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Finite element models of the intervertebral disc are used to address research questions that cannot be tested through typical experimentation. A disc model requires complex geometry and tissue properties to be accurately defined to mimic the physiological disc. The physiological disc possesses residual strain in the annulus fibrosus (AF) due to osmotic swelling and due to inherently pre‐strained fibers. We developed a disc model with residual contributions due to swelling‐only, and a multigeneration model with residual contributions due to both swelling and AF fiber pre‐strain and validated it against organ‐scale uniaxial, quasi‐static and multiaxial, dynamic mechanical tests. In addition, we demonstrated the models' ability to mimic the opening angle observed following radial incision of bovine discs. Both models were validated against organ‐scale experimental data. While the swelling only model responses were within the experimental 95% confidence interval, the multigeneration model offered outcomes closer to the experimental mean and had a bovine model opening angle within one SD of the experimental mean. The better outcomes for the multigeneration model, which allowed for the inclusion of inherently pre‐strained fibers in AF, is likely due to its uniform fiber contribution throughout the AF. We conclude that the residual contribution of pre‐strained fibers in the AF should be included to best simulate the physiological disc and its behaviors., We validated a disc model with residual contributions due to swelling‐only and a multigeneration model with residual contributions due to both swelling and AF fiber pre‐strain against organ‐scale uniaxial, quasi‐static and multiaxial, dynamic mechanical tests as well as tested the models’ ability to mimic the opening angle observed following radial incision of bovine discs. The swelling only model was within the confidence interval, though the multigeneration model was closer to the experimental mean; the better outcomes for the multigeneration model is likely due to its uniform fiber contribution throughout the AF. We conclude that the residual contribution of pre‐strained fibers in the AF should be included to best simulate the physiological disc and its behaviors.

Noninvasive assessments of intervertebral disc health and degeneration are critical for addressing disc degeneration and low back pain. Magnetic resonance imaging (MRI) is exceptionally sensitive to tissue with high water content, and measurement of the MR transverse relaxation time, T 2, has been applied as a quantitative, continuous, and objective measure of disc degeneration that is linked to the water and matrix composition of the disc. However, T 2 measurement is susceptible to inaccuracies due to Rician noise, T 1 contamination, and stimulated echo effects. These error generators can all be controlled for with proper data collection and fitting methods. The objective of this study was to identify sequence parameters to appropriately acquire MR data and to establish curve fitting methods to accurately calculate disc T 2 in the presence of noise by correcting for Rician noise. To do so, we compared T 2 calculated from the typical monoexponential (MONO) fits and noise corrected exponential (NCEXP) fits. We examined how the selected sequence parameters altered the calculated T 2 in silico and in vivo. Typical MONO fits were frequently poor due to Rician noise, and NCEXP fits were more likely to provide accurate T 2 calculations. NCEXP is particularly less biased and less uncertain at low SNR. This study showed that the NCEXP using sequences with data from 20 echoes out to echo times of ~300 ms is the best method for calculating T 2 of discs. By acquiring signal data out to longer echo times and accounting for Rician noise, the curve fitting is more robust in calculating T 2 despite the noise in the data. This is particularly important when considering degenerate discs or AF tissue because the SNR of these regions is lower.

Nucleotomy is a common surgical procedure and is also performed in ex vivo mechanical testing to model decreased nucleus pulposus (NP) pressurization that occurs with degeneration. Here, we implement novel and noninvasive methods using magnetic resonance imaging (MRI) to study internal 3D annulus fibrosus (AF) deformations after partial nucleotomy and during axial compression by evaluating changes in internal AF deformation at reference loads (50 N) and physiological compressive loads (∼10% strain). One particular advantage of this methodology is that the full 3D disc deformation state, inclusive of both in-plane and out-of-plane deformations, can be quantified through the use of a high-resolution volumetric MR scan sequence and advanced image registration. Intact grade II L3-L4 cadaveric human discs before and after nucleotomy were subjected to identical mechanical testing and imaging protocols. Internal disc deformation fields were calculated by registering MR images captured in each loading state (reference and compressed) and each condition (intact and nucleotomy). Comparisons were drawn between the resulting three deformation states (intact at compressed load, nucleotomy at reference load, nucleotomy at compressed load) with regard to the magnitude of internal strain and direction of internal displacements. Under compressed load, internal AF axial strains averaged −18.5% when intact and −22.5% after nucleotomy. Deformation orientations were significantly altered by nucleotomy and load magnitude. For example, deformations of intact discs oriented in-plane, whereas deformations after nucleotomy oriented axially. For intact discs, in-plane components of displacements under compressive loads oriented radially outward and circumferentially. After nucleotomy, in-plane displacements were oriented radially inward under reference load and were not significantly different from the intact state at compressed loads. Re-establishment of outward displacements after nucleotomy indicates increased axial loading restores the characteristics of internal pressurization. Results may have implications for the recurrence of pain, design of novel therapeutics, or progression of disc degeneration.

The kinematics of the intervertebral disc are defined by six degrees of freedom (DOF): three translations (Tz: axial compression, Tx: lateral shear, and Ty: anterior‐posterior shear) and three rotations (Rz: torsion, Rx: flexion‐extension, and Ry: lateral bending). There is some evidence that the six DOFs are mechanically coupled, such that loading in one DOF affects the mechanics of the other five “off‐axis” DOFs, however, most studies have not controlled and/or measured all six DOFs simultaneously. Additionally, the relationships between disc geometry and disc mechanics are important for evaluation of data from different sized donor and patient discs. The objectives of this study were to quantify the mechanical behavior of the intervertebral disc in all six degrees of freedom (DOFs), measure the coupling between the applied motion in each DOF with the resulting off‐axis motions, and test the hypothesis that disc geometry influences these mechanical behaviors. All off‐axis displacements and rotations were significantly correlated with the applied DOF and were of similar magnitude as physiologically relevant motion, confirming that off‐axis coupling is an important mechanical response. Interestingly, there were pairs of DOFs that were especially strongly coupled: lateral shear (Tx) and lateral bending (Ry), anterior‐posterior shear (Ty) and flexion‐extension (Rx), and compression (Tz) and torsion (Rz). Large off‐axis shears may contribute to injury risk in bending and flexion. In addition, the disc responded to shear (Tx, Ty) and rotational loading (Rx, Ry, and Rz) by increasing in disc height in order to maintain the applied compressive load. Quantifying these mechanical behaviors across all six DOF are critical for designing and testing disc therapies, such as implants and tissue engineered constructs, and also for validating finite element models.

