bluuebunny/crossref_metadata_2025_split huggingface dataset:
Operative Management of Lumbar Disc Herniation with End Plate Modic Changes Necessitates More Definite Procedures
Authors: Cao P. 
Published: May 2014

Introduction Nucleotomy through interlaminar fenestration has been the standard operation for lumbar disc herniation, but it does not always work well in clinical practice. End plate Modic changes are strongly linked with lower back pain, and Modic changes in the end plates of the herniation level may be one reason for the unpredictable result of nucleotomy alone. Studies on more definite surgical procedures for lumbar disc herniation with end plate Modic changes are still rare. To compare the clinical outcomes between two surgical options, nucleotomy alone and nucleotomy with additional posterolateral lumbar interbody fusion (PLIF), for lumbar disc herniation patients with end plate Modic changes, and to testify the hypothesis that end plate Modic change is an indication of interbody fusion for operative management of lumbar disc herniation. Materials and Methods A total of 91 patients who complained about both lower extremity radicular pain and lower back pain (lower back pain more severe than leg pain) were included, and all of them were of single segment disc herniation with Modic changes in the corresponding lumbar degenerative end plates. Of the 91 patients, 47 were treated with nucleotomy alone and 44 were treated with posterolateral lumbar interbody fusion (PLIF) in addition to nucleotomy. They were followed up for at least 2 years. Clinical outcomes were evaluated according to the Japanese Orthopaedic Association (JOA) score and visual analogue scale (VAS) for lower back pain and VAS for lower extremity radicular pain before operation and at each follow-up, and the results before surgery and at 18 months after operation were statistically compared. Results In both the groups, the JOA scores, as well as VAS, for lower back pain significantly improved 18 months after surgery. The improvement rate of JOA score and power of improvement of VAS for lower back pain also showed significant difference between the two groups, being better in nucleotomy with PLIF procedure than in nucleotomy alone procedure. On the contrary, the mean VAS of lower extremity radicular pain showed a significant reduction in both groups at the follow-up of 18 months after operation. However, a significant difference of the power of this improvement between both the groups was not found. Conclusion Operative management of lumbar disc herniation with end plate Modic changes necessitates more definite procedures in addition to nucleotomy. PLIF is a good and reliable option. Disclosure of Interest None declared
Spontaneous Regression of Extruded Cervical Disc Herniation in a 26-Year-Old Woman: A Case Report and Review of the Literature
Authors: Dechun D. , Chunlin T. 
Published: May 2014

Introduction The spontaneous regression of lumbar disc herniation was increasingly documented in the literatures. However, radiographically demonstrated regression of a cervical disc herniation with myelopathic symptoms was relatively rare, because most cases received early surgical intervention as soon as radiological presentation of serious extrusion in cervical vertebrae. Materials and Methods In this article, one case of spontaneous regression of extruded cervical herniated discs was presented. No history of trauma was reported in a 26-year-old woman, with 1-month history of gradual-onset neck pain and upper back pain, and left arm numbness. Magnetic resonance imaging (MRI) of the cervical spine revealed spine seriously compressed at the cervical C5-C6 levels. The patient denied operation and received conservative rehabilitation treatment. Results The disc regressions were correlated with clinical improvement and documented with follow-up MRI studies 6 months later. Nonsurgical conservative observation may be considered an option for treatment of some extruded cervical disc herniations that are likely to regress for very specific and predictable reasons based on thorough understanding of patient's case history and positive signs. It was necessary to take frequent follow-ups and excluded gradual spine lesion. Conclusion Nonsurgical conservative observation may be considered an option for treatment of some extruded cervical disc herniations that are likely to regress for very specific and predictable reasons based on thorough understanding of patient's case history and positive signs. It was necessary to take frequent follow-ups and excluded gradual spine lesion. Disclosure of Interest None declared References Ito T, Yamada M, Ikuta F, et al. Histologic evidence of absorption of sequestration-type herniated disc. Spine 1996;21(2):230–234 Slavin KV, Raja A, Thornton J, Wagner FC Jr. Spontaneous regression of a large lumbar disc herniation: report of an illustrative case. Surg Neurol 2001;56(5):333-336, discussion 337 Mochida K, Komori H, Okawa A, Muneta T, Haro H, Shinomiya K. Regression of cervical disc herniation observed on magnetic resonance images. Spine 1998;23(9):990-995, discussion 996–997 Saal JS, Saal JA, Yurth EF. Nonoperative management of herniated cervical intervertebral disc with radiculopathy. Spine 1996;21(16):1877–1883
Comparison of the Safety Outcomes between Anterior Lumbar Interbody Fusion and Extreme Lateral Interbody Fusion
Authors: Hartl R. , Christensen F. , Korge A. , Lam K. , Vialle E. , Zigler J. , McGuire R. 
Published: May 2014

