those of AF at all anatomic levels (P<0.000). The NP, anterior AF and posterior AF values did not differ significantly between genders at the same anatomic level (P>0.05). T2 values decreased linearly with degenerative grade. Linear correlation analysis revealed a strong negative association between the Pfirrmann grade and the T2 values of the NP (P = 0.000) but not the T2 values of the AF (P = 0.854). However, non-degenerated discs (Pfirrmann grades I and II) showed a wide range of T2 relaxation time. T2 values according to disc degeneration level classification were as follows: grade I (>62.03 ms), grade II (54.60-62.03 ms), grade III (<54.60 ms). T2 quantitation provides a more sensitive and robust approach for detecting and characterizing the early stage of cervical IVD degeneration and to create a reliable quantitative in healthy young adults.

In Vitro Characterization of a Stem-Cell-Seeded Triple-Interpenetrating-Network Hydrogel for Functional Regeneration of the Nucleus Pulposus

PubMed Central

Smith, Lachlan J.; Gorth, Deborah J.; Showalter, Brent L.; Chiaro, Joseph A.; Beattie, Elizabeth E.; Elliott, Dawn M.; Mauck, Robert L.; Chen, Weiliam

2014-01-01

Intervertebral disc degeneration is implicated as a major cause of low-back pain. There is a pressing need for new regenerative therapies for disc degeneration that restore native tissue structure and mechanical function. To that end we investigated the therapeutic potential of an injectable, triple-interpenetrating-network hydrogel comprised of dextran, chitosan, and teleostean, for functional regeneration of the nucleus pulposus (NP) of the intervertebral disc in a series of biomechanical, cytotoxicity, and tissue engineering studies. Biomechanical properties were evaluated as a function of gelation time, with the hydrogel reaching ∼90% of steady-state aggregate modulus within 10 h. Hydrogel mechanical properties evaluated in confined and unconfined compression were comparable to native human NP properties. To confirm containment within the disc under physiological loading, toluidine-blue-labeled hydrogel was injected into human cadaveric spine segments after creation of a nucleotomy defect, and the segments were subjected to 10,000 cycles of loading. Gross analysis demonstrated no implant extrusion, and further, that the hydrogel interdigitated well with native NP. Constructs were next surface-seeded with NP cells and cultured for 14 days, confirming lack of hydrogel cytotoxicity, with the hydrogel maintaining NP cell viability and promoting proliferation. Next, to evaluate the potential of the hydrogel to support cell-mediated matrix production, constructs were seeded with mesenchymal stem cells (MSCs) and cultured under prochondrogenic conditions for up to 42 days. Importantly, the hydrogel maintained MSC viability and promoted proliferation, as evidenced by increasing DNA content with culture duration. MSCs differentiated along a chondrogenic lineage, evidenced by upregulation of aggrecan and collagen II mRNA, and increased GAG and collagen content, and mechanical properties with increasing culture duration. Collectively, these results establish the therapeutic potential of this novel hydrogel for functional regeneration of the NP. Future work will confirm the ability of this hydrogel to normalize the mechanical stability of cadaveric human motion segments, and advance the material toward human translation using preclinical large-animal models. PMID:24410394

Therapeutic effects of naringin on degenerative human nucleus pulposus cells for discogenic low back pain.

PubMed

Li, Nianhu; Whitaker, Camden; Xu, Zhanwang; Heggeness, Michael; Yang, Shang-You

2016-10-01

Over half the population of the world will suffer from moderate or severe low back pain (LBP) during their life span. Studies have shown that naringin, a major flavonoid in grapefruit and an active compound extracted from a Chinese herbal medicine (Rhizoma Drynariae) possesses many pharmacological effects. The aim of this study was to evaluate the influence of naringin on the growth of degenerative human nucleus pulposus (NP) cells, and its repair effects on protein and gene expressions of the cells. This was an in vitro investigation of the human NP cells isolated from degenerated intervertebral discs that were interacted with various concentrated of naringin. This study was exempted by the institutional Human Subjects Committee-2, University of Kansas School of Medicine-Wichita. Degenerative human NP cells were isolated from intervertebral discs of patients with discogenic LBP and cultured at 37°C with 5% CO 2 . The proliferation of NP cells was determined following treatment with various concentrations of naringin. The protein expressions of tumor necrosis factor-α (TNF-α) and Bone morphogenetic protein 2 (BMP-2) were tested using enzyme-linked immunosorbent assay. Aggrecan and type II collagen levels were measured by immunohistological staining. Further examination of the gene expression of aggrecan, Sox6, and MMP3 was performed after intervention with naringin for 3 days. The human NP cells were successfully propagated in culture and stained positive with toluidine blue staining. Naringin effectively enhanced the cell proliferation at an optimal concentration of 20 µg/mL. Naringin treatment resulted in significant inhibition of TNF-α, but elevated protein expressions of BMP-2, collagen II, and aggrecan. Naringin also increased disc matrix gene activity including aggrecan and Sox6, and decreased the gene expression of MMP3. Naringin effectively promotes the proliferation of degenerative human NP cells and improves the recuperation of the cells from degeneration by increasing expression of aggrecan, BMP-2, and Sox6 while inhibiting the expression of TNF-α and MMP3. This study suggests that naringin may represent an alternative therapeutic agent for disc degeneration. Copyright © 2016 Elsevier Inc. All rights reserved.