Geometry is an important indicator of disc mechanical function and degeneration. While the geometry and associated degenerative changes in the nucleus pulposus and the annulus fibrosus are well-defined, the geometry of the cartilage endplate (CEP) and its relationship to disc degeneration are unknown. The objectives of this study were to quantify CEP geometry in three dimensions using an MRI FLASH imaging sequence and evaluate relationships between CEP geometry and age, degeneration, spinal level, and overall disc geometry. To do so, we assessed the MRI-based measurements for accuracy and repeatability. Next, we measured CEP geometry across a larger sample set and correlated CEP geometric parameters to age, disc degeneration, level, and disc geometry. The MRI-based measures resulted in thicknesses (0.3-1 mm) that are comparable to prior measurements of CEP thickness. CEP thickness was greatest at the anterior/posterior (A/P) margins and smallest in the center. The CEP A/P thickness, axial area, and lateral width decreased with age but were not related to disc degeneration. Age-related, but not degeneration-related, changes in geometry suggest that the CEP may not follow the progression of disc degeneration. Ultimately, if the CEP undergoes significant geometric changes with aging and if these can be related to low back pain, a clinically feasible translation of the FLASH MRI-based measurement of CEP geometry presented in this study may prove a useful diagnostic tool. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1410-1417, 2016.

Here we develop a three-dimensional analytic model for MR image contrast of collagen lamellae in the annulus fibrosus of the intervertebral disc of the spine, based on the dependence of the MRI signal on collagen fiber orientation. High-resolution MRI scans were performed at 1.5 and 7 T on intact whole disc specimens from ovine, bovine, and human spines. An analytic model that approximates the three-dimensional curvature of the disc lamellae was developed to explain inter-lamellar contrast and intensity variations in the annulus. The model is based on the known anisotropic dipolar relaxation of water in tissues with ordered collagen. Simulated MRI data were generated that reproduced many features of the actual MRI data. The calculated inter-lamellar image contrast demonstrated a strong dependence on the collagen fiber angle and on the circumferential location within the annulus. This analytic model may be useful for interpreting MR images of the disc and for predicting experimental conditions that will optimize MR image contrast in the annulus fibrosus.

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. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1264-1273, 2016.

Biomimetic proteoglycans (BPGs) were designed to mimic the three-dimensional (3D) bottlebrush architecture of natural extracellular matrix (ECM) proteoglycans, such as aggrecan. BPGs were synthesized by grafting native chondroitin sulfate bristles onto a synthetic poly(acrylic acid) core to form BPGs at a molecular weight of approximately ∼1.6 MDa. The aggrecan mimics were characterized chemically, physically, and structurally, confirming the 3D bottlebrush architecture as well as a level of water uptake, which is greater than that of the natural proteoglycan, aggrecan. Aggrecan mimics were cytocompatible at physiological concentrations. Fluorescently labeled BPGs were injected into the nucleus pulposus of the intervertebral disc ex vivo and were retained in tissue before and after static loading and equilibrium conditioning. BPGs infiltrated the tissue, distributed and integrated with the ECM on a molecular scale, in the absence of a bolus, thus demonstrating a new molecular approach to tissue repair: molecular matrix engineering. Molecular matrix engineering may compliment or offer an acellular alternative to current regenerative medicine strategies. Statement of Significance Aggrecan is a natural biomolecule that is essential for connective tissue hydration and mechanics. Aggrecan is composed of negatively charged chondroitin sulfate bristles attached to a protein core in a bottlebrush configuration. With age and degeneration, enzymatic degradation of aggrecan outpaces cellular synthesis resulting in a loss of this important molecule. We demonstrate a novel biomimetic molecule composed of natural chondroitin sulfate bristles grafted onto an enzymatically-resistant synthetic core. Our molecule mimics a 3D architecture and charge density of the natural aggrecan, can be delivered via a simple injection and is retained in tissue after equilibrium conditioning and loading. This novel material can serve as a platform for molecular repair, drug delivery and tissue engineering in regenerative medicine approaches.

Uniaxial tension was applied to selectively digested single lamellar human cadaveric annulus fibrosus specimens to investigate the role of different biomolecules in annular biomechanics. Single layered and inter-lamellar annulus fibrosus samples were obtained from 10 isolated cadaveric lumbar intervertebral discs in one of four orientations: longitudinal, transverse, radial, and circumferential. Within each orientation the samples were subjected to a selective enzymatic digestion protocol with collagenase, elastase, chondroitinase ABC, or 1× Phosphate Buffered Saline. Uniaxial tensile tests were performed to failure at a strain rate of 0.005 s −1 . Failure stress and strain, and elastic moduli were compared among the digested conditions. The collagenase- and elastase-treated groups had the most significant effect on the mechanical properties among the orientation groups, decreasing the failure stress for both interlaminar and intralaminar groups. Collagenase-treated groups showed an increase in the failure strain following enzymatic digestion for the intralaminar groups and one interlaminar testing direction (circumferential). The chondroitinase ABC-treated group only had a significant impact on the single layer orientations, decreasing the failure stress and strain (intralaminar group). The digested properties described provide insights into the laminar mechanical behavior and the role of the molecular components to the annular mechanical behavior. Understanding annular mechanics may prove insightful in diagnosis, prevention and repair of debilitating intervertebral disc disorders and manufacturing of tissue-engineered annulus.

Intervertebral disc mechanics are affected by both disc shape and disc degeneration, which in turn each affect the other; disc mechanics additionally have a role in the etiology of disc degeneration. Finite element analysis (FEA) is a favored tool to investigate these relationships, but limited data for intervertebral disc 3D shape has forced the use of simplified or single-subject geometries, with the effect of inter-individual shape variation investigated only in specialized studies. Similarly, most data on disc shape variation with degeneration is based on 2D mid-sagittal images, which incompletely define 3D shape changes. Therefore, the objective of this study was to quantify inter-individual disc shape variation in 3D, classify this variation into independently-occurring modes using a statistical shape model, and identify correlations between disc shape and degeneration. Three-dimensional disc shapes were obtained from MRI of 13 human male cadaver L3L4 discs. An average disc shape and four major modes of shape variation (representing 90% of the variance) were identified. The first mode represented disc axial area and was significantly correlated to degeneration (R(2)=0.44), indicating larger axial area in degenerate discs. Disc height variation occurred in three distinct modes, each also involving non-height variation. The statistical shape model provides an average L3L4 disc shape for FEA that is fully defined in 3D, and makes it convenient to generate a set of shapes with which to represent aggregate inter-individual variation. Degeneration grade-specific shapes can also be generated. To facilitate application, the model is included in this paper׳s supplemental content.

Summary 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, microcomputed 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 (ROM) 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.

Chondroitin sulfate (CS) based bottle brush proteoglycan mimetics may be employed to restore tissue functionality. Synthesis of CS bottle brush structures requires immobilization of CS at its terminal end. In this study, we investigated commercially available natural CS for use in CS bottle brush synthesis. A terminal primary amine on CS was identified and utilized to conjugate amine-reactive vinyl monomers ( i.e. acrylic acid and allyl glycidyl ether). Conjugation of vinyl monomers to the CS terminal amine was confirmed using a fluorescamine assay, 1 H NMR, and ATR-FTIR. CS was also immobilized onto epoxy functionalized surfaces via the CS terminal primary amine as confirmed by contact angle measurements of surface wettability. Attachment of polymeriziable end groups to CS and attachment of CS to functionalized substrates demonstrated here are the first steps towards synthesis of CS bottle brush PG mimics.

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.

