Christopher Daly

A Review of Animal Models of Intervertebral Disc Degeneration: Pathophysiology, Regeneration, and Translation to the Clinic

Lower back pain is the leading cause of disability worldwide. Discogenic pain secondary to intervertebral disc degeneration is a significant cause of low back pain. Disc degeneration is a complex multifactorial process. Animal models are essential to furthering understanding of the degenerative process and testing potential therapies. The adult human lumbar intervertebral disc is characterized by the loss of notochordal cells, relatively large size, essentially avascular nature, and exposure to biomechanical stresses influenced by bipedalism. Animal models are compared with regard to the above characteristics. Numerous methods of inducing disc degeneration are reported. Broadly these can be considered under the categories of spontaneous degeneration, mechanical and structural models. The purpose of such animal models is to further our understanding and, ultimately, improve treatment of disc degeneration. The role of animal models of disc degeneration in translational research leading to clinical trials of novel cellular therapies is explored.

Ovine lumbar intervertebral disc degeneration model utilizing a lateral retroperitoneal drill bit injury

Intervertebral disc degeneration is a significant contributor to the development of back pain and the leading cause of disability worldwide. Numerous animal models of intervertebral disc degeneration have been developed. The ideal animal model should closely mimic the human intervertebral disc with regard to morphology, biomechanical properties and the absence of notochordal cells. The sheep lumbar intervertebral disc model fulfils these criteria. We present an ovine model of intervertebral disc degeneration utilizing a drill bit injury through a lateral retroperitoneal approach. The lateral approach significantly reduces the incision and potential morbidity associated with the traditional anterior approach to the ovine spine. Utilization of a drill-bit method of injury affords the ability to produce a consistent and reproducible injury, of precise dimensions, that initiates a consistent degree of intervertebral disc degeneration. The focal nature of the annular and nucleus pulposus defect more closely mimics the clinical condition of focal intervertebral disc herniation. Sheep recover rapidly following this procedure and are typically mobile and eating within the hour. Intervertebral disc degeneration ensues and sheep undergo necropsy and subsequent analysis at periods from eight weeks. We believe that the drill bit injury model of intervertebral disc degeneration offers advantages over more conventional annular injury models.

Perioperative care for lumbar microdiscectomy: a survey of Australasian neurosurgeons

Background Lumbar microdiscectomy is the most commonly performed spine surgery procedure. Over time it has evolved to a minimally invasive procedure. Traditionally patients were advised to restrict activity following lumbar spine surgery. However, post-operative instructions are heterogeneous. The purpose of this report is to assess, by survey, the perioperative care practices of Australasian neurosurgeons in the minimally invasive era. Methods A survey was conducted by email invitation sent to all full members of the Neurosurgical Society of Australasia (NSA). This consisted of 11 multi-choice questions relating to operative indications, technique, and post-operative instructions for lumbar microdiscectomy answered by an electronically distributed anonymized online survey. Results The survey was sent to all Australasian Neurosurgeons. In total, 68 complete responses were received (28.9%). Most surgeons reported they would consider a period of either 4 to 8 weeks (42.7%) or 8 to 12 weeks (32.4%) as the minimum duration of radicular pain adequate to offer surgery. Unilateral muscle dissection with unilateral discectomy was practiced by 76.5%. Operative microscopy was the most commonly employed method of magnification (76.5%). The majority (55.9%) always refer patients to undergo inpatient physiotherapy. Sitting restrictions were advised by 38.3%. Lifting restrictions were advised by 83.8%. Conclusions Australasian neurosurgical lumbar microdiscectomy perioperative care practices are generally consistent with international practices and demonstrate a similar degree of heterogeneity. Recommendation of post-operative activity restrictions by Australasian neurosurgeons is still common. This suggests a role for the investigation of the necessity of such restrictions in the era of minimally invasive spine surgery.