Sacroiliac joint dysfunction in patients with herniated lumbar disc: a cross-sectional study.

PubMed

Madani, Seyed Pezhman; Dadian, Mohammad; Firouznia, Keykavous; Alalawi, Salah

2013-01-01

To determine the relative frequency of sacroiliac joint dysfunction in a sample of patients with image proven lumbar disc herniation. A single group cross-sectional study was conducted in a three year period from 2007 in an outpatient clinic at a university hospital. Overall, 202 patients aged more than or equal to 18 years with image proven herniated lumbar disc and with physical findings suggestive of lumbosacral root irritation were included. Overall, 146 (72.3%) participants had sacroiliac joint dysfunction. The dysfunction was significantly more prevalent in females (p< 0.001, adjusted OR=2.46, 95% CI=1.00 to 6.03), patients with recurrent pain (p< 0.005, adjusted OR=2.33 with 95% CI=1.10 to 4.89) and patients with positive straight leg raising provocative test (p< 0.0001, adjusted OR=5.07, 95% CI=2.37 to 10.85). There was no significant relationship between the prevalence of SIJD, and working hours, duration of low back pain, or body mass index. Sacroiliac joint dysfunction is a significant pathogenic factor with high possibility of occurrence in low back pain. Thus, regardless of intervertebral disc pathology, sacroiliac joint dysfunction must be considered in clinical decision making.

Comparative Study Between M6-C and Mobi-C Cervical Artificial Disc Replacement: Biomechanical Outcomes and Comparison with Normative Data.

PubMed

Pham, My; Phan, Kevin; Teng, Ian; Mobbs, Ralph J

2018-05-01

Cervical spondylosis affects a huge proportion of the middle-aged population. Degenerative changes can occur in multiple regions of the cervical spine typically affecting the joints, intervertebral discs and endplates. These changes lead to compression of adjacent nervous structures, which results in radiculopathic and myelopathic pain. Various treatment modalities are currently available with non-surgical approaches the initial go to if there is no symptomatic cord compression. Anterior cervical discectomy and fusion, or arthroplasty are the two common surgical approaches if non-surgical treatments fail to relieve symptoms of the patients or there are signs of central cord compression. However, studies have shown that there is an increased risk of adjacent segment disease related to fusion. Cervical disc arthroplasty aims to restore normal range of motion (ROM) in patients with pain and disability due to degenerative disc disease resistant to conservative care. Two common disc prostheses used include M6-C and Mobi-C. Both prostheses comprise a mobile polymer segment sandwiched between two metal endplates with mechanisms resembling an actual intervertebral disc. This study aims to compare the kinematics associated with these prostheses, against the normal range of motion in the non-degenerative population. Patients who underwent M6-C or Mobi-C disc replacements by the senior author from 2012 to 2015 were identified at a single tertiary institution. Routine 3-month postoperative lateral radiographs were analyzed for flexion and extension ROM angles at the involved vertebral level by two independent authors. Data was compared to previous published studies investigating cervical spine ROM of asymptomatic patients. There was no statistical significance in the difference of overall flexion range between M6-C and Mobi-C prostheses. However, overall range of extension of Mobi-C was greater compared to M6-C (P = 0.028). At C 5-6 , the range of flexion for both implants were similar but lesser compared to asymptomatic patients (P < 0.001). Range of extension was greater in the Mobi-C group (14.2° ± 5.1°) compared to the M6-C (7.3° ± 4.6°) (P = 0.0009). At C 6-7 , there were no statistical differences in both range of flexion and extension between the two prostheses and asymptomatic patients (P > 0.05). The early results regarding restoration of ROM following cervical arthroplasty using either M6-C or Mobi-C prosthesis are encouraging. Long-term follow-up studies are necessary to observe the change in ROM over time with physiological loading and wear patterns. © 2018 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