This review challenges an earlier view that the intervertebral joint could not be classified as a diarthrodial joint and should remain as an amphiarthrosis. However, a careful analysis of the relevant literature and in light of more recent studies, it is clear that while some differences exist between the spinal articulation and the generic synovial joint, there are clear structural, functional and developmental similarities between the joints that in sum outweigh the differences. Further, since the intervertebral motion segment displays movement in three dimensions and the whole spine itself provides integrated rotatory movements, it is proposed that it should be classified not as an amphiarthrose, "a slightly moveable joint" but as a complex polyaxial joint. Hopefully, reclassification will encourage further analysis of the structure and function of the two types of overlapping joints and provide common new insights into diseases that afflict the many joints of the human skeleton.

A significant biochemical change that takes place in intervertebral disc degeneration is the loss of proteoglycans in the nucleus pulposus. Proteoglycans attract fluid, which works to reduce mechanical stresses in the solid matrix of the nucleus and provide a hydrostatic pressure to the annulus fibrosus, whose fibrous nature accommodates this stress. Our goals are to develop an osmo-poroelastic finite element model to study the relationship between proteoglycan content and the stress distribution within the disc and to analyze the effects of degeneration on the disc's diurnal mechanical response. Stress in the annulus increased with degeneration from ∼0.2 to 0.4 MPa, and an increase occurred in the center of the nucleus from 1.2 to 1.6 MPa. The osmotic pressure in the central nucleus region decreased the most with degeneration, from ∼0.42 to ∼0.1 MPa in a severely dehydrated disc. A 3% decrease in diurnal fluid lost with degeneration equated to ∼21% decrease in fluid exchange, and hence a decrease in nutrients that require convection to enter the disc. We quantified the increases in internal stresses in the nucleus and annulus throughout the various stages of degeneration, suggesting that these changes lead to further remodeling of the tissue. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:122–128, 2012

The intervertebral disc maintains a balance between externally applied loads and internal osmotic pressure. Fluid flow plays a key role in this process, causing fluctuations in disc hydration and height. The objectives of this study were to quantify and model the axial creep and recovery responses of nondegenerate and degenerate human lumbar discs. Two experiments were performed. First, a slow compressive ramp was applied to 2000 N, unloaded to allow recovery for up to 24 hours, and re-applied. The linear-region stiffness and disc height were within 5% of the initial condition for recovery times greater than 8 hours. In the second experiment, a 1000 N creep load was applied for four hours, unloaded recovery monitored for 24 hours, and the creep load repeated. A viscoelastic model comprised of a “fast” and “slow” exponential response was used to describe the creep and recovery, where the fast response is associated with flow in the nucleus pulposus (NP) and endplate, while the slow response is associated with the annulus fibrosus (AF). The study demonstrated that recovery is 3-4X slower than loading. The fast response was correlated with degeneration, suggesting larger changes in the NP with degeneration compared to the AF. However, the fast response comprised only 10-15% of the total equilibrium displacement, with the AF-dominated slow response comprising 40-70%. Finally, the physiological loads and deformations and their associated long equilibrium times confirm that diurnal loading does not represent “equilibrium” in the disc, but that over time the disc is in steady-state.

Study Design. Biomechanics of human intervertebral discs before and after nucleotomy. Objective. To noninvasively quantify the effect of nucleotomy on internal strains under axial compression inexion, neutral, and extension positions, and to determine whether the change in strains depended on degeneration. Summary of Background Data. Herniation and nucleotomy may accelerate the progression of disc degeneration. Removal of nucleus pulposus (NP) tissue has resulted in altered disc mechanics in vitro , including a decrease in internal pressure and an increase in the deformations at physiologically relevant strains. We recently presented a technique to quantify internal disc strains using magnetic resonance imaging (MRI). Methods. Degeneration was quantitatively assessed by the T 1 ρ relaxation time in the NP. Samples were prepared from human levels L3-L4 and/or L4-L5. A 1000-N compressive load was applied while in the magnetic resonance scanner. Nucleotomy was performed by removing 2 g of NP through the posterior-lateral annulusbrosus (AF). The discs were rehydrated, reimaged, and retested. The analyzed parameters include axial deformation, AF radial bulge, and strains. Results. The axial deformation was more compressive after nucleotomy. In the neutral position, the axial deformation after nucleotomy correlated with degeneration (as quantied by T 1 ρ in the NP), with minimal alteration in nondegenerated discs. Nucleotomy altered the radial displacements and strains in the neutral position, such that the inner AF radial bulge decreased and the radial strains were more tensile in the lateral AF and less tensile in the posterior AF. In the bending loading positions the radial strains were not affected by nucleotomy. Conclusion. Nucleotomy alters the internal radial and axial AF strains in the neutral position, which may leave the AF vulnerable to damage and microfractures. In bending, the effects of nucleotomy were minimal, likely due to more of the applied load being directed over the AF. Some of the nucleotomy effects are modulated by degeneration, where the mechanical effect of nucleotomy was magnied in degenerated discs and may further induce mechanical

Axial loading, rotation, and bending were applied to human cadaveric lumbar segments to investigate the changes in disc mechanics with denucleation and incremental delivery of a novel hydrogel nucleus replacement.The purpose of this study was to investigate the effect of nucleus implant injection pressure/volume relationships on the quasi-static mechanical behavior of the human cadaveric lumbar intervertebral disc to determine if intact biomechanics could be reproduced with nucleus-implanted discs.Previous studies have shown that volumetric filling of the nucleus cavity with a compliant nucleus replacement device will affect compressive stiffness of the implanted intervertebral disc, but data regarding restoration of mechanics through cavity pressurization are lacking.A total of 12 intact lumbar anterior column units were loaded in series in axial loading, axial rotation, lateral bending, and flexion/extension (FE). Each segment was fully denucleated and implanted with a hydrogel nucleus replacement using pressurization between 12 psi and 40 psi. Range of motion (ROM), neutral zone (NZ), energy dissipation (HYS), disc height (DH), and stiffness were compared among the intact, denucleated, and implanted conditions.Denucleation significantly destabilized the segments compared to intact controls as shown by increased ROM, NZ, and HYS, and decreased DH and stiffness through the NZ. As the nucleus cavity was repressurized with increasing volumes of hydrogel implant, the segments were stabilized and DH was restored to the intact level. No significant differences from intact were observed in any loading direction for ROM, NZ, or DH after the segments were implanted with the nucleus replacement device using inflation pressures between 20 psi and 40 psi.Compliant nucleus replacement using inflation pressures of 20 to 40 psi resulted in restoration of intact mechanics. Mechanical function was dependent on the volume of implant injected into the nucleus cavity.

A simplified finite element model of the human lumbar intervertebral disc was utilized for understanding nucleus pulposus implant mechanics. The model was used to assess the effect of nucleus implant parameter variations on the resulting compressive biomechanics of the lumbar anterior column unit. The effects of nucleus implant material (modulus and Poisson's ratio) and geometrical (height and diameter) parameters on the mechanical behavior of the disc were investigated. The model predicted that variations in implant modulus contribute less to the compressive disc mechanics compared to the implant geometrical parameters, for the ranges examined. It was concluded that some threshold exists for the nucleus implant modulus, below which little variations in load-displacement behavior were shown. Compressive biomechanics were highly affected by implant volume (under-filling the nucleus cavity, line-to-line fit, or over-filling the nucleus cavity) with a greater restoration of compressive mechanics observed with the over-filled implant design. This work indicated the effect of nucleus implant parameter variations on the compressive mechanics of the human lumbar intervertebral disc and importance of the "fit and fill" effect of the nuclear cavity in the restoration of the human intervertebral disc mechanics in compression. These findings may have clinical significance for nucleus implant design.