Introduction This review compares the safety of the interbody fusion procedures anterior lumbar interbody fusion (ALIF) and extreme lateral transpsoas interbody fusion (ELIF) in the treatment of degenerative spinal disorders. ALIF is well established whereas ELIF is a novel procedure. Materials and Methods We performed a systematic literature search in the databases Cochrane (CENTRAL), MEDLINE, EMBASE, and the FDA register. Information was collected on study design, sample size, population, procedure, indication incl. number, and location of levels involved, follow-up (FU) time and adverse events. Moreover, information on conflict of interest and source of funding was captured. Results Of 32 eligible publications, 22 dealt with ELIF, 9 with ALIF, and 1 compared ELIF with ALIF. All of the ELIF studies were case series. The number of patients was 2,165 and 1,379, with a FU time from 45 days to 24 months and 24 months to 5 years for ELIF and ALIF, respectively. The risk to experience certain types of adverse events (e.g., reoperations, hardware failures, DVT, and cardiac) appeared significantly lower for patients undergoing ELIF. Pseudarthrosis was seen in 0.14 and 1.02% of ELIF and ALIF cases, respectively. Neurological complications occurred in 7.62% of ELIF and 9.43% of ALIF cases. [Table: see text] Conclusion ELIF procedures demonstrated a favorable safety outcome compared with ALIF, nonetheless the lack of comparative studies, length of follow-up, and low level of evidence is a limitation of this review. Disclosure of Interest R. Hartl: Conflict with DePuy Synthes, Spine Wave, Brainlab, Lanx F. Christensen: None declared A. Korge: None declared K. Lam: None declared E. Vialle: None declared J. Zigler: None declared R. McGuire: None declared
Elevated VEGF in Degenerative Intervertebral Discs in Rats with Injured Intervertebral Discs of the Caudal Vertebrae
Authors: Sato J. , Sakuma Y. , Yamauchi K. , Orita S. , Kubota G. , Oikawa Y. , Inage K. , Sainoh T. , Fujimoto K. , Takahashi K. , Ohtori S. , Miyagi M. 
Published: May 2014

Introduction Recently, inflammatory cytokines, which are elevated in degenerative intervertebral discs, have been recognized as targets of drug therapy for discogenic back pain. Some reports have shown that the level of vascular endothelial growth factor (VEGF), a protein involved in angiogenesis, is elevated at inflamed sites, and we believed that VEGF could be a target for the treatment of discogenic back pain. Thus, we investigated the presence of VEGF in degenerative intervertebral discs in rats with injured intervertebral discs of the caudal vertebrae. Materials and Methods Forty male rats (age, 8 weeks) were divided into two groups: injured group (intervertebral discs between the fifth and sixth, and sixth and seventh caudal vertebrae were punctured 10 times using a 26G needle) and noninjured group (intact discs). The intervertebral discs were collected at 1, 4, 7, and 14 days after the procedure ( n = 5 from each group at each time point), and quantitative evaluation of VEGF was performed using ELISA. Results The VEGF level was maximum 1 day after the procedure, and then the level gradually decreased. In addition, the VEGF levels during the entire study period were significantly higher in the injured group compared with those in the noninjured group ( p < 0.05). Conclusion In this study, injury to the intervertebral discs resulted in elevated VEGF levels. This finding confirms the increased production of inflammatory cytokines in injured intervertebral discs and indicates that VEGF might be involved in discogenic back pain. Moreover, the presence of elevated VEGF levels during the study period shows that VEGF might be responsible for lingering pain. Anti-VEGF antibodies are already in use in the ophthalmic field. On the basis of the findings in this study, a clinical trial involving the administration of anti-VEGF antibodies into the intervertebral discs for the treatment of low back pain in humans was approved by the review committee in September 2013 and will be performed in the near future. Disclosure of Interest None declared
Effects of Pedicle Screw and Spinous Process Distraction on Adjacent Foramina
Authors: Amor N. , Karas C. 
Published: May 2014

