Search

Low back pain (LBP) is often associated with the degeneration of human intervertebral discs (IVDs). However, the pain-inducing mechanism in degenerating discs remains to be elucidated. Here, we identified a subtype of locally residing nucleus pulposus cells (NPCs), generated by the environmental stress in degenerating discs, that triggered the onset of discogenic LBP. Single-cell transcriptomic analysis of human tissues showed a strong correlation between this specific pain-triggering subtype and the pain conditions in human degenerated discs. Next, we recreated this pain-triggering subtype by applying known exogenous stressors to healthy NPCsin vitro. The recreated pain phenotype activated functional sensory neurons responsein vitroand induced local inflammatory responses, hyperalgesia, and mechanical sensitivity in a healthy rat IVDin vivo. Our findings provide strong evidence of a previously unknown pain-inducing mechanism mediated by NPCs in degenerating IVDs. This newly defined pathway will aid in the development of NPC-targeted therapeutic strategies for clinically unmet need to attenuate discogenic LBP.One Sentence SummaryDiscogenic low back pain can be initiated by a stress-induced subtype of nucleus pulposus cells present in human degenerating intervertebral discs

BACKGROUND CONTEXT Nonphysiological mechanical loading and inflammation are both critically involved in intervertebral disc (IVD) degeneration, which is characterized by an increase in cytokines and matrix metalloproteases (MMPs) in the nucleus pulposus (NP). This process is known to be mediated by the NF-κB pathway. CLINICAL SIGNIFICANCE Current clinical treatments for IVD degeneration focus on the alleviation of symptoms rather than targeting the underlying mechanism. Injection of an NF-κB inhibitor may attenuate the progression of IVD degeneration. PURPOSE To investigate the ability of the NF-κB inhibitor, NEMO binding domain peptide (NBD), to alter IVD degeneration processes by reducing IL-1β- and mechanically-induced cytokine and MMP levels in human nucleus pulposus cells in vitro, and by attenuating IVD degeneration in an in vivo rat model for disc degeneration. STUDY DESIGN Experimental in vitro and animal model. PATIENT SAMPLE Discarded specimens of lumbar disc from 21 patients, and 12 Sprague Dawley rats. OUTCOME MEASURES Gene and protein expression, cell viability, µMRI and histology. METHODS IL-1β-prestimulated human nucleus pulposus cells embedded into fibrin constructs were loaded in the Flexcell FX-5000 compression system at 5 kPa and 1 Hz for 48 hours in the presence and absence of NBD. Unloaded hNPC/fibrin constructs served as controls. Cell viability in loaded and unloaded constructs was quantified, and gene and protein expression levels determined. For in vivo testing, a rat needle disc puncture model was employed. Experimental groups included injured discs with and without NBD injection and uninjured controls. Levels of disc degeneration were determined via µMRI, qPCR and histology. Funding sources include $48,874 NASS Young Investigator Research Grant and $119,174 NIH 5K01AR071512-02. There were no applicable financial relationships or conflicts of interest. RESULTS Mechanical compression of hNPC/fibrin constructs resulted in upregulation of MMP-3 and IL-8. Supplementation of media with 10 μM NBD during loading increased cell viability, and decreased MMP-3 gene and protein levels. IVD injury in rat resulted in an increase in MMP-3, IL-1β and IL-6 gene expression. Injections of 250 µg of NBD during disc injury resulted in decreased IL-6 gene expression. µMRI analysis demonstrated a reduction of disc hydration in response to disc needle injury, which was attenuated in NBD-treated IVDs. Histological evaluation showed NP and AF lesion in injured discs, which was attenuated by NBD injection. CONCLUSIONS The results of this study show NBD peptide's capacity to reduce IL-1β- and loading-induced MMP-3 levels in hNPC/fibrin constructs while increasing the cells’ viability, and to attenuate IVD degeneration in rat, involving downregulation of IL-6. Therefore, NBD may be a potential therapeutic agent to treat IVD degeneration.