Object The objective of this systematic review was to use evidence-based medicine to delineate the natural history of cervical spondylotic myelopathy (CSM) and identify factors associated with clinical deterioration. Methods The National Library of Medicine and Cochrane Database were queried using MeSH headings and keywords relevant to the natural history of CSM. Abstracts were reviewed and studies meeting the inclusion criteria were selected. The guidelines group assembled an evidentiary table summarizing the quality of evidence (Classes I–III). Disagreements regarding the level of evidence were resolved through an expert consensus conference. The group formulated recommendations that contained the degree of strength based on the Scottish Intercollegiate Guidelines network. Validation was done through peer review by the Joint Guidelines Committee of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons. Results The natural history of CSM is mixed: it may manifest as a slow, stepwise decline or there may be a long period of quiescence (Class III). Long periods of severe stenosis are associated with demyelination and may result in necrosis of both gray and white matter. With severe and/or long lasting CSM symptoms, the likelihood of improvement with nonoperative measures is low. Objectively measurable deterioration is rarely seen acutely in patients younger than 75 years of age with mild CSM (modified Japanese Orthopaedic Association scale score > 12; Class I). In patients with cervical stenosis without myelopathy, the presence of abnormal electromyography findings or the presence of clinical radiculopathy is associated with the development of symptomatic CSM in this patient population (Class I). Conclusions The natural history of CSM is variable, which may affect treatment decisions.

Object The objective of this systematic review was to use evidence-based medicine to assess whether preoperative imaging or electromyography (EMG) predicts surgical outcomes in patients undergoing cervical surgery. Methods The National Library of Medicine and Cochrane Database were queried using MeSH headings and keywords relevant to the preoperative imaging and EMG. Abstracts were reviewed after which studies meeting inclusion criteria were selected. The guidelines group assembled an evidentiary table summarizing the quality of evidence (Classes I–III). Disagreements regarding the level of evidence were resolved through an expert consensus conference. The group formulated recommendations that contained the degree of strength based on the Scottish Intercollegiate Guidelines network. Validation was done through peer review by the Joint Guidelines Committee of the American Association of Neurological Surgeons/Congress of Neurological Surgeons. Results Preoperative MR imaging and CT myelography are successful in confirming clinical radiculopathy (Class II). Multilevel T2 hyperintensity, T1 focal hypointensity combined with T2 focal hyperintensity, and spinal cord atrophy each convey a poor prognosis (Class III). There is conflicting data concerning whether focal T2 hyperintensity or cervical stenosis are associated with a worse outcome. Electromyography has mixed utility in predicting outcome (Class III). Conclusions Magnetic resonance imaging or CT myelography are important for preoperative assessment. Magnetic resonance imaging may be helpful in assessing prognosis, whereas EMG has mixed utility in assessing outcome.

Object The objective of this systematic review was to use evidence-based medicine to identify the indications and utility of anterior cervical nerve root decompression. Methods The National Library of Medicine and Cochrane Database were queried using MeSH headings and key words relevant to surgical management of cervical radiculopathy. Abstracts were reviewed after which studies meeting inclusion criteria were selected. The guidelines group assembled an evidentiary table summarizing the quality of evidence (Classes I–III). Disagreements regarding the level of evidence were resolved through an expert consensus conference. The group formulated recommendations that contained the degree of strength based on the Scottish Intercollegiate Guidelines network. Validation was done through peer review by the Joint Guidelines Committee of the American Association of Neurological Surgeons/Congress of Neurological Surgeons. Results Anterior nerve root decompression via anterior cervical discectomy (ACD) with or without fusion for radiculopathy is associated with rapid relief (3–4 months) of arm/neck pain, weakness, and/or sensory loss compared with physical therapy (PT) or cervical collar immobilization. Anterior cervical discectomy and ACD with fusion (ACDF) are associated with longer term (12 months) improvement in certain motor functions compared to PT. Other rapid gains observed after anterior decompression (diminished pain, improved sensation, and improved strength in certain muscle groups) are also maintained over the course of 12 months. However, comparable clinical improvements with PT or cervical immobilization therapy are also present in these clinical modalities (Class I). Conflicting evidence exists as to the efficacy of anterior cervical foraminotomy with reported success rates of 52–99% but recurrent symptoms as high as 30% (Class III). Conclusions Anterior cervical discectomy, ACDF, and anterior cervical foraminotomy may improve cervical radicular symptoms. With regard to ACD and ACDF compared to PT or cervical immobilization, more rapid relief (within 3–4 months) may be seen with ACD or ACDF with maintenance of gains over the course of 12 months (Class I). Anterior cervical foraminotomy is associated with improvement in clinical function but the quality of data are weaker (Class III), and there is a wide range of efficacy (52–99%).

Object The objective of this systematic review was to use evidence-based medicine to examine the efficacy of posterior laminoforaminotomy in the treatment of cervical radiculopathy. Methods The National Library of Medicine and Cochrane Database were queried using MeSH headings and key words relevant to posterior laminoforaminotomy and cervical radiculopathy. Abstracts were reviewed, and studies meeting inclusion criteria were selected. The guidelines group assembled an evidentiary table summarizing the quality of evidence (Classes I–III). Disagreements regarding the level of evidence were resolved through an expert consensus conference. The group formulated recommendations which contained the degree of strength based on the Scottish Intercollegiate Guidelines network. Validation was done through peer review by the Joint Guidelines Committee of the American Association of Neurological Surgeons/Congress of Neurological Surgeons. Results Posterior laminoforaminotomy improves clinical outcome in the treatment of cervical radiculopathy resulting from soft lateral cervical disc displacement or cervical spondylosis with resulting narrowing of the lateral recess. All studies were Class III. The most frequent design flaw involved the lack of utilization of validated outcomes measures. In addition, few historical studies included a detailed preoperative analysis of the patients. As such, the vast majority of studies that included both pre- and postoperative assessments with legitimate outcomes measures have been performed since 1990. Conclusions Posterior laminoforaminotomy is an effective treatment for cervical radiculopathy.