Introduction Surgical advances attempt to alleviate lumbar spinal stenosis, which burdens many people in our aging population. One goal of pedicle screw and spinous process distraction is to decompress the neural foramina of the affected segment. The objective of this study is to evaluate the change in the foraminal size adjacent to the distracted level. Materials and Methods The lumbar spine of a prone cadaveric specimen was exposed. Titanium pedicle screws were placed from L1-L5. A titanium rod spanning only two levels on either side of the spine was fastened down at the caudal end and secured at the cephalad end. The screws were distracted until maximal resistance on the left side was reached and then the cephalad set screw was secured. The same amount of distraction was applied to the right side and secured in the same fashion. A second prone cadaveric specimen was exposed. Titanium screws were instead inserted into the spinous processes at levels L1-L4. The distraction technique described above was used with two predetermined distances (3 mm and 6 mm). A CT scan was obtained before and after distraction at each level. Foraminal openings at the level of distraction as well as the adjacent above and below foramina were measured and analyzed. Results In the pedicle-distraction specimen, there was an overall positive percent change at the level of distraction and an overall negative percent change in the levels above and below. The level of L3-L4 on the right revealed the largest percent change (11.09%) in foramen distraction. The foramen superior to the L2-L3 distraction demonstrated the least amount of change (−9.71%). The spinous process-distraction specimen demonstrated an overall positive percent change at the level of the distraction but not an overall negative change at the adjacent levels. The L1-L2 superior adjacent foramina had negative percent changes at the 3 mm and 6 mm of −2.80% R, −12.52% L and −4.20% R,−15.46% L, respectively. Only the right, 3 mm distraction of the inferior adjacent of L1-L2 showed a negative percent change, the rest were positive changes. The L3-L4 distractions including above and below foramina were positive percent changes. The greatest percent change at L3-L4 for the 6 mm distraction was 43.1% at the level of distraction and 6.35% at the above adjacent level. Conclusion Distraction of the lumbar spine at any level does increase foramen size at that level, but adjacent levels are affected differently depending on the type of distraction. Distraction at the spinous process may be more beneficial particularly in the lower lumbar area. Further studies are necessary to reproduce these results to provide a basis for determining an optimal method for foraminal distraction which minimizes adjacent level stenosis. Disclosure of Interest None declared
Development New Pain Targets in the Genomic Era
Authors: Diatchenko Luda , Fillingim Roger B. , Smith Shad B. , Maixner William 
Published: May 2014

Musculoskeletal pain conditions, such low back pain, are characterized by a report of pain greater than expected based on the results of a standard physical evaluation. The pathophysiology of these conditions is largely unknown, we lack biological markers for accurate diagnosis, and conventional therapeutics have limited effectiveness. Growing evidence suggests that chronic pain conditions are associated with both physical and psychological triggers, which initiate pain amplification and psychological distress; thus, susceptibility is dictated by complex interactions between genetic and environmental factors. Herein, we will review phenotypic and genetic markers of common musculoskeletal pain conditions, selected based on their association with musculoskeletal pain in previous research. The phenotypic markers of greatest interest include measures of pain amplification and “psychological” measures (such as emotional distress, somatic awareness, psychosocial stress, and catastrophizing). Genetic polymorphisms reproducibly linked with musculoskeletal pain are found in genes contributing to serotonergic and adrenergic pathways. Elucidation of the biological mechanisms by which these markers contribute to the perception of pain in these patients will enable the development of novel effective drugs and methodologies that permit better diagnoses and approaches to personalized medicine. Acknowledgments for Grant Support • 1K12DSE022793/PHS HHS/United States • AG033906/AG/NIA NIH HHS/United States • P01 NS045685/NS/NINDS NIH HHS/United States • R01-DE16558/DE/NIDCR NIH HHS/United States • U01-DE017018/DE/NIDCR NIH HHS/United States Disclosure of Interest Substantial shareholders: Attagene, Inc., Algynomics, Inc.; Consultant: Clontech, Inc., Algynomics, Inc.; Officer position: Algynomics, Inc.
Is Low Back Pain a Genetic Problem?
Authors: Karppinen Jaro 
Published: May 2014