Study Design Retrospective cohort study Objectives To describe the common types of complications and their risk factors during spine surgery in patients with achondroplasia. Methods A retrospective review was performed of medical records of adult achondroplasia patients who underwent spine surgery at our institution between 2007 and 2021. Inclusion criteria were achondroplasia and age >16 years. Surgical encounters were evaluated for durotomy, postoperative neurologic deficit, wound compromise, medical complications, and return to the operating room. Statistical analysis included evaluation of relationships across complications and fisher exact test applied to bivariate/categorical variables and t-test/ANOVA for continuous variables. Multivariable analysis using logistic regression was performed to account for patient characteristics Results Fifty-five patients with achondroplasia underwent 95 surgeries. Forty-nine percent of the surgeries involved a complication. These included durotomy (33.7%), neurologic deficit (11.6%), wound compromise (6.3%), and other medical complications (6.3%). Thirteen percent of surgeries required return to the operating room. The greatest number of complications occurred in thoracolumbar region (60.0%) compared to cervicothoracic (18.2%) and craniocervical junction (33.3%). Chronologically later surgical encounters had decreased complications and durotomies only occurred in thoracolumbar surgeries (45.7%). Conclusions Adult patients with achondroplasia undergoing surgery chronologically later in this set of consecutive patients were at a decreased risk for complications. Thoracolumbar surgeries were at the greatest risk for durotomies. Male sex was a risk factor for durotomy, while age was a risk factor for neurologic deficit. The potential for adverse surgical events should be considered when evaluating patients with achondroplasia for spine surgery.

BACKGROUND Patients who survive traumatic atlanto-occipital dissociation (AOD) may present with normal neurological examinations and near-normal-appearing diagnostic images, such as cervical radiographs and computed tomography (CT) scans. OBSERVATIONS The authors described a neurologically intact 64-year-old female patient with a degenerative autofusion of her right C4–5 facet joints who presented to their center after a motor vehicle collision. Prevertebral soft tissue swelling and craniocervical subarachnoid hemorrhage prompted awareness and consideration for traumatic AOD. An abnormal occipital condyle–C1 interval (4.67 mm) on CT and craniocervical junction ligamentous injury on magnetic resonance imaging (MRI) confirmed the diagnosis of AOD. Her autofused right C4–5 facet joints were incorporated into the occipitocervical fusion construct. LESSONS Traumatic AOD can be easily overlooked in patients with a normal neurological examination and no associated upper cervical spine fractures. A high index of suspicion is needed when evaluating CT scans because normal values for craniocervical parameters are significantly different from the accepted ranges of normal on radiographs in the adult population. MRI of the cervical spine is helpful to evaluate for atlanto-occipital ligamentous injury and confirm the diagnosis. Occipitocervical fusion construct may need to be extended to incorporate spinal levels with degenerative autofusion to prevent adjacent level degeneration.

Background Subependymomas are rare in the spinal cord. They are typically expansile, intramedullary spinal cord masses, eccentrically located with minimal gadolinium enhancement. Case Description We present a case of subependymoma originating from the cervical cord with an unusual exophytic appearance. Hallmarks of subependymoma and treatment are reviewed. Conclusions This is the first case, to our knowledge, where imaging revealed a mass appearing to be completely extramedullary with a primary exophytic component. Therefore, subependymomas should remain on the differential for masses in the spinal cord that appear extramedullary and exophytic.

BACKGROUND Cervical spine surgery sometimes necessitates complex ventral/dorsal approaches or osteotomies that place the vertebral artery (VA) at risk of inadvertent injury. Tortuosity of the VA poses increased risk of vessel injury during anterior decompression or placement of posterior instrumentation. OBSERVATIONS In this report, the authors describe a patient with degenerative cervical spondylotic myelopathy and focal kyphotic deformity requiring corrective surgery via a combined ventral/dorsal approach. Computed tomography (CT) and CT angiography (CTA) of the spine identified a left medially enlarged C4 transverse foramen and tortuous VA V2 segment forming a potentially dangerous medial loop into the vertebral body, respectively. The patient’s presentation and management are described. LESSONS The course of the VA is variable, and a tortuous VA with significant medial or lateral displacement may be dangerous during ventral and dorsal approaches to the cervical spine. CTA of the cervical spine is warranted in cases in which atlantoaxial fixation is needed or suspicious transverse foramen morphology is identified to understand the course of the VA and identify anatomical variations that would put the VA at risk during cervical spine surgery.

We describe non-operative management a rare traumatic clival fracture extending through the bilateral occipital condyles. Clinical History: A 26-year-old female who was involved in a high-speed motor vehicle crash presented to an outside facility with difficulty speaking. Subsequent CT of the cervical spine demonstrated a fracture of the clivus with extension through the bilateral occipital condyles. She was then transferred to our hospital for further management where complete trauma survey noted multiple other injuries including traumatic subarachnoid hemorrhage, spinal epidural hematoma, bilateral pneumothoraces, liver laceration, bilateral upper extremity injuries, and lumbosacral fractures. Additional spinal imaging was negative for any associated vascular or spinal cord injury. Given her young age, there was a strong interest to preserve craniocervical motion and the decision was made to treat her with non-operatively with halo placement. After 18 weeks of rigid fixation, follow up imaging demonstrated completely healed fractures and at twenty-one weeks post fixation she demonstrated preserved motion of the craniocervical junction. This is a review of the literature and case report regarding this rare entity and its management.

Anterior lumbar approaches have historically been regarded as maximally invasive. However, with the advent of well-trained vascular surgeons to do the approaches through smaller incisions and with decreased operative time, anterior lumbar approaches are becoming more widely utilized. Stand-alone lumbar interbody fusions and artificial disc replacements are two of the mainstay procedures for this approach. This chapter will give an overview of the procedure and nuances to consider along the way.

Background: Multiple radiation-induced cavernous malformations of the cauda equina are extremely rare. A review of the literature suggested that the post-irradiation lumbosacral radiculopathy in our patient was most likely associated with a diagnosis of multiple radiation-induced cavernous malformations of the cauda equina. Case Description: A 76-year-old man with a remote history of abdominal radiation therapy presented with a 6-month history of progressively worsening right foot drop and balance impairment. Magnetic resonance imaging (MRI) revealed multiple enhancing areas of the cauda equina concerning for carcinomatous meningitis, however, cerebrospinal fluid (CSF) analysis was unrevealing. Intraoperative findings were consistent with multiple radiation-induced cavernous malformations of the cauda equina. Conclusions: Multiple radiation-induced cavernous malformations of the cauda equina may mimic carcinomatous or infectious meningitis. Clinicians should be suspicious of this diagnosis when CSF and MRI findings are inconsistent with metastatic disease or infectious meningitis in patients who present with radiculopathy and a history of radiation therapy.

Object Classic biomechanical models have used thoracic spines disarticulated from the rib cage, but the biomechanical influence of the rib cage on fracture biomechanics has not been investigated. The well-accepted construct for stabilizing midthoracic fractures is posterior instrumentation 3 levels above and 2 levels below the injury. Short-segment fixation failure in thoracolumbar burst fractures has led to kyphosis and implant failure when anterior column support is lacking. Whether shorter constructs are viable in the midthoracic spine is a point of controversy. The objective of this study was the biomechanical evaluation of a burst fracture at T-9 with an intact rib cage using different fixation constructs for stabilizing the spine. Methods A total of 8 human cadaveric spines (C7–L1) with intact rib cages were used in this study. The range of motion (ROM) between T-8 and T-10 was the outcome measure. A robotic spine testing system was programmed to apply pure moment loads (± 5 Nm) in lateral bending, flexion-extension, and axial rotation to whole thoracic specimens. Intersegmental rotations were measured using an optoelectronic system. Flexibility tests were conducted on intact specimens, then sequentially after surgically induced fracture at T-9, and after each of 4 fixation construct patterns. The 4 construct patterns were sequentially tested in a nondestructive protocol, as follows: 1) 3 above/2 below (3A/2B); 2) 1 above/1 below (1A/1B); 3) 1 above/1 below with vertebral body augmentation (1A/1B w/VA); and 4) vertebral body augmentation with no posterior instrumentation (VA). A repeated-measures ANOVA was used to compare the segmental motion between T-8 and T-10 vertebrae. Results Mean ROM increased by 86%, 151%, and 31% after fracture in lateral bending, flexion-extension, and axial rotation, respectively. In lateral bending, there was significant reduction compared with intact controls for all 3 instrumented constructs: 3A/2B (−92%, p = 0.0004), 1A/1B (−63%, p = 0.0132), and 1A/1B w/VA (−66%, p = 0.0150). In flexion-extension, only the 3A/2B pattern showed a significant reduction (−90%, p = 0.011). In axial rotation, motion was significantly reduced for the 3 instrumented constructs: 3A/2B (−66%, p = 0.0001), 1A/1B (−53%, p = 0.0001), and 1A/1B w/VA (−51%, p = 0.0002). Between the 4 construct patterns, the 3 instrumented constructs (3A/2B, 1A/1B, and 1A/1B w/VA) showed comparable stability in all 3 motion planes. Conclusions This study showed no significant difference in the stability of the 3 instrumented constructs tested when the rib cage is intact. Fractures that might appear more grossly unstable when tested in the disarticulated spine may be bolstered by the ribs. This may affect the extent of segmental spinal instrumentation needed to restore stability in some spine injuries. While these initial findings suggest that shorter constructs may adequately stabilize the spine in this fracture model, further study is needed before these results can be extrapolated to clinical application.