Object The objective of this systematic review was to use evidence-based medicine to examine the efficacy of cervical laminectomy and fusion for the treatment of cervical spondylotic myelopathy (CSM). Methods The National Library of Medicine and Cochrane Database were queried using MeSH headings and keywords relevant to cervical laminectomy, fusion, and CSM. Abstracts were reviewed, after which studies that met the inclusion criteria were selected. The guidelines group assembled an evidentiary table summarizing the quality of evidence (Class I–III). Disagreements regarding the level of evidence were resolved through an expert consensus conference. The group formulated recommendations which contained the degree of strength based on the Scottish Intercollegiate Guidelines network. Validation was done through peer-review by the Joint Guidelines Committee of the American Association of Neurological Surgeons/Congress of Neurological Surgeons. Results Cervical laminectomy with fusion (arthrodesis) improves functional outcome in patients with CSM and ossification of the posterior longitudinal ligament (OPLL). Functional improvement is similar to laminectomy or laminoplasty for patients with CSM and OPLL. In contrast to laminectomy, cervical laminectomy with fusion it is not associated with late deformity (Class III). Conclusions Laminectomy with fusion (arthrodesis) is an effective strategy to improve functional outcome in CSM and OPLL.

Object The objective of this systematic review was to use evidence-based medicine to determine the efficacy of interbody graft techniques. Methods The National Library of Medicine and Cochrane Database were queried using MeSH headings and keywords relevant to cervical interbody grafting. Abstracts were reviewed and studies that met the inclusion criteria were selected. The guidelines group assembled an evidentiary table summarizing the quality of evidence (Classes I–III). Disagreements regarding the level of evidence were resolved through an expert consensus conference. The group formulated recommendations that contained the degree of strength based on the Scottish Intercollegiate Guidelines network. Validation was done through peer review by the Joint Guidelines Committee of the American Association of Neurological Surgerons/Congress of Neurological Surgeons. Results Autograft bone harvested from the iliac crest, allograft bone from either cadaveric iliac crest or fibula, or titanium cages and rectangular fusion devices, with or without the use of autologous graft or substitute, have been successful in creating arthrodesis after 1- or 2-level anterior cervical discectomy with fusion (Class II). Alternatives to autograft, allograft, or titanium cages include polyetheretherketone cages and carbon fiber cages (Class III). Polyetheretherketone cages have been used successfully with or without hydroxyapatite for anterior cervical discectomy with fusion. Importantly, recombinant human bone morphogenic protein-2 carries a complication rate of up to 23–27% (especially local edema) compared with 3% for a standard approach. Conclusions Current evidence does not support the routine use of interbody grafting for cervical arthrodesis. Multiple strategies for interbody grafting have been successful with Class II evidence supporting the use of autograft, allograft, and titanium cages.

Background: Early diagnosis is a challenge in the treatment of degenerative disc disease. A noninvasive biomarker detecting functional mechanics of the disc is needed. T1ρ-weighted imaging, a spin-lock magnetic resonance imaging technique, has shown promise for meeting this need in in vivo studies demonstrating the clinical feasibility of evaluating both intervertebral discs and articular cartilage. The objectives of the present study were (1) to quantitatively determine the relationship between T1ρ relaxation time and measures of nucleus pulposus mechanics, and (2) to evaluate whether the quantitative relationship of T1ρ relaxation time with the degenerative grade and glycosaminoglycan content extend to more severe degeneration. It was hypothesized that the isometric swelling pressure and compressive modulus would be directly correlated with the T1ρ relaxation time and the apparent permeability would be inversely correlated with the T1ρ relaxation time. Methods: Eight cadaver human lumbar spines were imaged to measure T1ρ relaxation times. The nucleus pulposus tissue from the L1 disc through the S1 disc was tested in confined compression to determine the swelling pressure, compressive modulus, and permeability. The glycosaminoglycan and water contents were measured in adjacent tissue. Linear regression analyses were performed to examine the correlation between the T1ρ relaxation time and the other measured variables. Mechanical properties and biochemical content were evaluated for differences associated with degeneration. Results: A positive linear correlation was observed between the T1ρ relaxation time on the images of the nucleus pulposus and the swelling pressure (r = 0.59), glycosaminoglycan content per dry weight (r = 0.69), glycosaminoglycan per wet weight (r = 0.49), and water content (r = 0.53). No significant correlations were observed between the T1ρ relaxation time and the modulus or permeability. Similarly, the T1ρ relaxation time, swelling pressure, glycosaminoglycan content per dry weight, and water content were significantly altered with degeneration, whereas the modulus and permeability were not. Conclusions: T1ρ-weighted magnetic resonance imaging has a strong potential as a quantitative biomarker of the mechanical function of the nucleus pulposus and of disc degeneration. Clinical Relevance: Several in vivo studies have previously demonstrated the clinical feasibility of using T1ρ-weighted imaging to evaluate both intervertebral discs and articular cartilage. Its application for the diagnosis of disc degeneration looks promising.

Study design Experimental measurement and normalization of in vitro disc axial compression mechanics and glycosaminoglycan and water content for several animal species used in intervertebral disc research. Objective To compare normalized axial mechanical properties and glycosaminoglycan and water content from other species to those of the human disc to aid in selection and interpretation of results in animal disc studies. Summary of background data There is a lack of mechanical and biochemical comparative data from animal intervertebral discs with respect to the human disc. Methods Intervertebral disc axial mechanical properties, glycosaminoglycan, and water content were evaluated for 9 disc types in 7 mammalian species: the calf, pig, baboon, sheep, rabbit, rat and mouse lumbar, and the cow and rat tail. Disc area and height were used for calculation of the normalized mechanical parameters. Glycosaminoglycan content was normalized by dry weight. Results Many directly measured mechanical parameters varied by orders of magnitude. However, these parameters became comparable and often did not show significant differences after geometric normalization. Both glycosaminoglycan and water content revealed similarity across species. Conclusion Disc axial mechanics are very similar across animal species when normalizing by the geometric parameters of disc height and area. This suggests that the disc tissue material properties are largely conserved across animal species. These results provide a reference to compare disc axial mechanics and glycosaminoglycan and water composition of experimental animal models to the human lumbar disc, to aid in both selection and interpretation of experimental disc research.

Study Design. Biomechanical study and literature review. Objectives. To quantify the acute effect of needle diameter on the in vitro mechanical properties of cadaver lumbar discs in the rat and sheep. To review published in vivo animal studies and evaluate disc changes with respect to the relative needle size. Summary of Background Data. There are many cases where a disc needle puncture or injection is applied to animal models: puncture injuries to induce degeneration, chemonucleolysis to induce degeneration, and delivery of disc therapies. It is not clear what role the size of the needle may have in the outcome. Methods. Mechanics were measured after sham phosphate buffered saline injection with a 27 G or 33 G needle in the rat and with a 27 G needle in the sheep. A literature review was performed to evaluate studies in which animal discs were treated with a needle puncture or a sham injection. For each study, the ratio of the needle diameter to disc height (needle:height) was calculated. Results. When the rat was injected with a 27 G needle (52% of disc height), the compression, tension, and neutral zone stiffnesses were 20% to 60% below preinjected values and the neutral zone length was 130% higher; when injected with a 33 G needle (26% of disc height), the only affected property was the neutral zone length, which was only 20% greater. When the sheep was injected with a 27 G needle (10% of disc height), none of the axial properties were different from intact, the torsion stiffness was not different, and the torque range was 15% smaller. Twenty-three in vivo studies in the rat, rabbit, dog, or sheep were reviewed. The disc changes depended on the ratio of needle diameter to disc height as follows: significant changes were not observed for needle:height less than 40%, although between 25% and 40% results were variable and some minor nonsignificant effects were observed, disc changes were universal for needle:height over 40%. Conclusion. A needle puncture may directly alter mechanical properties via nucleus pulposus depressurization and/or anulus fibrosus damage, depending on the relative needle size. As more basic science research is aimed at treating disc degeneration via injection of therapeutic factors, these findings provide guidance in design of animal studies. Such studies should consider the relative needle size and include sham control groups to account for the potential effects of the needle injection.

