Chondroitinase Versus Papain Digestion Leads to Different Outcome for InVitro Simulation of Degenerated Discs.

Introduction Intradiscal therapy with condoliase is becoming one of the minimally invasive treatment options for lumbar disc herniation (LDH). However, evidence regarding its efficacy in elderly populations remains scarce. The purpose of this study is to reveal the efficacy of condoliase treatment for LDH in patients over the age of 70 years. Methods The patients with LDH who received condoliase treatment in our institution with a follow-up period of 1 year were enrolled in this study. The patients were divided into two groups according to age: group E (>70 years) and group C (20-70 years). To assess clinical outcomes, visual analog scale (VAS) scores for leg and back pain and the Oswestry Disability Index (ODI) were obtained. Disc height and degeneration were evaluated using magnetic resonance imaging. Treatment was considered effective if the VAS scores for leg pain improved by ≥50% at 1 year and surgery was avoided. Results A total of 121 patients were enrolled in the study. The therapy was effective in 12 of 17 patients (70.6%) in group E and 79 of 104 patients (76.0%) in group C. The deterioration rate of Pfirrmann grade was significantly higher in group C than in group E (53.9% vs. 7.1%). Improvements in VAS scores and ODIs were comparable between the two groups. There were no significant differences in disc height reduction or herniation reduction rates between the groups. Despite disc degeneration, herniation reduction was observed, accompanied by a decrease in disc height. Conclusions Chemonucleolysis with condoliase is effective in treating LDH in patients over 70 years of age, affording outcomes comparable to those in younger patients. Despite disc degeneration, herniation reduction was observed accompanied by a decrease in disc height. Condoliase offers a less invasive alternative for treating elderly patients with multiple comorbidities. Careful patient selection is critical for ensuring optimal clinical results.

Defining the Neutral Zone of sheep intervertebral joints during dynamic motions: an in vitro study

Introduction The rat tail model for the intervertebral disk degeneration has recently been receiving a high level of interest among the intervertebral disk degeneration studies. A better understanding of the time course and recognizing the role of mechanical manipulation may lead to development of a more reproducible model for further application in disk implanting studies. In this study, we aimed to establish a reproducible disk degeneration rat tail model by needle puncture and to assess the gradual progression of the degeneration over time. Materials and Methods Under fluoroscopic guidance, the fourth intervertebral disk space of the rat's tail in 13 mature Rowett Nude (RNU) male rats (T-Cell-Deficient, Athymic Nude Rats) was percutaneously stabbed on the left lateral side with an 18G needle. To standardize the depth of the stab, the tip of a syringe cap was cut at 5 mms point, and was then used with a new needle to puncture each new animal. The first seven rats (group 1) received no further mechanical manipulation; however in the next six rats (group 2), in addition to the needle puncture, the proximal portion of the tail including the stabbed level was then manually rotated around and compressed along to the longitudinal axis. Radiographic follow-up was carried out for 3 months; with X-rays performed at 1, 2, 4, 6, 10, and 12 weeks, and magnetic resonance imaging (MRI) scans at 4 and 12 weeks. Disk height change was evaluated by calculating the disk height index (DHI) on X-rays. In each animal, a baseline DHI was calculated based on the rostral healthy disc. Disk degeneration grade was also evaluated on T2-weighted MRI sequences based on the signal change in the annulus fibrosus and nucleus pulposus. A 1-4 modified Thompson grading system was used, defined as no, mild, moderate, and severe degeneration. Statistical analysis was performed in all animals and in the two different groups. Results On X-rays, the mean disk height in all 13 rats showed significant decrease at both 1 week and 2 weeks, with the maximum decrease observed at 2 weeks. The disk height increased gradually between 4 to 12 weeks; however it was not statistically significant. In the separate analysis of the two different groups, the second group had a similar significant decrease in disk height at 1 and 2 weeks. Despite minor changes, in the first group no statistical significance was detected. On T2-weighted MRI scans at 4 and 12 weeks, all rats had a statistically significant increase in disk degeneration grade, as compared to the baseline. However, the minor increase in degeneration grade between 4 weeks to 12 weeks was not statistically significant. On separate analysis, only the second group indicated significant increase in the disk degeneration grade after the puncture experience. The X-Ray results presented as DHIs and the MRI results described as the 1-4 modified Thompson grading system for intervertebral disk degeneration showed strong correlation in all 13 rats, and in each of the 2 groups separately. Conclusion Isolated needle puncturing of the intervertebral disk leads to significantly lower levels of degeneration compared to needle puncturing followed by further manual mechanical manipulation. The highest level of degeneration is observed at 2 weeks. Disk height decrease on X-Ray imaging and signal changes on T2-weighted MRI scans can provide good informative data on the level of degeneration. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared

Intervertebral disc (IVD) degeneration is driven by a vicious circle of interrelated biological and biomechanical factors. Dynamic unloading, defined as dynamic partial decompression, promotes water and metabolite flow, which is essential for IVD homeostasis. However, the mechanobiological effects of unloading remain poorly understood. IVD organ cultures offer a valuable model for studying IVD degeneration and regeneration at the molecular level. This study investigated the biological and biomechanical effects of induced degeneration and the subsequent short-term dynamic unloading of bovine tail IVDs in a bioreactor culture system. We applied a one-strike degenerative trigger on Day 0 and assessed its immediate effects after 1 day of culture under bioreactor loading (Timepoint 1). The impact of dynamic unloading for three additional days (Timepoint 2) was evaluated in comparison to continued loading. We evaluated biological outcomes, namely cell viability, gene expression, water/sulfated glycosaminoglycan (sGAG) ratio, and sGAG release. Mechanical readouts included disc height, slope of the elastic zone, area under the curve, and neutral zone characteristics. On Timepoint 1, we demonstrated degeneration in the nucleus pulposus with altered viability, increased inflammatory and catabolic gene expression, elevated sGAG release, a decreased slope of the elastic zone, and an increased area under the curve. On Timepoint 2, we noticed a sustained degenerative cascade in both degeneration groups. However, unloading showed a trend towards partial mitigation of the induced degeneration with decreased iNOS and TRPV4 expression, an increased water/sGAG ratio, reduced sGAG release, and recovery of the disc height. This first exvivo study on unloading mechanobiology of bovine degenerated IVDs unveils encouraging preliminary insights. The findings suggest potential benefits of unloading and, more broadly, therapeutic movement as regenerative strategies for degenerated IVDs. These results underscore the need for further studies and encourage research combining mechanical and biological approaches in organ culture models.

Sagittal plane motion in the human lumbar spine: Comparison of the in vitro quasistatic neutral zone and dynamic motion parameters

Appropriate animal models of disc degeneration are critical for the study of proposed interventions as well as to further delineate the degenerative process. The purpose of this study was to characterize a porcine model for disc degeneration confirmed on magnetic resonance (MR) imaging studies and histological analysis. Twelve miniature pigs were used (weight 48-65 kg) to study degeneration in the lumbar spine. Under fluoroscopic guidance, the disc was percutaneously punctured with a 3.2-mm-diameter trephine to a 5-mm depth into the annulus fibrosus. Control and experimental levels were randomized among 6 levels in the lumbar spine. The unlesioned spinal levels were used as controls and were compared with lesioned levels. Magnetic resonance imaging grading and disc height were serially recorded preoperatively, and at 5, 8, 19, 32, and 39 weeks postoperatively. The animals were killed in groups of 3 at 7, 18, 32, and 41 weeks postinjury, and the discs were examined histopathologically. Consistent, sequential, and progressive degeneration of the annular injury was observed on MR imaging and histopathological studies from the time of injury to the final time point. The disc height and the disc height index also sequentially decreased from the time of the injury in a consistent manner. The uninjured control levels did not show any progressive degeneration and maintained their normal state. Based on MR imaging and histopathological findings, the authors demonstrated and characterized a reliable model of sequential disc degeneration in miniature pigs with percutaneous injury to the annulus fibrosus. In the early stages, as soon as 5 weeks after injury, significant disc degeneration was seen on MR imaging grading with decreases in disc height. This degeneration did not improve by the final time point of 39 weeks.

In bilateral cervical facet dislocation, biomechanical stabilities between anterior locking screw/plate fixation after anterior cervical discectomy and fusion (ACDFP) and posterior transpedicular screw/rod fixation after anterior cervical discectomy and fusion (ACDFTP) have not been compared using the human cadaver, although ACDFP has been performed frequently. In this study the stability of ACDFP, a posterior wiring procedure after ACDFP (ACDFPW), and ACDFTP for treatment of bilateral cervical facet dislocation were compared. Spines (C3-T1) from 10 human cadavers were tested in the intact state, and then after ACDFP, ACDFPW, and ACDFTP were performed. Intervertebral motion was measured using a video-based motion capture system. The range of motion (ROM) and neutral zone (NZ) were compared for each loading mode to a maximum of 2 Nm. The ROM for spines treated with ACDFP was below that of the intact spine in all loading modes, with statistical significance in flexion and extension, but NZs were decreased in flexion and extension and slightly increased in bending and axial rotation; none of these showed statistical significance. The ACDFPW produced statistically significant additional stability in axial rotation ROM and in flexion NZ than ACDFP. The ACDFTP provided better stability than ACDFP in bending and axial rotation, and better stability than ACDFPW in bending for both ROM and NZ. There was no significant difference in extension with either ROM or NZ for the three fixation methods. The spines treated with ACDFTP demonstrated the most effective stabilization, followed by those treated with ACDFPW, and then ACDFP. The spines receiving ACDFP also revealed a higher stability than the intact spine in most loading modes; thus ACDFP can also provide a relatively effective stabilization in bilateral cervical facet dislocation, but with the aid of a brace.