Magnetic resonance imaging after exposure to microgravity

NASA Technical Reports Server (NTRS)

Leblanc, Adrian

1993-01-01

A number of physiological changes were demonstrated in bone, muscle, and blood from exposure of humans and animals to microgravity. Determining mechanisms and the development of effective countermeasures for long-duration space missions is an important NASA goal. Historically, NASA has had to rely on tape measures, x-ray, and metabolic balance studies with collection of excreta and blood specimens to obtain this information. The development of magnetic resonance imaging (MRI) offers the possibility of greatly extending these early studies in ways not previously possible; MRI is also non-invasive and safe; i.e., no radiation exposure. MRI provides both superb anatomical images for volume measurements of individual structures and quantification of chemical/physical changes induced in the examined tissues. This investigation will apply MRI technology to measure muscle, intervertebral disc, and bone marrow changes resulting from exposure to microgravity.

The generation of vertebral segmental patterning in the chick embryo

PubMed Central

Senthinathan, Biruntha; Sousa, Cátia; Tannahill, David; Keynes, Roger

2012-01-01

We have carried out a series of experimental manipulations in the chick embryo to assess whether the notochord, neural tube and spinal nerves influence segmental patterning of the vertebral column. Using Pax1 expression in the somite-derived sclerotomes as a marker for segmentation of the developing intervertebral disc, our results exclude such an influence. In contrast to certain teleost species, where the notochord has been shown to generate segmentation of the vertebral bodies (chordacentra), these experiments indicate that segmental patterning of the avian vertebral column arises autonomously in the somite mesoderm. We suggest that in amniotes, the subdivision of each sclerotome into non-miscible anterior and posterior halves plays a critical role in establishing vertebral segmentation, and in maintaining left/right alignment of the developing vertebral elements at the body midline. PMID:22458512

Diffusion-Weighted MRI Assessment of Adjacent Disc Degeneration After Thoracolumbar Vertebral Fractures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Noriega, David C., E-mail: dcnoriega1970@gmail.com; Marcia, Stefano, E-mail: stemarcia@gmail.com; Ardura, Francisco, E-mail: fardura@ono.com

ObjectiveThe purpose of this study was to assess, by the mean apparent diffusion coefficient (ADC), if a relationship exists between disc ADC and MR findings of adjacent disc degeneration after thoracolumbar fractures treated by anatomic reduction using vertebral augmentation (VAP).Materials and MethodsTwenty non-consecutive patients (mean age 50.7 years; range 45–56) treated because of vertebral fractures, were included in this study. There were 10 A3.1 and 10 A1.2 fractures (AO classification). Surgical treatment using VAP was applied in 14 cases, and conservative in 6 patients. MRI T2-weighted images and mapping of apparent diffusion coefficient (ADC) of the intervertebral disc adjacent to themore » fractured segment were performed after a mean follow-up of 32 months. A total of 60 discs, 3 per patient, were analysed: infra-adjacent, supra-adjacent and a control disc one level above the supra-adjacent.ResultsNo differences between patients surgically treated and those following a conservative protocol regarding the average ADC values obtained in the 20 control discs analysed were found. Considering all discs, average ADC in the supra-adjacent level was lower than in the infra-adjacent (1.35 ± 0.12 vs. 1.53 ± 0.06; p < 0.001). Average ADC values of the discs used as a control were similar to those of the infra-adjacent level (1.54 ± 0.06). Compared to surgically treated patients, discs at the supra-adjacent fracture level showed statistically significant lower values in cases treated conservatively (p < 0.001). The variation in the delay of surgery had no influence on the average values of ADC at any of the measured levels.ConclusionsADC measurements of the supra-adjacent discs after a mean follow-up of 32 months following thoracolumbar fractures, showed that restoration of the vertebral collapse by minimally invasive VAP prevents posttraumatic disc degeneration.« less

Intervertebral disc segmentation in MR images with 3D convolutional networks

NASA Astrophysics Data System (ADS)