Geometry is an important indicator of disc mechanical function and degeneration. While the geometry and associated degenerative changes in the nucleus pulposus and the annulus fibrosus are well-defined, the geometry of the cartilage endplate (CEP) and its relationship to disc degeneration are unknown. The objectives of this study were to quantify CEP geometry in three dimensions using an MRI FLASH imaging sequence and evaluate relationships between CEP geometry and age, degeneration, spinal level, and overall disc geometry. To do so, we assessed the MRI-based measurements for accuracy and repeatability. Next, we measured CEP geometry across a larger sample set and correlated CEP geometric parameters to age, disc degeneration, level, and disc geometry. The MRI-based measures resulted in thicknesses (0.3-1 mm) that are comparable to prior measurements of CEP thickness. CEP thickness was greatest at the anterior/posterior (A/P) margins and smallest in the center. The CEP A/P thickness, axial area, and lateral width decreased with age but were not related to disc degeneration. Age-related, but not degeneration-related, changes in geometry suggest that the CEP may not follow the progression of disc degeneration. Ultimately, if the CEP undergoes significant geometric changes with aging and if these can be related to low back pain, a clinically feasible translation of the FLASH MRI-based measurement of CEP geometry presented in this study may prove a useful diagnostic tool. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1410-1417, 2016.

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.

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. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1264-1273, 2016.

Emerging techniques as an alternative to the current treatments of lower back pain include nucleus replacement by an artificial material, which aims to relieve pain and restore the normal spinal motion. The compressive mechanical behavior of the PVA/PVP hydrogel nucleus implant was assessed in the present study. PVA/PVP hydrogels were made with various PVP concentrations. The hydrogels were loaded statically under unconfined and confined conditions. Hydrogels were tested dynamically up to 10 million cycles for a compression fatigue. Also, hydrogel nucleus implants with a line-to-line fit, were implanted in the human cadaveric intervertebral discs (IVD) to determine the compressional behavior of the implanted discs. Hydrogel samples exhibited typical non-linear response under both unconfined and confined compressions. Properties of the confinement ring dictated the observed response. Hydrogel moduli and polymer content were not different pre- and post-fatigues. Slight geometrical changes (mostly recoverable) were observed post-fatigue. In cadavers, hydrogels restored the compressive stiffness of the denucleated disc when compared with equivalent condition of the IVD. The results of this study demonstrate that PVA/PVP hydrogels may be viable as nucleus pulposus implants. Further studies under complex loading conditions are warranted to better assess its potential as a replacement to the degenerated nucleus pulposus.

Traumatic spondylopelvic dissociation is an extremely rare injury resulting in mechanical dissociation of the pelvis from the spine1. Similar mechanical dysfunction can occur in association with lumbosacral fracture-dislocation or bilateral sacroiliac joint dislocation2-9. However, traumatic spondylopelvic dissociation is a distinct injury pattern, characterized by a transverse sacral fracture in conjunction with bilateral sacroiliac fracture-dislocation, that requires a unique approach to overall patient management and surgical stabilization1,10-12. Options for the surgical treatment of spondylopelvic dissociation are limited as the sacrum may not provide structural support or stability for internal fixation. Our patients were informed that data concerning the cases would be submitted for publication. Case 1. A nineteen-year-old woman who was wearing a helmet while riding as a passenger on a motorcycle was ejected at high speed, struck a tree, and subsequently was run over by an eighteen-wheel tractor-trailer. She initially presented to an outside hospital with a Glasgow Coma Score of 15 but was unable to move either lower extremity. She was intubated because of respiratory distress, and a chest tube was inserted bilaterally for the treatment of pneumothorax. A diagnostic peritoneal lavage was positive, and the patient underwent exploratory laparotomy. She had multiple musculoskeletal injuries, including spondylopelvic dissociation with highly comminuted sacral fractures that had both vertical and transverse components (Fig. 1-A), a closed fracture of the proximal part of the right femoral shaft, a comminuted fracture of the left acetabulum, open midshaft fractures of the left tibia and fibula, left metacarpal fractures, and degloving injuries of both feet. The open fractures of the left tibia and fibula were irrigated and debrided in the operating room and then were stabilized with external fixation. A traction pin was placed in the distal part of each femur. The …

Nucleus replacement by a synthetic material is a recent trend for treatment of lower back pain. Hydrogel nucleus implants were prepared with variations in implant modulus, height, and diameter. Human lumbar intervertebral discs (IVDs) were tested in compression for intact, denucleated, and implanted condition. Implantation of nucleus implants with different material and geometric parameters into a denucleated IVD significantly altered the IVD compressive stiffness. Variations in the nucleus implant parameters significantly change the compressive stiffness of the human lumbar IVD. Implant geometrical variations were more effective than those of implant modulus variations in the range examined.

Spinal injuries occur frequently in the patient with polytrauma making the knowledge of the evaluation and treatment of these injuries invaluable to the trauma team. In the immediate moments after these injuries, critical steps can be taken to prevent additional injury and insure maximum neurologic and functional recovery of the patient. A simple, standardized approach to treating the patient at the scene, examining the patient in the trauma admitting area, ordering appropriate radiographic studies, and instituting early treatment can markedly influence a patient's maximal recovery. Furthermore, background knowledge in the classification and ultimate treatment goals allows for an effective communication between the initial treating team and the spinal surgeons involved. The work on indicators of potential spinal instability by White and Panjabi and the three-column classification of spinal injuries of Denis lends insight to the potential consequences of spinal trauma. A thorough appreciation of these concepts puts evaluation and treatment of these injuries into a logical framework with which spinal injuries initially can be approached.

STUDY DESIGN The goal of this study was to develop a methodology to maintain intervertebral discs in organ culture, thereby preserving tissue architecture and metabolic function in a three-dimensional environment. METHODS Using a microdissection technique, intervertebral discs were removed from rat lumbar vertebrae. The discs were maintained in organ culture, and cell viability was evaluated histochemically and using probes that measured mitochondrial function and thiol status. The biosynthetic activity of the cells was evaluated by Western blot and RT-PCR analysis. RESULTS The in vitro organ culture system maintained the vitality of the nucleus pulposus cells. Cells exhibited a high membrane potential for 1 week. When cells were exposed to carbonyl cyanide 4-trifluoromethoxy phenylhydrazone, a known protonophore, the fluorescence was lost, indicating that the staining was specific for viable cells. In many cells, Celltracker Green, probe for reduced thiols, colocalized with the membrane potential. Histologic studies revealed that in culture for 1 week, normal nucleus pulposus structure was maintained; after this time period, alterations were observed. We evaluated the two tissues for characteristic phenotypic markers HIF-1alpha and MMP-2. We noted that the nucleus pulposus expressed these proteins. The RT-PCR profile at 7 days indicated that the cells also expressed collagen type II, aggrecan, and decorin. DISCUSSION Three factors contributed to success in maintaining the vitality of the nucleus pulposus in vitro. First, the cells were confined within the disc itself; second, the medium was hyperosmotic; third, the medium was supplemented with transforming growth factor-beta. The fluorescence measurement provided a rapid method for evaluation of the status of nucleus pulposus cells. Histologic analysis confirmed that the cells remained viable for at least 1 week. Viability in terms of biosynthetic activity was further confirmed using RT-PCR and Western blot analysis. We conclude that short-term intervertebral disc organ culture can be used as a suitable in vitro model to study effects of environmental factors linked to disc degeneration and/or regeneration.