Twin studies indicate that the (1) heritability of low back pain (LBP) is considerable varying between 30 and 46% depending on the setting, and (2) disc degeneration (DD) has a strong mediating effect in LBP with 11 to 13% of shared genetic effects. Until now, genetic research in LBP has focused on candidate genes; disease-related single-nucleotide polymorphisms have been found in structural, immune system, and nociception-related proteins. So far, no genome-wide association studies (GWAS) have been published in LBP. GWAS data will undoubtedly increase our knowledge on genetics of LBP. However, GWAS is able to detect only common variants (> 5% MAF) and it is reasonable to expect that rare variants, obtained by whole-genome sequencing, have a role in LBP as well as in other complex disorders. Environmental factors have a significant role in LBP. Epigenetics describes heritable information not encoded in DNA. Different epigenetic mechanisms include such as methylation of cytosines in DNA, posttranslational modifications (mainly acetylation) of histones and microRNAs. Epigenetic regulation has an important role in complex disorders and preliminary evidence indicates that epigenetic mechanisms are important in DD as well. The future of LBP genetics requires first an unambiguous phenotype (mere subjective experience of pain is not enough). Discovery of objective endophenotypes of LBP may clarify the phenotype issue. Second, we need to establish large consortiums with genetic and epigenetic sample collection and systematic assessment of environmental (includes also psychological factors) determinants. Methodologically, bioinformatics will be most likely the rate-limiting step—at least in the beginning. Genetic analyses will most likely shift from common-to-rare variants—covering more extensively also the nonprotein coding area. However, in time, genetic research in LBP will evolve and become more commonplace. Disclosure of Interest None declared References Battié MC, Videman T, Levalahti E, Gill K, Kaprio J. Heritability of low back pain and the role of disc degeneration. Pain 2007;131(3):272–280 Denk F, McMahon SB, Tracey I. Pain vulnerability: a neurobiological perspective. Nat Neurosci 2014;17(2):192–200 Diatchenko L, Fillingim RB, Smith SB, Maixner W. The phenotypic and genetic signatures of common musculoskeletal pain conditions. Nat Rev Rheumatol 2013;9(6):340–350 J Eskola P, Männikkö M, Samartzis D, Karppinen J. Genome-wide association studies of lumbar disc degeneration-are we there yet? Spine J 2014;14(3):479–482 Foulkes T, Wood JN. Pain genes. PLoS Genet 2008;4(7):e1IN1.02086 Livshits G, Popham M, Malkin I, et al. Lumbar disc degeneration and genetic factors are the main risk factors for low back pain in women: the UK Twin Spine Study. Ann Rheum Dis 2011;70(10):1740–1745 Mogil JS. Pain genetics: past, present and future. Trends Genet 2012;28(6):258–266 Näkki A, Battié MC, Kaprio J. Genetics of disc-related disorders: current findings and lessons from other complex diseases. Eur Spine J 2013; July 10 (Epub ahead of print)
Role of Cytokines and Proteases in the Pathogenesis of Intervertebral Disc Degeneration
Authors: Le Maitre Christine L. 
Published: May 2014

The intact intervertebral disc (IVD) is considered an immune-privileged site with no inflammatory cells. Despite the lack of inflammatory cells, the IVD has been shown to be a source of a plethora of cytokines and chemokines, normally associated with inflammation. These cytokines are produced by the nucleus pulpous (NP) and annulus fibrous (AF) of the disc and their expression is increased during disc degeneration together with expression of their receptors. Whereas a plethora of cytokines have been identified during disc degeneration, the main research focus has been toward interleukin 1 (IL-1) and tumor necrosis factor α (TNFα) initially driven by their known roles in osteoarthritis. These cytokines have been shown to regulate several characteristic features of disc degeneration, including increased expression of matrix degrading enzymes: MMPs and ADAMTS, the main proteases produced within the degenerate disc. IL-1 and TNF have also been implicated in the down regulation of normal matrix synthesis, induction of factors which could lead to the ingrowth of blood vessels and nerves, and induction of cellular senescence and apoptosis. However, of these two cytokines, IL-1 appears to be the main regulator of the pathogenic events within the degenerate disc. IL-1 stimulation induces the expression of a plethora of cytokines and chemokines by NP cells and inhibition of IL-1 by the natural inhibitor of IL-1: IL-1Ra in ex vivo tissue explants obliterates all matrix degrading enzyme activity. Recent studies have shown that in a mouse model where the natural inhibitor of IL-1: IL-1Ra is knocked out the mice demonstrated spontaneous degeneration, associated with increased expression of matrix degrading enzymes, thus implicating IL-1 as a causative agent in disc degeneration. This is further supported by the numerous studies which link polymorphisms in the IL-1 gene family to increased risk of IVD degeneration and herniation in humans. This presentation will focus on the current understanding of the role of cytokines and chemokine's in the pathogenesis of disc degeneration and herniation, particularly on their role in regulating protease expression and other characteristic features of degeneration. Furthermore, the involvement of inflammation following herniation will be discussed, providing the distinction between true “inflammation” and “inflammatory cytokine” roles in the pathogenesis of disc degeneration and herniation, and how these can be targeted in therapeutic approaches. Disclosure of Interest None declared
CCN2 Functions as Anti-Inflammatory Molecule in the Intervertebral Disc
Authors: Risbud Makarand V. 
Published: May 2014