Korez, Robert; Ibragimov, Bulat; Likar, Boštjan; Pernuš, Franjo; Vrtovec, Tomaž

2017-02-01

The vertebral column is a complex anatomical construct, composed of vertebrae and intervertebral discs (IVDs) supported by ligaments and muscles. During life, all components undergo degenerative changes, which may in some cases cause severe, chronic and debilitating low back pain. The main diagnostic challenge is to locate the pain generator, and degenerated IVDs have been identified to act as such. Accurate and robust segmentation of IVDs is therefore a prerequisite for computer-aided diagnosis and quantification of IVD degeneration, and can be also used for computer-assisted planning and simulation in spinal surgery. In this paper, we present a novel fully automated framework for supervised segmentation of IVDs from three-dimensional (3D) magnetic resonance (MR) spine images. By considering global intensity appearance and local shape information, a landmark-based approach is first used for the detection of IVDs in the observed image, which then initializes the segmentation of IVDs by coupling deformable models with convolutional networks (ConvNets). For this purpose, a 3D ConvNet architecture was designed that learns rich high-level appearance representations from a training repository of IVDs, and then generates spatial IVD probability maps that guide deformable models towards IVD boundaries. By applying the proposed framework to 15 3D MR spine images containing 105 IVDs, quantitative comparison of the obtained against reference IVD segmentations yielded an overall mean Dice coefficient of 92.8%, mean symmetric surface distance of 0.4 mm and Hausdorff surface distance of 3.7 mm.

[Three dimensional finite element model of a modified posterior cervical single open-door laminoplasty].

PubMed

Wang, Q; Yang, Y; Fei, Q; Li, D; Li, J J; Meng, H; Su, N; Fan, Z H; Wang, B Q

2017-06-06

Objective: To build a three-dimensional finite element models of a modified posterior cervical single open-door laminoplasty with short-segmental lateral mass screws fusion. Methods: The C(2)-C(7) segmental data were obtained from computed tomography (CT) scans of a male patient with cervical spondylotic myelopathy and spinal stenosis.Three-dimensional finite element models of a modified cervical single open-door laminoplasty (before and after surgery) were constructed by the combination of software package MIMICS, Geomagic and ABAQUS.The models were composed of bony vertebrae, articulating facets, intervertebral disc and associated ligaments.The loads of moments 1.5Nm at different directions (flexion, extension, lateral bending and axial rotation)were applied at preoperative model to calculate intersegmental ranges of motion.The results were compared with the previous studies to verify the validation of the models. Results: Three-dimensional finite element models of the modified cervical single open- door laminoplasty had 102258 elements (preoperative model) and 161 892 elements (postoperative model) respectively, including C(2-7) six bony vertebraes, C(2-3)-C(6-7) five intervertebral disc, main ligaments and lateral mass screws.The intersegmental responses at the preoperative model under the loads of moments 1.5 Nm at different directions were similar to the previous published data. Conclusion: Three-dimensional finite element models of the modified cervical single open- door laminoplasty were successfully established and had a good biological fidelity, which can be used for further study.

Low level light therapy modulates inflammatory mediators secreted by human annulus fibrosus cells during intervertebral disc degeneration in vitro.

PubMed

Hwang, Min Ho; Shin, Jae Hee; Kim, Kyoung Soo; Yoo, Chang Min; Jo, Ga Eun; Kim, Joo Han; Choi, Hyuk

2015-01-01

Intervertebral disc degeneration (IVD) is one of the important causes of low back pain and is associated with inflammation induced by interaction between macrophages and the human annulus fibrosus (AF) cells. Low-level light therapy (LLLT) has been widely known to regulate inflammatory reaction. However, the effect of LLLT on macrophage-mediated inflammation in the AF cells has not been studied till date. The aim of this study is to mimic the inflammatory microenvironment and to investigate the anti-inflammatory effect of LLLT at a range of wavelengths (405, 532 and 650 nm) on the AF treated with macrophage-like THP-1 cells conditioned medium (MCM) containing proinflammatory cytokines and chemokines (interleukin-1beta, tumor necrosis factor-alpha, interleukin-6 and 8). We observed that AF cells exposed to MCM secrete significantly higher concentrations of IL-6, IL-8, IL-1β and TNF-α. LLLT markedly inhibited secretion of IL-6 at 405 nm in a time-dependent manner. Level of IL-8 was significantly decreased at all wavelengths in a time-dependent manner. We showed that MCM can induce the inflammatory microenvironment in AF cells and LLLT selectively suppressed IL-6 and 8 levels. The results indicate that LLLT is a potential method of IVD treatment and provide insights into further investigation of its anti-inflammation effect on IVD. © 2015 The American Society of Photobiology.