It is universally accepted that an anatomic abnormality such as a herniated disc or spinal stenosis can lead to radicular leg pain. There is some controversy as to whether radicular pain can be caused by a non-structural, solely biochemical disorder. Prior studies using biochemical analysis of inflammatory mediators of the disc or surrounding structures have enumerated many possible biochemical mediators of radicular pain. However, such studies have not definitively demonstrated whether these inflammatory mediators are the causes of radicular pain or whether these mediators are simply products of the degenerative cascade. The purpose of this paper is to report upon patients who satisfy strict criteria affirming a diagnosis of radiculopathy in the presence of normal imaging studies. The study was designed as a prospective case series of patients fulfilling inclusion and exclusion criteria at a university hospital outpatient physiatric spine practice. Inclusion criteria consisted of symptoms of extremity pain greater than axial pain, examination findings demonstrating a new myotomal deficit that correlates with the root level predicted by the dermatomal pain distribution, and failure to improve after at least 4 weeks of active physical therapy. Magnetic resonance imaging void of local nerve root pathology as per review by the first author and the interpreting radiologist was required. Each patient had to have a positive electromyographic study for an acute radiculopathy. Each patient had to have a positive fluoroscopically guided diagnostic selective nerve root block. In summary, this paper provides clinical evidence that anatomic abnormalities are not required to cause radiculopathy, thus implying that a biochemical etiology is likely to play a significant role in radiculopathy and radicular pain.

Attempts to study the biology of the nucleus pulposus have been limited in scope due to the low rates of cell proliferation, difficulties in maintaining viable disc cells in culture and the absence of a clearly defined phenotype. The major objective of this communication is to construct a phenotypic signature for cells of the nucleus pulposus that is based on the hypothesis that in response to restriction on oxygen and nutrient flux, there is expression of HIF-1, GLUT-1 and MMP-2. Nucleus pulposus, as well as annulus fibrosus and cartilage of the vertebral end plates, was collected from rat spinal units. Western blot analysis and immunohistochemistry clearly showed that there was a significant level of expression of the HIF-1 beta isoform in the nucleus pulposus; HIF-1 beta was present at lower levels in cells of the annulus and the end plate. In contrast to HIF-1 beta, HIF-1 alpha was expressed only in the nucleus pulposus. This isoform was absent from both the cartilage end plate and annulus. We detected HIF-1 alpha immunohistochemically in the nucleus pulposus; however, the staining was light and diffuse. Cells of the nucleus pulposus expressed GLUT-1; in contrast, when probed by Western blot analysis the annulus and cartilage were negative for this protein. Western blot analysis also showed that in the nucleus pulposus the level of MMP-2 was high when compared to the adjacent tissues. We suggest that the differential expression of the two HIF isoforms, and GLUT-1 and MMP-2, provides a phenotypic signature that permits cells of the nucleus pulposus to be distinguished from neighboring tissues. Moreover, the presence of these isoforms provides evidence that cells of the disc respond to hypoxia and nutrient stress by upregulating stress-responsive genes.

The intervertebral disc functions to permit motion, distribute load, and dissipate energy in the spine. It performs these functions through its highly heterogeneous structural organization and biochemical composition consisting of several tissue substructures: the central gelatinous nucleus pulposus (NP), the surrounding fiber-reinforced layered AF, and the cartilaginous endplates that are positioned between the NP and vertebral endplates [1]. Disruption of any of the disc's tissues through aging, degeneration, or injury will not only alter the affected tissue mechanical properties but also the mechanical behavior of adjacent tissues and, ultimately, the overall disc segment function. Thus, there is a need to measure disc tissue and segment mechanics in the intact disc segment so that interactions between tissue structures are not disrupted. Such measurements would be valuable to study mechanisms of disc function and of disc degeneration, to design functional tissue engineered discs, and to develop and evaluate surgical procedures and therapeutic implants. Disc mechanical behavior has been quantified through a number of measures including external displacements [2–5] and internal pressure [6–9]; however, these do not fully establish internal tissue mechanics. Internal disc mechanics have also been measured through marker insertion or disc bisection [10–14]. These studies have provided important data about disc mechanical function and how it changes with degeneration. Yet the disc is composed of soft hydrated, pressurized, and fibrous tissues that may deform separately from the inserted markers and may depressurize when bisected. Thus, it has remained a challenge to quantify internal disc mechanics. Magnetic resonance imaging (MRI) before and after an applied load, combined with image registration, is a promising method to quantify internal disc mechanics. Important advances have been made using MRI to measure internal disc deformation in a 2D plane [15–19]. Strains within several AF regions (e.g., anterior, posterior, and lateral) were measured under applied axial compression, and the effect of loading position, degeneration, and nucleotomy was determined [16–18], demonstrating inhomogeneous strains across AF regions and differential effects of nucleotomy that depend on the initial state of degeneration [16–18]. A nonrigid image registration method was employed by [19] to calculate midsagittal strain after creep loading. Displacement encoded MRI, an image tagging method that enables direct displacement measurements from MRI data, was used in Ref. [15] to calculate strain across the entire disc under cyclic loading. While these are important advances, the 2D nature of recent MRI-based studies do not account for out-of-plane deformation nor provide the 3D strain components that are key to evaluating disc mechanical function. The objectives of this study were to develop, validate, and apply a method to measure 3D internal deformations in intact human discs subjected to axial compression. This was achieved by using a custom-built loading device that permitted long relaxation times outside of the MRI scanner and maintained compression and hydration during imaging, by acquiring MR images at a high resolution (300 μm isotropic), and by applying state-of-the-art image registration methods.

Back injury is one of the most frequently encountered injuries in the collegiate rower. The differential diagnosis of back pain in the competitive rower includes muscle strain, ligament/tendon injury, stress reaction, stress fracture, and a tear in the annulus fibrosis. Endurance sports, such as rowing, have an increased frequency of stress injury The diagnosis of stress reaction cannot be made with plain radiographs. Many studies have firmly established the efficacy of single photon emission computed tomography (SPECT) bone scans and magnetic resonance imaging in establishing the diagnosis of a stress reaction We present a case of a collegiate rower with mid back pain secondary to a stress reaction of the endplates of the costotransverse articulation at the T8 level diagnosed by a positive positron emission tomogram study in the setting of a negative SPECT scan.