This paper provides a detailed report of the "First Annual Spinal Navigation, Emerging Technologies and Systems Integration" meeting held December 3, 2016 at the Seattle Science Foundation.

Classic biomechanical models have used thoracic spines disarticulated from the rib cage, but the biomechanical influence of the rib cage on fracture biomechanics has not been investigated. The well-accepted construct for stabilizing midthoracic fractures is posterior instrumentation 3 levels above and 2 levels below the injury. Short-segment fixation failure in thoracolumbar burst fractures has led to kyphosis and implant failure when anterior column support is lacking. Whether shorter constructs are viable in the midthoracic spine is a point of controversy. The objective of this study was the biomechanical evaluation of a burst fracture at T-9 with an intact rib cage using different fixation constructs for stabilizing the spine.A total of 8 human cadaveric spines (C7-L1) with intact rib cages were used in this study. The range of motion (ROM) between T-8 and T-10 was the outcome measure. A robotic spine testing system was programmed to apply pure moment loads (± 5 Nm) in lateral bending, flexion-extension, and axial rotation to whole thoracic specimens. Intersegmental rotations were measured using an optoelectronic system. Flexibility tests were conducted on intact specimens, then sequentially after surgically induced fracture at T-9, and after each of 4 fixation construct patterns. The 4 construct patterns were sequentially tested in a nondestructive protocol, as follows: 1) 3 above/2 below (3A/2B); 2) 1 above/1 below (1A/1B); 3) 1 above/1 below with vertebral body augmentation (1A/1B w/VA); and 4) vertebral body augmentation with no posterior instrumentation (VA). A repeated-measures ANOVA was used to compare the segmental motion between T-8 and T-10 vertebrae.Mean ROM increased by 86%, 151%, and 31% after fracture in lateral bending, flexion-extension, and axial rotation, respectively. In lateral bending, there was significant reduction compared with intact controls for all 3 instrumented constructs: 3A/2B (-92%, p = 0.0004), 1A/1B (-63%, p = 0.0132), and 1A/1B w/VA (-66%, p = 0.0150). In flexion-extension, only the 3A/2B pattern showed a significant reduction (-90%, p = 0.011). In axial rotation, motion was significantly reduced for the 3 instrumented constructs: 3A/2B (-66%, p = 0.0001), 1A/1B (-53%, p = 0.0001), and 1A/1B w/VA (-51%, p = 0.0002). Between the 4 construct patterns, the 3 instrumented constructs (3A/2B, 1A/1B, and 1A/1B w/VA) showed comparable stability in all 3 motion planes.This study showed no significant difference in the stability of the 3 instrumented constructs tested when the rib cage is intact. Fractures that might appear more grossly unstable when tested in the disarticulated spine may be bolstered by the ribs. This may affect the extent of segmental spinal instrumentation needed to restore stability in some spine injuries. While these initial findings suggest that shorter constructs may adequately stabilize the spine in this fracture model, further study is needed before these results can be extrapolated to clinical application.