Postoperative computed tomography and low-field magnetic resonance imaging findings in dogs with degenerative lumbosacral stenosis treated by dorsal laminectomy.

PubMed

Rapp, Martin; Ley, Charles J; Hansson, Kerstin; Sjöström, Lennart

2017-03-20

To describe postoperative computed tomography (CT) and magnetic resonance imaging (MRI) findings in dogs with degenerative lumbosacral stenosis (DLSS) treated by dorsal laminectomy and partial discectomy. Prospective clinical case study of dogs diagnosed with and treated for DLSS. Surgical and clinical findings were described. Computed tomography and low field MRI findings pre- and postoperatively were described and graded. Clinical, CT and MRI examinations were performed four to 18 months after surgery. Eleven of 13 dogs were clinically improved and two dogs had unchanged clinical status postoperatively despite imaging signs of neural compression. Vacuum phenomenon, spondylosis, sclerosis of the seventh lumbar (L7) and first sacral (S1) vertebrae endplates and lumbosacral intervertebral joint osteoarthritis became more frequent in postoperative CT images. Postoperative MRI showed mild disc extrusions in five cases, and in all cases contrast enhancing non-discal tissue was present. All cases showed contrast enhancement of the L7 spinal nerves both pre- and postoperatively and seven had contrast enhancement of the lumbosacral intervertebral joints and paraspinal tissue postoperatively. Articular process fractures or fissures were noted in four dogs. The study indicates that imaging signs of neural compression are common after DLSS surgery, even in dogs that have clinical improvement. Contrast enhancement of spinal nerves and soft tissues around the region of disc herniation is common both pre- and postoperatively and thus are unreliable criteria for identifying complications of the DLSS surgery.

Correlation of matrix metalloproteinase (MMP)-1, -2, -3, and -9 expressions with demographic and radiological features in primary lumbar intervertebral disc disease.

PubMed

Basaran, Recep; Senol, Mehmet; Ozkanli, Seyma; Efendioglu, Mustafa; Kaner, Tuncay

2017-07-01

Degeneration of IVD is a progressive and irreversible process and can be evaluated with immunohistochemical examination or radiological grading. MMPs are a family of proteolytic enzymes and involved in the degradation of the matrix components of the IVD. We aimed to compare MMP-1, -2, -3, and -9 expressions with demographic features, visual analogue scale (VAS), Oswestry Disability Index (ODI) and radiological (MRI) grades. The study involved 60 participants. We recorded data about age, complaint, radiological imaging, expression levels of MMP-1, -2, -3, and -9, ODI and VAS for back pain retrospectively. Intervertebral disc degeneration was graded on a 0-5 scale according to the Pfirrmann classification. As a result of the study, the median age was 52.09±12.74years. There were statistical significances between age and MMP-1, and MMP-2. There was a close correlation between grade and MMP-9. We found correlation between the VAS and the MMP-9 expression. In addition, there was relationship between expression of MMP-2 and MMP-1, MMP-3, MMP-9. In conclusion, the expressions of MMP-1 and -2 are increased with aging. There was no relationship between radiological evaluation of IVDD and aging. Increased expression of MMPs affected IVDD positively. The relationship with MMPs is not explained. This study adds to our understanding of the interaction between MMPs and IVDD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Increased Risk for Adhesive Capsulitis of the Shoulder following Cervical Disc Surgery.

PubMed

Kang, Jiunn-Horng; Lin, Herng-Ching; Tsai, Ming-Chieh; Chung, Shiu-Dong

2016-05-27

Shoulder problems are common in patients with a cervical herniated intervertebral disc (HIVD). This study aimed to explore the incidence and risk of shoulder capsulitis/tendonitis following cervical HIVD surgery. We used data from the Taiwan "Longitudinal Health Insurance Database". We identified all patients who were hospitalized with a diagnosis of displacement of a cervical HIVD and who underwent cervical surgery (n = 1625). We selected 8125 patients who received cervical HIVD conservative therapy only as the comparison group matched with study patients. We individually tracked these sampled patients for 6 months to identify all patients who received a diagnosis of shoulder tendonitis/capsulitis. We found that incidence rates of shoulder tendonitis/capsulitis during the 6-month follow-up period were 3.69 (95% CI: 2.49~5.27) per 100 person-years for the study group and 2.33 (95% CI: 1.89~2.86) per 100 person-years for the comparison group. Cox proportional hazard regressions showed that the adjusted hazard ratio for shoulder tendonitis/capsulitis among patients who underwent cervical disc surgery was 1.66 (95% CI = 1.09~2.53) when compared to comparison group. We concluded that patients who underwent surgery for a cervical HIVD had a significantly higher risk of developing shoulder capsulitis/tendonitis in 6 months follow-up compared to patients who received cervical HIVD conservative therapy only.

Assessment of mechanical properties of isolated bovine intervertebral discs from multi-parametric magnetic resonance imaging.

PubMed

Recuerda, Maximilien; Périé, Delphine; Gilbert, Guillaume; Beaudoin, Gilles

2012-10-12

The treatment planning of spine pathologies requires information on the rigidity and permeability of the intervertebral discs (IVDs). Magnetic resonance imaging (MRI) offers great potential as a sensitive and non-invasive technique for describing the mechanical properties of IVDs. However, the literature reported small correlation coefficients between mechanical properties and MRI parameters. Our hypothesis is that the compressive modulus and the permeability of the IVD can be predicted by a linear combination of MRI parameters. Sixty IVDs were harvested from bovine tails, and randomly separated in four groups (in-situ, digested-6h, digested-18h, digested-24h). Multi-parametric MRI acquisitions were used to quantify the relaxation times T1 and T2, the magnetization transfer ratio MTR, the apparent diffusion coefficient ADC and the fractional anisotropy FA. Unconfined compression, confined compression and direct permeability measurements were performed to quantify the compressive moduli and the hydraulic permeabilities. Differences between groups were evaluated from a one way ANOVA. Multi linear regressions were performed between dependent mechanical properties and independent MRI parameters to verify our hypothesis. A principal component analysis was used to convert the set of possibly correlated variables into a set of linearly uncorrelated variables. Agglomerative Hierarchical Clustering was performed on the 3 principal components. Multilinear regressions showed that 45 to 80% of the Young's modulus E, the aggregate modulus in absence of deformation HA0, the radial permeability kr and the axial permeability in absence of deformation k0 can be explained by the MRI parameters within both the nucleus pulposus and the annulus pulposus. The principal component analysis reduced our variables to two principal components with a cumulative variability of 52-65%, which increased to 70-82% when considering the third principal component. The dendograms showed a natural division into four clusters for the nucleus pulposus and into three or four clusters for the annulus fibrosus. The compressive moduli and the permeabilities of isolated IVDs can be assessed mostly by MT and diffusion sequences. However, the relationships have to be improved with the inclusion of MRI parameters more sensitive to IVD degeneration. Before the use of this technique to quantify the mechanical properties of IVDs in vivo on patients suffering from various diseases, the relationships have to be defined for each degeneration state of the tissue that mimics the pathology. Our MRI protocol associated to principal component analysis and agglomerative hierarchical clustering are promising tools to classify the degenerated intervertebral discs and further find biomarkers and predictive factors of the evolution of the pathologies.

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

PubMed

Dudli, Stefan; Liebenberg, Ellen; Magnitsky, Sergey; Miller, Steve; Demir-Deviren, Sibel; Lotz, Jeffrey C

2016-08-01

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

Evaluation of Water Content in Lumbar Intervertebral Discs and Facet Joints Before and After Physiological Loading Using T2 Mapping MRI.

PubMed

Yamabe, Daisuke; Murakami, Hideki; Chokan, Kou; Endo, Hirooki; Oikawa, Ryosuke; Sawamura, Shoitsu; Doita, Minoru

2017-12-15

T2 mapping was used to quantify the water content of lumbar spine intervertebral discs (IVDs) and facet joints before and after physiological loading. The aim of this study was to clarify the interaction between lumbar spine IVD and facet joints as load-bearing structures by measuring the water content of their matrix after physiological loading using T2 mapping magnetic resonance imaging (MRI). To date, few reports have functionally evaluated lumbar spine IVD and facet joints, and their interaction in vivo. T2 mapping may help detect changes in the water content of IVD and articular cartilage of facet joints before and after physiological loading, thereby enabling the evaluation of changes in interacted water retention between IVD and facet joints. Twenty asymptomatic volunteers (10 female and 10 male volunteers; mean age, 19.3 years; age range, 19-20 years) underwent MRI before and after physiological loading such as lumbar flexion, extension, and rotation. Each IVD from L1/2 to L5/S1 was sliced at center of the disc space, and the T2 value was measured at the nucleus pulposus (NP), anterior annulus fibrosus (AF), posterior AF, and bilateral facet joints. In the NP, T2 values significantly decreased after exercise at every lumbar spinal level. In the anterior AF, there were no significant differences in T2 values at any level. In the posterior AF, T2 values significantly increased only at L4/5. In the bilateral facet joints, T2 values significantly decreased after exercise at every level. There was a significant decrease in the water content of facet joints and the NP at every lumbar spinal level after dynamic loading by physical lumbar exercise. These changes appear to play an important and interactional role in the maintenance of the interstitial matrix in the IVD NP and cartilage in the facet joint. 3.

Analysis of the spinal nerve roots in relation to the adjacent vertebral bodies with respect to a posterolateral vertebral body replacement procedure.

PubMed

Awwad, Waleed; Bourget-Murray, Jonathan; Zeiadin, Nadil; Mejia, Juan P; Steffen, Thomas; Algarni, Abdulrahman D; Alsaleh, Khalid; Ouellet, Jean; Weber, Michael; Jarzem, Peter F

2017-01-01

This study aims to improve the understanding of the anatomic variations along the thoracic and lumbar spine encountered during an all-posterior vertebrectomy, and reconstruction procedure. This information will help improve our understanding of human spine anatomy and will allow better planning for a vertebral body replacement (VBR) through either a transpedicular or costotransversectomy approach. The major challenge to a total posterior approach vertebrectomy and VBR in the thoracolumbar spine lies in the preservation of important neural structures. This was a retrospective analysis. Hundred normal magnetic resonance imaging (MRI) spinal studies (T1-L5) on sagittal T2-weighted MRI images were studied to quantify: (1) mid-sagittal vertebral body (VB) dimensions (anterior, midline, and posterior VB height), (2) midline VB and associated intervertebral discs height, (3) mean distance between adjacent spinal nerve roots (DNN) and mean distance between the inferior endplate of the superior vertebrae to its respective spinal nerve root (DNE), and (4) posterior approach expansion ratio (PAER). (1) The mean anterior VB height gradually increased craniocaudally from T1 to L5. The mean midline and posterior VB height showed a similar pattern up to L2. Mean posterior VB height was larger than the mean anterior VB height from T1 to L2, consistent with anterior wedging, and then measured less than the mean anterior VB height, indicating posterior wedging. (2) Midline VB and intervertebral disc height gradually increased from T1 to L4. (3) DNN and DNE were similar, whereby they gradually increased from T1 to L3. (5) Mean PAER varied between 1.69 (T12) and 2.27 (L5) depending on anatomic level. The dimensions of the thoracic and lumbar vertebrae and discs vary greatly. Thus, any attempt at carrying out a VBR from a posterior approach should take into account the specifications at each spinal level.

Expression and functional roles of estrogen receptor GPR30 in human intervertebral disc.

PubMed

Wei, Aiqun; Shen, Bojiang; Williams, Lisa A; Bhargav, Divya; Yan, Feng; Chong, Beng H; Diwan, Ashish D

2016-04-01

Estrogen withdrawal, a characteristic of female aging, is associated with age-related intervertebral disc (IVD) degeneration. The function of estrogen is mediated by two classic nuclear receptors, estrogen receptor (ER)-α and -β, and a membrane bound G-protein-coupled receptor 30 (GPR30). To date, the expression and function of GPR30 in human spine is poorly understood. This study aimed to evaluate GPR30 expression in IVD, and its role in estrogen-related regulation of proliferation and apoptosis of disc nucleus pulposus (NP) cells. GPR30 expression was examined in 30 human adult NP and 9 fetal IVD. Results showed that GPR30 was expressed in NP cells at both mRNA and protein levels. In human fetal IVD, GPR30 protein was expressed in the NP at 12-14 weeks gestation, but was undetectable at 8-11 weeks. The effect of 17β-estradiol (E2) on GPR30-mediated proliferation and interleukin-1β (IL-1β)-induced apoptosis of NP cells was investigated. Cultured NP cells were treated with or without E2, GPR30 antagonist G36, and ER antagonist ICI 182,780. NP cell viability was tested by MTS assay. Apoptosis was determined by flow cytometry using fluorescence labeled annexin-V, TUNEL assay and immumnocytochemical staining of activated caspase-3. E2 enhanced cell proliferation and prevented IL-1β-induced cell death, but the effect was partially blocked by G36 and completely abrogated by a combination of ICI 182,780 and G36. This study demonstrates that GPR30 is expressed in human IVD to transmit signals triggering E2-induced NP cell proliferation and protecting against IL-1β-induced apoptosis. The effects of E2 on NP cells require both GPR30 and classic estrogen receptors. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cytotoxic Effects of the Radiocontrast Agent Iotrolan and Anesthetic Agents Bupivacaine and Lidocaine in Three-Dimensional Cultures of Human Intervertebral Disc Nucleus Pulposus Cells: Identification of the Apoptotic Pathways

PubMed Central

Iwasaki, Koji; Sudo, Hideki; Yamada, Katsuhisa; Ito, Manabu; Iwasaki, Norimasa

2014-01-01

Background Discography and discoblock are imaging procedures used to diagnose discogenic low back pain. Although needle puncture of the intervertebral disc (IVD) itself induces disc degeneration, the agents used in these procedures may also have harmful effects on IVD cells. The purpose of this study was to analyze whether radiocontrast agents and local anesthetic agents have detrimental effects on human nucleus pulposus (NP) cells. Methods Healthy human NP cells were cultured for 7 days in three-dimensional (3D) cell–alginate bead composites, and were then exposed to clinically relevant doses of a radiocontrast agent (iotrolan) or local anesthetic (lidocaine or bupivacaine). Cell viability and apoptosis were measured by confocal microscopy and flow cytometry. On the basis of caspase expression profiles, the apoptotic pathways activated by the agents were identified by Western blot analysis. Results The radiocontrast agent iotrolan did not affect NP cell viability or induce apoptosis. In contrast, both the anesthetic agents significantly decreased cell viability and increased the apoptotic cell number in a time- and dose-dependent manner. After 120 min, 2% lidocaine and 0.5% bupivacaine decreased percent live cells to 13% and 10%, respectively (p<0.05). The number of apoptotic cells was doubled by increasing lidocaine dosage from 1% to 2% (23% and 42%) and bupivacaine from 0.25% to 0.50% (25% and 48%) (p<0.05). Western blot analysis revealed that both anesthetic agents upregulated cleaved caspase-3 and caspase-8, whereas only bupivacaine upregulated cleaved caspase-9. Conclusions/Significance The present study demonstrates that iotrolan does not affect the viability of healthy human NP cells. In contrast, the two anesthetic agents commonly used in discography or discoblock may cause extensive damage to IVDs by inducing apoptotic cell death. PMID:24642945

Co-culture of Adult Mesenchymal Stem Cells and Nucleus Pulposus Cells in Bilaminar Pellets for Intervertebral Disc Regeneration.

PubMed

Allon, Aliza A; Schneider, Richard A; Lotz, Jeffrey C

2009-01-01

Our goal is to optimize stem cell-based tissue engineering strategies in the context of the intervertebral disc environment. We explored the benefits of co-culturing nucleus pulposus cells (NPC) and adult mesenchymal stem cells (MSC) using a novel spherical bilaminar pellet culture system where one cell type is enclosed in a sphere of the other cell type. Our 3D system provides a structure that exploits embryonic processes such as tissue induction and condensation. We observed a unique phenomenon: the budding of co-culture pellets and the formation of satellite pellets that separate from the main pellet. MSC and NPC co-culture pellets were formed with three different structural organizations. The first had random organization. The other two had bilaminar organization with either MSC inside and NPC outside or NPC inside and MSC outside. By 14 days, all co-culture pellets exhibited budding and spontaneously generated satellite pellets. The satellite pellets were composed of both cell types and, surprisingly, all had the same bilaminar organization with MSC on the inside and NPC on the outside. This organization was independent of the structure of the main pellet that the satellites stemmed from. The main pellets generated satellite pellets that spontaneously organized into a bilaminar structure. This implies that structural organization occurs naturally in this cell culture system and may be inherently favorable for cell-based tissue engineering strategies. The occurrence of budding and the organization of satellite pellets may have important implications for the use of co-culture pellets in cell-based therapies for disc regeneration. From a therapeutic point of view, the generation of satellite pellets may be a beneficial feature that would serve to spread donor cells throughout the host matrix and restore normal matrix composition in a sustainable way, ultimately renewing tissue function.