Objectives To compare the biomechanical stability of two-level PLIF constructs with unilateral and bilateral pedicle screw fixations. Methods Six cadaveric lumbar segments were evaluated to assess biomechanical stability in response to pure moment loads applied in flexion-extension (FE), lateral bending (LB), and axial rotation (AR). Each specimen was tested in six sequential configurations: (1) intact baseline; (2) facetectomy; (3) unilateral pedicle screws (UPS); (4) bilateral pedicle screws (BPS); (5) unilateral pedicle screws and cage (UPSC); and (6) bilateral pedicle screws and cage (BPSC). Results Significant reductions in motion were observed when comparing all instrumented conditions to the intact and facetectomy stages of testing. No significant differences in motion between UPS, BPS, UPSC, or BPSC were observed in response to FE range of motion (ROM) or neutral zone (NZ). ROM was significantly higher in the UPS stage compared to BPS in response to LB and AT loading. ROM was significantly higher in UPSC compared to BPSC in response to LB loading only. Similarly, NZ was significantly higher in UPSC compared to BPSC in response to only LB loading. In response to AT loading, ROM was significantly higher during UPS than BPS or BPSC; however, no significant differences were noted between UPSC and BPSC with respect to AT ROM or NZ. Conclusion BPS fixation is biomechanically superior to UPS fixation in multilevel PLIF constructs. This was most pronounced during both LB loading. Interbody support did contribute significantly to immediate stability.

An in vitro biomechanical investigation using human lumbar cadaveric spine specimens was undertaken to determine any relationship between intervertebral disc degeneration and nonlinear multidirectional spinal flexibility. Previous clinical and biomechanical studies have not established conclusively such a relationship. Forty-seven discs from 12 whole lumbar spine specimens were studied under the application of flexion-extension, axial rotation, and lateral bending pure moments. Three flexibility parameters were defined (neutral zone (NZ), range of motion (ROM), and neutral zone ratio (NZR = NZ/ROM)) and correlated with the macroscopic and radiographic degeneration. In flexion-extension, the ROM decreased and NZR increased with degeneration. In axial rotation, NZ and NZR increased with degeneration. In lateral bending, the ROM significantly decreased and the NZR increased with degeneration. In all three loading directions, the NZR increased, indicating greater joint laxity with degeneration.

In vitro evaluation of a chemical, injectable intervention for discectomy induced destabilization. To investigate the ability of two collagen crosslinking agents to restore mechanical properties to lumbar joints destabilized by surgical decompression procedures. Posterior decompression surgery is a common procedure indicated for tissue pathology that interferes with surrounding neural structures. Previous in vitro, analytical, and clinical studies have shown that removal of load-supporting tissue can compromise joint stability mandating some form of postsurgical stabilization. Currently, no nonsurgical treatments are capable of restoring stability and preventing subsequent degeneration. Exogenous crosslinking of intact discs has shown a fourfold increase in joint stability. Fifteen bovine lumbar intervertebral joints were randomly separated into methylglyoxal or genipin treatment groups. Flexion-extension flexibility was quantified in three conditions: intact, postdecompression surgery, and after crosslinking reagent injections. Instability was quantified by calculating neutral zone (NZ), percentage of hysteresis, range of motion, and percentage of strain energy. Simulated surgical decompression increased NZ 111% (P = 0.009), 28% (P = 0.004), range of motion 57% (P = 0.003), and decreased strain energy 37% (P = 0.004). For those discs undergoing methylglyoxal treatment NZ was subsequently reduced 68% (P = 0.012), hysteresis 28% (P = 0.018), range of motion 29% (P = 0.012), and strain energy was increased 71% (P = 0.018). For discs subjected to genipin treatment, NZ was reduced 52% (P = 0.018), hysteresis 23% (P = 0.012), range of motion 44% (P = 0.017), and strain energy was increased 66% (P = 0.012). Mean NZ was lower than intact mean after both methylglyoxal and genipin treatments, 10% and 17% less, respectively, but these differences were not significant. Mean values for all other parameters posttreatment were within 6% of the corresponding intact mean values. Injections of crosslinking reagents into lumbar intervertebral discs after simulated decompression surgery restored joint stability according to all parameters. Similar results were found for genipin and methylglyoxal reagents. Implementing exogenous collagen crosslinking as an adjunct to current surgical decompression procedures may be beneficial in preventing or delaying subsequent spinal instability and degeneration.