The aim of the study was to delineate regulation of CTGF/CCN2 expression by cytokines, IL-1β and TNF-α. In addition, we addressed if CCN2 modulates cytokine action on NP cells. Our studies showed that cytokines suppress CCN2 expression and that this effect was mediated in an NF-κB dependent but MAPK independent fashion. Site-directed mutagenesis and genomic chromatin immunoprecipitation (ChIP) analyses showed that the conserved κB sites located at −93/−86 and −546/−537 bp in the CCN2 promoter interacted with p65/RelA and mediated this suppressive effect of cytokines on CCN2 expression. Concerning role of CCN2 under inflammatory state, it was seen that the treatment of NP cells with IL-1β along with CCN2 blocked the stimulatory effect of IL-1β on MMP-3, ADAMTS5, prolyl hydroxylase 3 and syndecan 4 expression. Furthermore, silencing of CCN2 in human NP cells resulted in increased expression of catabolic genes and inflammatory cytokines such as IL-6, IL-4, and IL-12 as measured by gene expression analysis and cytokine protein array, respectively, under basal state. However, reporter analysis clearly showed that the inhibitory effect of CCN2 on IL-1β was independent of regulation of NF-κB signaling pathway. Using echistatin and VLO4, peptide inhibitors to αvβ3 and α5β1 integrins, we also showed that CCN2 interaction with these integrins was necessary for the inhibition of IL-1β-induced catabolic gene expression. Finally, analysis of human tissues showed a trend of altered expression of these integrins during degeneration. Collective, our results suggest that CCN2 and cytokines may form a functional negative feedback loop in NP cells important in the pathogenesis of disc degeneration. Disclosure of Interest None declared
Schmorl Nodes, Disc Degeneration, and Pain
Authors: Cheung Kenneth M , Samartzis Dino , Mok Florence P. S. , Karppinen Jaro , Luk Keith D. K. , Fong Daniel Y. T. 
Published: May 2014

Schmorl nodes (SNs) of the lumbar spine are an ill-defined entity sometimes referred to as intravertebral disc herniation and by others as end plate irregularities. They are often considered a radiographic curiosity with no clinical consequences. As part of a large-scale population-based study of the Hong Kong Degenerative Disc Disease cohort, sagittal T2-weighted magnetic resonance images of the lumbar spine were analyzed in 2,499 volunteers. SNs were found in 16.4% of the study population, being most common at L1/2 and L2/3 (54.1%). Multivariate logistic regression revealed that males, taller and heavier individuals had an increased likelihood of SN ( p < 0.005), suggesting mechanical factors may play a role in their pathogenesis. On the contrary, SNs were independent of age. Overall presence of SN was associated with disc degeneration ( p < 0.001), and linearly correlated ( R2 = 0.97) with increase in severity of degeneration. SN were particularly associated with severe disc degeneration at L1/2 and L2/3 with 22- to 15-fold increased odds, respectively ( p < 0.0001), but less than 5-fold increased odds ( p < 0.001) were noted in the lower lumbar spine. This presentation will discuss the various radiologic appearances of end plate irregularities that may be considered as SNs and propose a new classification based on morphology. In addition, morphological patterns tend to cluster in a particular manner to suggest different etiological factors may be associated with different subtypes of SNs. The relevance of end plate changes in the etiology of lumbar disc degeneration will also be discussed. Disclosure of Interest None declared