A Comparison of Two Ovine Lumbar Intervertebral Disc Injury Models for the Evaluation and Development of Novel Regenerative Therapies

Study Design: Large animal research. Objective: Lumbar discectomy is the most commonly performed spinal surgical procedure. We investigated 2 large animal models of lumbar discectomy in order to study the regenerative capacity of mesenchymal stem cells following disc injury. Methods: Twelve adult ewes underwent baseline 3-T magnetic resonance imaging (MRI) followed by lumbar intervertebral disc injury by either drill bit (n = 6) or annulotomy and partial nucleotomy (APN) (n = 6). Necropsies were performed 6 months later. Lumbar spines underwent 3-T and 9.4-T MRI prior to histological, morphological and biochemical analysis. Results: Drill bit-injured (DBI) and APN-injured discs demonstrated increased Pfirrmann grades relative to uninjured controls (P < .005), with no difference between the 2 models. Disc height index loss was greater in the APN group compared with the DBI group (P < .005). Gross morphology injury scores were higher in APN than DBI discs (P < .05) and both were higher than controls (P < .005). Proteoglycan was reduced in the discs of both injury models relative to controls (P < .005), but lower in the APN group (P < .05). Total collagen of the APN group disc regions was higher than DBI and control discs (P < .05). Histology revealed more matrix degeneration, vascular infiltration, and granulation in the APN model. Conclusion: Although both models produced disc degeneration, the APN model better replicated the pathobiology of human discs postdiscectomy. We therefore concluded that the APN model was a more appropriate model for the investigation of the regenerative capacity of mesenchymal stem cells administered postdiscectomy.

Indications for Use of Dynamic Four-dimensional Computed Tomography in Diagnosing Instability in Spinal Cervical Conditions

Introduction Cervical spinal instability is a pathological consequence of a variety of spine disorders such as trauma, malignancy and degenerative conditions. If left undiagnosed, cervical spinal instability can lead to compressive cervical myelopathy and devastating consequences such as quadriplegia and death. Although dynamic cervical X-ray is traditionally used to detect cervical instability, it provides only two static views and there is no gold standard in diagnosing such condition. Dynamic four-dimensional computed tomography (4DCT) is a non-invasive method that provides functional assessment of cervical motion in high resolution, throughout the entire range of motion. It has been previously shown to be clinically useful in assessing instability and impingement evaluation of the shoulder and finger joint. This is the first early case series utilizing dynamic 4DCT to assess cervical instability in various spinal pathologies. Material and Methods Six elderly patients who presented with neck pain and suspected instability in cervical spine from a major Australian academic hospital were included. In addition to routine imaging modalities, dynamic 4DCT of cervical spine was performed using a 320 × 0.5mm detector multislice-CT (Aquilion One, Toshiba Medical Systems, Japan) with consent. With gantry rotation speed of 275 milliseconds, scans were conducted without table motion with patients in the lateral-decubitus position, capturing approximately seven volume datasets per second. Patients were instructed to continuously move their necks between flexion and extension. Cine movie files were generated from the volume datasets. Results The mean age of the cohort was 69 years old. There was equal male:female ratio. All patients presented with neck pain. Two presented acutely after trauma: one with suspected ligamentous instability at C1/C2; the second presented after recurrent falls with suspected fracture of odontoid process. Four patients had neck pain of more than 6 months at presentation: one had severe rheumatoid arthritis with suspected C1/C2 instability; three patients had cervical spondylotic changes, with one having had a previous anterior cervical discectomy and fusion(ACDF). Before employing 4DCT, MRI and static CT of occipito-cervical regions were performed in five patients; dynamic X-ray of cervical spine at flexion and extension were performed in four patients. Interpretation of the imaging finding in all cases by neuroradiologist and neurosurgeon was found to be equivocal for stability. Dynamic 4DCT confidently ruled in or ruled out cervical spinal instability in all cases: one case was confirmed to have instability; five cases were confirmed to be stable. The one unstable case with severe cervical spondylosis was demonstrated on 4DCT to have instability at C3/C4 level and incomplete fusion from previous ACDF at C5/C6 level and a cervical stabilization procedure was offered. The remaining stable cases included all the trauma cases with a case of os odontoideum diagnosed on 4DCT. Conservative management was prescribed confidently Conclusion Dynamic 4DCT can be used to detect and confirm subtle cervical spinal instability (or lack thereof) with relative ease in various cervical spinal pathologies such as rheumatoid arthritis, cervical spondylosis, os odontoideum and trauma. We propose that dynamic 4DCT has an important role in detecting cervical spinal stability and further studies using this technique are warranted.