Lumbar segmental instability: Points to ponder

Instability of the cervical spine following whiplash trauma has been demonstrated in a number of studies. We hypothesized that, in patients with whiplash-associated disorder, rotation of the head would be accompanied by an earlier onset of neck muscle activity to compensate for intrinsic instability. The aim of the study was to examine the range of motion (RoM) of the cervical spine and the onset and activity of the sternocleidomastoid (SCM) muscles during axial rotation, in healthy control subjects and in patients with chronic whiplash-associated disorder. Forty-eight control subjects (42% male) and 46 patients (33% male) with chronic whiplash-associated disorder (symptoms lasting longer than 3 months) were examined. Cervical axial RoM differed significantly (P = 0.0001) between the groups, with the whiplash patients showing lower values (83 degrees +/- 30 degrees) than the healthy controls (137 degrees +/- 19 degrees). The whiplash patient group showed no evidence of the predicted earlier activation of SCM muscles. Many patients never reached the point in the RoM where SCM muscle activity rises steeply, as it does in the healthy controls (the 'elastic zone'), and their movements remained mostly within the region of low muscle activity (the 'neutral zone'). The whiplash patients appeared either unable or unwilling to drive the cervical spine into this region of high muscle activity, possibly because they were restricted by existing pain or fear of pain.

Employing a precise measurement protocol, it was investigated whether decreased height of lumbar discs is related to an increase of sagittal plane segmental motion or to a displacement of the cranial vertebra into a retrolisthesis position. The height of the intervertebral discs, the dorsoventral displacement of the cranial vertebra and the range of sagittal plane rotational and transitional motion were measured for all segments of the lumbar spine from flexion-extension views of 30 patients. In each patient, at least one lumbar disc exhibited a significant height decrease. The measurement was performed using a new protocol compensating for distortion in central projection, off-centre position, axial rotation and lateral tilt of the spine. Measured data on retrolisthesis position, rotational and translational motion were compared with previously compiled age- and gender-appropriate normal data. In the cohort investigated there was no statistically significant relation between a decrease of disc height and segmental hypermobility with respect to sagittal plane rotation or translation. There was no relation between a decrease of disc height and a displacement of the adjacent cranial vertebra into a retrolisthesis position. The results challenge the often postulated relation between low disc height and segmental hypermobility ("instability") and retrolisthesis position of the cranially adjacent vertebra.

Biomechanical properties of intact spinal motion segments are used to establish baseline values during in vitro studies evaluating spinal surgical techniques and implants. These properties are also used to validate computational models (ie, patient-specific finite element models) of human lumbar spine segments. Our laboratory has performed a large number of in vitro mechanical studies of lumbar spinal segments, using a consistent methodology. This provides extensive biomechanical data for a large number of intact motion segments, along with donor demographic variables, bone mineral density (BMD) measurements, and geometric properties. The objective of this study was to analyze how donor demographics, BMD, and geometric properties of cadaveric lumbar spine segments affect motion segment flexibility, including the range of motion (ROM), lax zone (LZ), and stiff zone (SZ), to help improve our understanding of spinal biomechanics. A retrospective study examined the relationships between the biomechanical properties of 281 lumbar motion segments from 85 human cadaveric spines, donor demographic variables (age, sex, weight, height, and body mass index), and specimen measurements (vertebral body height, intervertebral disc height, and BMD). Statistical correlation and regression analyses showed that the flexibility of a lumbar motion segment is affected by lumbar level, donor age, sex, and weight as well as the intervertebral disc height, vertebral body height, and bone quality. Increased disc height was associated with decreased ROM (axial rotation), decreased LZ (flexion-extension and axial rotation), and increased SZ (flexion-extension and lateral bending) in the male group, but increased ROM (lateral bending) in the female group. Increased vertebral body height correlated with increased LZ (lateral bending) in the female group. Increased BMD correlated with decreased ROM overall. Biomechanical measurements from flexibility testing of cadaveric lumbar spine segments are significantly correlated with donor demographics and specimen measurements. Many of these correlations are sex-dependent.

Cervical spine instability following axial compression injury: A biomechanical study