To investigate the outcomes resulting from the use of fluoroscopically guided therapeutic sacroiliac joint injections in patients with sacroiliac joint syndrome.A retrospective study design with independent clinical review was utilized. Thirty-one patients were included; each patient met specific physical examination criteria and failed to improve clinically after at least 4 wk of physical therapy. Each patient demonstrated a positive response to a fluoroscopically guided diagnostic sacroiliac joint injection. Therapeutic sacroiliac joint injections were administered in conjunction with physical therapy. Outcome measures included Oswestry scores, Visual Analog Scale pain scores, work status, and medication usage.Patients' symptom duration before diagnostic injection averaged 20.6 mo. An average of 2.1 therapeutic injections was administered. Follow-up data collection was obtained at an average of 94.4 wk. A significant reduction (P = 0.0014) in Oswestry disability score was observed at the time of follow-up. Visual Analog Scale pain scores were reduced (P0.0001) at the time of discharge and at follow-up. Work status was also significantly improved at the time of discharge (P = 0.0313) and at follow-up (P = 0.0010). A trend (P = 0.0645) toward less drug usage was observed.These initial findings suggest that fluoroscopically guided therapeutic sacroiliac joint injections are a clinically effective intervention in the treatment of patients with sacroiliac joint syndrome. Controlled, prospective studies are necessary to further clarify the role of therapeutic injections in this patient population.

This study was designed to investigate the clinical efficacy of fluoroscopically guided therapeutic cervical selective nerve root blocks (SNRBs) in patients with whiplash induced cervical radicular pain. Study design was restrospective with independent clinical review. Twenty two patients were included. Each patient met specific physical examination criteria and failed to improve clinically after at least four weeks of physical therapy and the use of oral analgesics. Each patient demonstrated a positive response to a fluoroscopically guided diagnostic cervical SNRB. Patients were excluded for radiographic evidence of a focal disc protrusion or foraminal stenosis at the symptomatic level. Therapeutic cervical SNRBs were administered in conjunction with physical therapy. Data collection and analysis were performed by an independent clinical reviewer. Outcome measures included VAS pain scores, work status, medication usage, and Oswestry disability scores. Results showed the patients' symptom duration prior to diagnostic injection averaged 6 months. An average of 2.1 therapeutic injections was administered. Follow up data collection transpired at an average of 33.3 weeks following the final therapeutic injection. Good or excellent results were observed in 14% of patients. In higher functioning individuals a significantly greater (F=.0427) improvement in pain of 48.9% was observed. In these initial findings suggest that fluoroscopically guided therapeutic SNRBs, except possibly for higher functioning individuals, are not effective in the treatment of whiplash induced cervical radicular pain.

A case of thoracic spine spasms secondary to a bleeding duodenal ulcer is presented. A 41-year-old male with 14-week history of thoracic spine spasm was treated with bed rest, spinal manipulation, physical therapy, medication, and a thoracolumbar brace. Subsequently, a provocative thoracic discogram performed at T9-T10 created periscapular pain and also reproduced the presenting thoracic spasms. Intradiscal electrothermal annuloplasty (IDET) was performed at the T9-T10 level, but without sustained relief. The patient presented to a spine center for evaluation. The diagnosis of thoracic discogenic disease was suspected. A second provocative thoracic discogram was performed and failed to reproduce his thoracic spasms. Three weeks after being referred to a chronic pain management physician, the patient presented to a local emergency room with hema-temesis. An endoscopic evaluation revealed a bleeding duodenal ulcer. Following medical treatment of the duodenal ulcer with a proton pump inhibitor the patient had complete resolution of his thoracic spasms. This represents the first reported case of thoracic spine spasms as an initial presenting symptom of a bleeding peptic ulcer.

Slipman CW, Lipetz JS, Jackson HB, Rogers DP, Vresilovic EJ. Therapeutic selective nerve root block in the nonsurgical treatment of atraumatic cervical spondylotic radicular pain: a retrospective analysis with independent clinical review. Arch Phys Med Rehabil 2000;81:741-6. Objective: To investigate the outcomes resulting from the use of fluoroscopically guided therapeutic selective nerve root block (SNRB) in the nonsurgical treatment of atraumatic cervical spondylotic radicular pain. Study Design: Retrospective study with independent clinical review. Participants: Twenty subjects (10 men, 10 women) with mean age 56.6 years. Methods: Each patient met specific physical examination, radiographic, and electrodiagnostic criteria to confirm a level of cervical involvement. Those patients whose root level remained indeterminate were required to demonstrate a positive response to a fluoroscopically guided diagnostic SNRB prior to the initiation of treatment. Therapeutic injections were administered in conjunction with physical therapy. Data collection and analysis were performed by an independent clinical reviewer. Main Outcome Measures: Pain score, work status, medication usage, and patient satisfaction. Results: Twenty patients with an average symptom duration of 5.8 months were included. An average of 2.2 therapeutic injections was administered. Follow-up data collection transpired at an average of 21.2 months following discharge from treatment. A significant reduction ( p =.001) in pain score was observed at the time of follow-up. Medication usage was also significantly improved ( p =.005) at the time of follow-up. An overall good or excellent result was observed in 60%. Thirty percent of patients required surgery. Younger patients were more likely ( p =.0047) to report the highest patient satisfaction rating following treatment. Conclusions: This study suggests that fluoroscopically guided therapeutic SNRB is a clinically effective intervention in the treatment of atraumatic cervical spondylotic radicular pain. © 2000 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

Slipman CW, Jackson HB, Lipetz JS, Chan KT, Lenrow D, Vresilovic EJ. Sacroiliac joint pain referral zones. Arch Phys Med Rehabil 2000;81:334-8. Objective: To determine the patterns of pain referral from the sacroiliac joint. Study Design: Retrospective. Participants/Methods: Fifty consecutive patients who satisfied clinical criteria and demonstrated a positive diagnostic response to a fluoroscopically guided sacroiliac joint injection were included. Each patient's preinjection pain description was used to determine areas of pain referral, and 18 potential pain-referral zones were established. Outcome Measures: Observed areas of pain referral. Results: Eighteen men (36.0%) and 32 women (64.0%) were included with a mean age of 42.5 years (range, 20 to 75 yrs) and a mean symptom duration of 18.2 months (range, 1 to 72 mo). Forty-seven patients (94.0%) described buttock pain, and 36 patients (72.0%) described lower lumbar pain. Groin pain was described in 7 patients (14.0%). Twenty-five patients (50.0%) described associated lower-extremity pain. Fourteen patients (28.0%) described leg pain distal to the knee, and 6 patients (14.0%) reported foot pain. Eighteen patterns of pain referral were observed. A statistically significant relationship was identified between pain location and age, with younger patients more likely to describe pain distal to the knee. Conclusions: Pain referral from the sacroiliac joint does not appear to be limited to the lumbar region and buttock. The variable patterns of pain referral observed may arise for several reasons, including the joint's complex innervation, sclerotomal pain referral, irritation of adjacent structures, and varying locations of injury with the sacroiliac joint. © 2000 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation