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Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_III | Pages 434 - 435
1 Sep 2009
Vernon-Roberts B Moore R Fraser R
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Introduction: The age-related reduction of water-trapping proteoglycans needed to maintain optimal disc hydration may be caused by reduced synthetic ability or fewer chondrocytes but there is a paucity of objective quantitative studies of disc cellularity.

Methods: Sagittal sections of L4–5 discs were subdivided into a nucleus zone and 18 annulus zones prior to determining cell density (cells/mm2) in

the mid-sagittal plane of 10 male and 10 female discs aged 13–79 years;

7 parasagittal slices through a single disc;

discs showing various types of tears.

Results:

Most chondrocytes were unicellular but bicellular and multicellular chondrons were common in the margins of large tears and the nucleus in degenerate discs.

Cellularity was highest in the right posterior quadrant, lowest in the left anterior quadrant, about equal in the left posterior and right anterior quadrants, and substantially higher in the right half of the nucleus.

The correlation of increasing age with declining cell density was much stronger for the nucleus than for the annulus.

Nucleus cellularity continued to decline throughout life whereas the annulus ceased its decline after the age of 50.

Cell density was low in the vicinity of tears but elsewhere the disc was unaffected.

Extensive inferior and superior end-plate separations reduced cellularity throughout the disc.

Increased thickness of the cartilage end-plate was associated with higher cellularity in the nucleus.

Discussion: The findings that cell density is higher in the posterior annulus and in the right half of the disc, tends to be increased if the cartilage end-plate is thicker, and is not uniformly diminished by large tears, indicates that disc cellularity is influenced by a complex interplay of factors which needs to be understood before attempts are made to restore the structural and functional integrity of degenerate discs.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_III | Pages 438 - 438
1 Sep 2009
Wilby M Vernon-Roberts B Fraser R Moore R
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Introduction: Thickened ligamentum flavum (LF) is a major contributor to the clinical syndrome of lumbar canal stenosis (LCS). The patho-mechanisms responsible for this phenomenon remain unclear. Cysts adjacent to facet joints (FJ) in the spine are regarded as rare entities that may uncommonly contribute to LCS. Inaccurate pathological interpretation and unawareness of a key anatomical feature has generated erratic terminology and confusion about their origin.

Methods: Twenty-seven consecutive patients with radiologically confirmed central canal or lateral recess stenosis underwent lumbar laminectomy for neurogenic symptoms. Surgical specimens comprising en bloc excision of LF and medial inferior facet (to retain LF and FJ relationships) were examined microscopically following staining with haematoxylin-eosin and Miller’s elastic stain. Controls were facet/LF specimens from 89 cadaver lumbar spines.

Results: Mean LF thickness was 8.9 mm (+/− 0.3 mm SEM) at the operated levels and 2.9 mm (+/− 0.3 mm) at the non-operated, adjacent levels (p < 0.01). Twenty-eight synovial cysts (8 bilateral, 12 unilateral) were present at a single level in 20 (74%) patients. Synovial cysts per spine level were: L1/2 = 0; L2/3 = 3; L3/4 = 7; L4/5 = 16; L5/S1 = 2. The cyst levels all showed advanced osteoarthritis and LF degeneration. Ten patients (50 %) with cysts had pre-existing degenerative spondylolisthesis (DS). Only 5 patients had pre-operative radiological apperances of unilateral facet cysts. Therefore 82 % of our observed synovial cysts were microscopic or occult. The synovial cysts communicated with the FJ via a bursa-like cleft within the LF, and their linings of synoviocytes and other cells contained fragments shed from the articular surface. The control cadaver specimens revealed that a synovial bursa or intra-ligamentous out-pouching from the synovial cavity was present in 90% of normal LF at L4/5 and was up to 12 mm in length. This intra-ligamentous synovial recess, either wholly or partially lined by synoviocytes, was only present in 55% of specimens at L1/2 with a maximum length of 5 mm. Several other juxtafacet cyst types were observed in the experimental group and a novel classification based upon pathological findings is presented.

Discussion: Para-facetal intraspinal cysts are common in degenerative lumbar spinal stenosis. DS is also a frequent finding but is statistically unrelated to cyst formation (Chi-square: p=0.187). We have found that debris from osteoarthritic facet joints enters a bursa-like cleft within the LF where it becomes incorporated into the wall where it excites a granulomatous reaction leading to blockage and synovial cyst formation. The existence of this channel has not been reported previously. We suggest that microscopic synovial cysts contribute significantly to the ligamentous thickening seen in LCS. We also present a novel classification of juxtafacet cysts based on our pathological findings.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_III | Pages 429 - 429
1 Sep 2009
Chia C Fagan A Fraser R Hall D
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Introduction: Epidural steroid injection is commonly used for treatment of sciatica. Traditionally these have been administered through a needle inserted in the posterior mid line via an interlaminar (IL) route. However, in recent years the transforaminal (TF) route of administration has become popular. Potential advantages of the TF route include greater accuracy of injection (with radiological confirmation) and placement of the needle tip closer to the point at which the nerve is compressed.

Methods: Consecutive patients from the practices of 2 surgeons that use an IL technique were compared with those from the practices of 2 other surgeons that use a TF technique. Inclusion criteria were leg pain accompanied by a radiological diagnosis of nerve root compression. Both patients with disc prolapse and spinal stenosis were included. Treatment outcome was measured using the Roland-Morris (RM) Score, the Sciatica Frequency and Bothersome Index (SFBI) and the Euroqol (EQ-5D) questionnaire obtained at recruitment and three months after the epidural steroid injection. A global assessment (GA) of outcome; where patients were asked whether they were

much better,

better,

un changed or

worse after treatment; was obtained at 3 months.

Patients were also asked the duration of any relief obtained. Statistical methods utilized included the two tailed t-test, the Wilcoxon Rank Sum test, Odds ratio (OR) and the Chi Squared Test.

Results: 39 patients received an interlaminar epidural steroid injection and 25 received a transforaminal epidural steroid injection (total 64 patients). Follow-up was achieved for 36/39 (92.3%) and 25 (100%) patients respectively. The median pre-test RM score was 11 (range 3–11) for both groups. Post test RM score was 12(6–16) for the IL group and 3 (6–10.5) for the TF group (p=0.01). Median pre-test SFBI was 25 (0–46) and 26 (4–46) for the IL and TF groups respectively. Post test SFBI was 22 (0–46) and 18 (0–41) for the IL and TF groups respectively (p=0.003). Median pre- test EQ-5D was 0.54 for both groups (range 0.06–0.72 for the IL group and 0.08–0.72 for the TF group). Post test EQ-5D was 0.55 (0.06–1) for the IL group and 0.66 (0.06–1) (p=0.21). According to their GA, 11.1% felt much better, 33.3% felt better and 55.6% felt unchanged at 3 months in the IL group. 64% felt much better, 34% better and 12% felt unchanged in the transforaminal group. The proportion of patients having relief for 3 months or more after the injections was 3/36 (8.3%) for the IL group and 10/25 (40%) for the TF group. The transforaminal injection was 7 times more likely to result in pain relief at 3 months. (OR 7.3 95% CI 1.5 – 45.8, p=0.003).

Discussion: Epidural steroid injection by the transforaminal route is more effective then by the interlaminar route in the short term relief of sciatica.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_III | Pages 438 - 438
1 Sep 2009
Ardern D Callary S Wilby M Christensen B Vernon-Roberts B Fraser R Moore R
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Introduction: Spondylolysis in skeletally immature individuals is common but only a small proportion of cases develop pain and spondylolisthesis. The pattern of instability and pathologic consequences of surgically created spondylolytic defects have not previously been described. An animal model of lumbar spondylolysis was created using skeletally immature sheep with the aim of observing the intervertebral mobility and pathologic consequences of creating a spondylolytic segment.

Methods: Bilateral spondylolytic defects were created in the fifth lumbar vertebrae of fourteen sheep aged approximately 16 weeks using a posterior surgical approach. Using tantalum markers that were placed in the lumbar spine segments in the vicinity of the lesion, three dimensional translations and rotations in flexion and extension were recorded under general anaesthetic using Radiostereometric Analysis (RSA) at the time of surgery. A novel method of ovine spine manipulation was developed. Briefly, with the animal in a lateral decubitus position spinal extension was achieved by fixing the shoulders and hips in full extension. Similarly, the limbs were brought into apposition to achieve spinal flexion. A control group of seven sheep had tantalum markers only in the same lumbar spine segments. The animals were re-tested under general anaesthetic at six weeks and six months following surgery. After six months the animals were sacrificed and their spines examined using CT and microscopic analysis.

Results: Bilateral spondylolytic defects did not result in significant transverse (x-axis) translation. RSA showed significant differences between the spondylolytic group (mean 1.22°, range 0.30–3.74) and controls (mean 0.28°, range 0.03–0.77)) for rotation in the axial plane (y-axis, p< 0.0025) immediately after surgery. The spines radiologically stabilised over six months.

Discussion: Surgically induced bilateral spondylolytic defects in this immature ovine model result in increased rotation in the axial plane but do not create transverse translation (spondylolisthesis).


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 363 - 363
1 Oct 2006
Freeman B Fraser R Cain C Hall D
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Introduction: Intra-Discal Electrothermal Therapy (IDET) has been proposed as a treatment for chronic discogenic low back pain. Reports from prospective outcome studies demonstrate statistically significant improvements, but there are no published randomized controlled trials assessing efficacy against a placebo group.

Methods: Ethical committee approval was obtained prior to the study. Patients with chronic low back pain who failed conservative treatment were considered for the study. Inclusion criteria included one or two level symptomatic internal disc disruption as determined by provocative CT/discography. Patients were excluded if there was > 50% loss of disc height or had had previous back surgery. Fifty-seven patients were randomized with a 2:1 (IDET: Placebo) ratio, 38 to the active IDET arm and 19 to the sham (placebo). The IDET catheter was positioned under sedation to cover at least 75% of the annular tear as defined by the CT/discogram. An independent technician connected the catheter to the generator and either delivered electrothermal energy (active group) or did not (sham group). Surgeon, patient and independent outcome assessor were all blinded. All patients followed a standard rehabilitation programme.

Outcome Measures: Low Back Outcome Score (LBOS), Oswestry Disability Index (ODI), SF-36 questionnaire, Zung Depression Index (ZDI) and Modified Somatic Perceptions Questionnaire (MSPQ) were measured at baseline and 6 months. Successful outcome was defined as: No neurological deficit resulting from the procedure, improvement > 7 points in LBOS, improvements > 7 points in SF-36 subsets (pain / disability, physical functioning and bodily pain)

Results: Two subjects withdrew from the study (both IDET). Baseline demographic data, employment and worker’s compensation status, sitting tolerance, initial LBOS, ODI, SF-36, ZDI and MSPQ were similar for both groups. No neurological deficits occurred as a result of either procedure. No subject in either treatment arm showed improvement of > 7 points in LBOS or the specified domains of the SF-36. Mean ODI was 41.4 at baseline and 39.7 at 6 months for the IDET group compared to 40.7 at baseline and 41.5 at six months for the Placebo group. There was no significant change in ZDI or MSPQ scores for either group.

Discussion: No subject in either treatment arm met criteria for successful outcome. There was no significant change in outcome measures in either group at six months. This study demonstrates no significant benefit from IDET over placebo.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 458 - 458
1 Oct 2006
Fagan A Fraser R McKenzie I Balaji V Ryan W
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Introduction This is a Prospective Comparative cohort study to determine the change in the Low Back Outcomes Score (LBOS) after intensive non-operative, multi-disciplinary treatment for low back pain and to compare this with data collected from earlier cohorts undergoing surgical fusion. Recently published Randomised Controlled Trials have been inconclusive regarding the benefits of surgery compared with rehabilitation for low back pain. We examine this question using the Low Back Outcome Score (LBOS) as an outcome measure.

Methods The LBOS was acquired prior to and two years following treatment in cohorts undergoing fusion or rehabilitation for low back pain. Follow up was 70% and 90% respectively. The surgical group had a lower starting LBOS ( 18 v 27) but the rehabilitation group had a higher proportion of cases involved in compensation, litigation, and who were not working.

Results A significantly greater improvement in LBOS was seen in the surgically treated group than was seen in the rehabilitation group (18 v 10)

Discussion Although we do not propose surgery before non-operative treatments are exhausted, these results suggest that surgical treatment can have significant benefits for selected patients who have not improved despite a state of the art rehabilitation programme.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 452 - 453
1 Oct 2006
Fraser R Serhan H Voronov L Tzermiadianos M Carandang G Heavy R Patwardhan A
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Introduction The unacceptably low fusion rate with stand-alone ALIF cages led to the practice of combining ALIF with posterior instrumentation. Recently ALIF combined with anterior lumbar plate fixation has been promoted to obviate the need for additional posterior surgery. The purpose of this study is to compare the multidirectional flexibility of ALIF combined with posterior instrumentation (either translaminar facet screws or pedicle screws) to that combined with anterior plate fixation.

Methods Ten human lumbar cadaveric motion segments were tested in the following sequence: (i) intact, (ii) stand alone ALIF cages, (iii) ALIF and anterior lumbar plate, (iv) ALIF with translaminar facet screws, (v) ALIF with pedicle screws. In each condition, the specimens were tested under bending moments of 0–8 Nm flexion, 0–6 Nm extension, 0–6 Nm lateral bending and 0–5 Nm axial rotation. 3D motions were measured using an optoelectronic motion monitoring system.

Results The ALIF cages decreased the ROM in the sagittal and frontal planes (p< 0.05). Their effectiveness improved in the sagittal plane with the combination of either anterior plate or posterior fixation (p< 0.05). There was no statistical difference between the ALIF/ Plate and translaminar screws or pedicle screws in flexion-extension and axial rotation ROM. There was a difference in the lateral bending ROM between the ALIF with anterior plate and ALIF with either translaminar facet screws or ALIF with pedicle screws (p< 0.05) favouring posterior fixation. However there was no statistical difference between the combined ROM for ALIF/Plate and translaminar screws or pedicle screws.

Discussion This study shows that the stability achieved with the combination of ALIF with an anterior plate is comparable to that achieved with posterior instrumentation with translaminar facet screws or pedicle screws. This suggests that sufficient segmental stability may be provided by anterior plating, obviating the need for a concomitant posterior approach.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 408 - 408
1 Sep 2005
Walters R Moore R Fraser R
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Introduction Infection is a risk following surgical procedures that violate the disc. Bacteria, often from normal skin flora, can be introduced into the disc space causing inflammation with destruction of the adjacent vertebrae. The incidence of iatrogenic discitis is thought to be reduced with the use of prophylactic antibiotics. Although there is substantial evidence from animal studies that prophylactic antibiotics reduce the incidence of discitis, evidence in humans is not strong. The aim of this study was to determine if levels of cephazolin in human disc and serum reached the stated minimum inhibitory concentration (MIC > 1 mg/L) against Staphylococcus aureus following intravenous administration.

Methods Thirty patients (15 female and 15 male) with a mean age 42 years, (range 21–63 years) received 1g cephazolin prior to one or two level lumbar spinal fusion surgery. Venous blood was collected prior to intravenous administration of cephazolin and again at the time of disc removal to measure its concentration in serum and disc tissue.

Results The interval between cephazolin administration and tissue sampling ranged from 7 to 137 minutes. Cephazolin concentration in the serum (31.1 – 148 mg/L) was greater than in the disc (0 – 9.5 mg/L). The concentration of cephazolin peaked in the serum at 7 minutes and in the disc between 37 and 53 minutes. Over 70% of the disc samples had detectable levels of cephazolin at the time the disc was removed, although only half had cephazolin levels above 1 mg/L.

Discussion For a given time period the antibiotic concentration in the disc varies between patients. Only one measurement was taken from the disc using the method described when in fact if multiple measurements were taken over time there may be an antibiotic concentration peak in the disc followed by a steady decline. Variability between peak antibiotic concentration in the disc may be attributed to patient size, weight, gender, co-morbidities (diabetes, rheumatoid arthritis) and degree of disc degeneration. However the most critical variable for all patients is timing of administration of antibiotic to achieve optimal concentration in the disc when it is at greatest risk of inadvertent inoculation.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 399 - 399
1 Sep 2005
Moore R Burke J Anjarwalla N Rhamat R Brown G Taylor D Fraser R
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Introduction Magnetic resonance imaging (MRI) is a valid investigation for the diagnosis of intervertebral disc disease, including infection, but it is expensive and difficult to access conveniently for research studies on live animals under anaesthesia. The aim of this study was to compare the MRI signal changes in spines from living and recently deceased sheep.

Methods MRI was conducted on the lumbar spines of six adult sheep from research studies investigating bacterial discitis, chemical discitis and disc degeneration resulting from annular incision. The sheep was anaesthetised and the lumbar spines were imaged with a Siemens Magneton Vision MRI (Numaris VB33G software) using T1 SGE, T1 FSE, STIR and T2 FSE sequences. The sheep were killed with an intravenous overdose of barbiturate and identical images were obtained commencing five minutes post mortem.

Results For each of the disease processes under consideration the MRI contrast relationships were maintained between all of the anatomical structures of interest. The post-mortem images provided improved clarity, particularly in the STIR and T2-weighted sequences, due to the absence of pulsation from the CSF and aorta, as well as the absence of respiratory artefact.

Discussion The MRI appearances of spinal tissues following death correlate well with those in the live animal confirming the validity of this method of investigation. This is particularly relevant for optimisation of a busy clinical resource for research purposes.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 221 - 221
1 Sep 2005
Freeman B Walters R Moore R Fraser R
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Objective: To investigate the effects of intra-discal electro-thermal therapy (IDET) on an experimentally induced posterolateral annular inter vertebral disclesion in sheep.

Summary of Background Data: IDET is being used increasingly as a minimally-invasive treatment for chronic discogenic low back pain, with success reported in up to 70% of cases. The mechanism of action however is poorly understood. Proposed mechanisms include the contraction of collagen and the coagulation of annular nociceptors. An ovine model was used to assess the innervation of peripheral posterolateral annular lesions and the potential for IDET to denervate this region.

Methods: Posterolateral annular incisions were made in 36 lumbar discs of 18 sheep. After twelve weeks the sheep underwent IDET at one level and a sham treatment at the other level. IDET was performed using a modified intradiscal catheter (SpineCATH™, Oratec Interventions Inc., Menlo Park, CA). Temperatures were recorded in the nucleus (TN) and the posterior annulus (TPa). The spines were harvested at intervals up to eighteen months. Histological sections of the discs were stained with haematoxylin and eosin and an antibody to the general neuronal marker PGP 9.5.

Results: The target temperature of 90°C at the catheter was tip was reached in all cases. The mean maximum TPa was 63.6°C and the mean maximum TN 67.8°C. Vascular granulation tissue consistent with a healing response was observed in the region of the posterior annulus tear of all incised discs from 12 weeks. PGP 9.5 positive nerve fibres were clearly identified in the adjacent periannular tissue, but were scarce within the outer few lamellae of the annulus. There were no fewer nerve fibres identified in those specimens that had undergone IDET. From six weeks after IDET there was evidence of thermal necrosis in the inner annulus, sparing the periphery of the disc.

Conclusions: IDET delivered at 90°C in the sheep consistently heats the posterior annulus and the nucleus to a temperature range associated with coagulation of nociceptors and collagen contraction. Thermal necrosis was observed within the inner annulus from six weeks after IDET. In this model IDET did not produce denervation of the experimentally induced posterior annular lesion.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_IV | Pages 459 - 460
1 Apr 2004
Fraser R Ross E Lowery G Freeman B Dolan M
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Introduction: The purpose of this study was to evaluate the design of a titanium/polyolefin artificial disc, assess its safety and measure outcome to determine if a RCT is justified.

Methods: All subjects entered this pilot study with one or two-level disc disruption at l4/l5 and/or l5/s1 and had disabling low back pain for at least 12 months. The diagnosis was confirmed by discography. Independent assessment included physical examination, VAS for pain, Low-Back Outcome Score (LBOS), Oswestry Disability Index (ODI), SF-36, lateral flexion/extension radiographs and MRI. This was carried out preoperatively, at 6 and 12 weeks, 6 months and at 1 and 2 years. Surgery was performed by an anterior retroperitoneal approach.

Results: Twenty-eight cases (14 males; average 41 years) were operated on during 1998–2000. Surgery was performed at L5/S1 in 19, L4/L5 in 5 and both levels in 4. Operating time averaged 130 minutes with 180mls average blood loss. There were no operative complications and average length of stay was 6 days. At 2 years there was 39% average improvement in vas, 15-point average improvement in ODI, 14 point average improvement in LBOS and improvement in 5 of the 8 SF-36 sub-scales. Complications included detection by plain radiographs of early partial displacement of implant in one case and late heterotopic calcification in another. Thin section helical CT, first carried out in early 2001, revealed polyolefin tears in 10 patients, four undergoing revision surgery since 2-year follow-up. CT revealed instances of osteolysis associated with polyolefin failure and hetero-topic bone formation not seen on plain radiographs.

Discussion: Although improvements in clinical outcome comparable to that reported with fusion were obtained at two years, detection of elastomer tears by thin section CT in 36% of patients indicated the prosthesis was not suitable for clinical use. This finding was unexpected given the results of prior extensive mechanical testing1.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_IV | Pages 491 - 491
1 Apr 2004
Wai E Santos E Fraser R
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Introduction Numerous in-vitro studies demonstrating increased stress at levels adjacent to a lumbar fusion have raised concerns of accelerated degeneration. However, the significance of this increased stress in the in-vivo setting remains unclear, especially with long-term follow-up. The objective of this study was to assess the level of degeneration on MRI in this same cohort of patients at a minimum of 20 years follow-up.

Methods Thirty-seven patients undergoing lower lumbar anterior lumbar interbody fusion with a minimum of 20 years follow-up were identified. Only patients with normal pre-operative discograms at the level adjacent to the fusion were considered in this study. MRI scans were performed and evaluated for any evidence of degeneration by an independent radiologist. Advanced degeneration was defined as either: (1) absence of T2 signal intensity in the disk, (2) disk herniation, or (3) spinal canal stenosis.

Results Advanced degeneration was identified in eight (22%) patients, with five (14%) being isolated to the adjacent level. Nineteen (51%) other patients had evidence of early degeneration in their lumbar spine. Overall, 10 (26%) patients had some evidence of degeneration isolated to the level adjacent to the disk whereas 17 (31%) patients had multilevel degeneration and six patients (16%) had degeneration in their lumbar spine but preservation of the adjacent level. There was no relationship between function and radiographic degeneration.

Conclusions Without a control group, it is difficult to make firm conclusions on whether the changes seen on MRI represent the natural history of spinal deterioration or represent accelerated degeneration. However, after 20 years, only a handful of patients developed advanced adjacent level degeneration. Furthermore, the majority of degenerative changes seen occurred over multiple levels or at levels not adjacent to the fusion, suggesting that changes seen may be more likely related to constitutional factors inherent within the individual as opposed to the increased biomechanical stresses at the adjacent levels.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_IV | Pages 461 - 462
1 Apr 2004
Rahmat R Matsacos D Oakes B Fraser R Moore R
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Introduction: Disc degeneration is consistent with advancing age and in many cases is associated with back pain and restricted mobility. The traditional surgical treatment for chronic back pain has been spinal fusion to immobilize the painful level. Long-term studies, however, suggest that fusion actually promotes degeneration at adjacent levels. One of the hallmarks of disc degeneration is aggregation of chondrocytes in the nucleus of chondrones, and more recently apoptosis has been implicated as a factor controlling the longevity of the cells. Recent research suggests that it may be possible to restore normal function to degenerate discs by introducing a fresh population of cells. This study investigated the potential for autologous costal chondrocyte implantation to prevent lumbar disc degeneration after annular injury in the sheep.

Methods: the lumbar spines of eight adult sheep were exposed. In four animals, full thickness annular incisions were made in three alternate discs. No annular incisions were made in the other four sheep. A minimum of 500 mg of cartilaginous tissue was harvested from the twelfth rib of all animals. Tissue was cultured in vitro and the chondrocytes were labelled with a fluorescent marker for retrospective identification. After six weeks the chondrocytes were injected into the lower two alternate discs of all animals, leaving the uppermost discs and those untouched as internal controls. The animals were killed at intervals from three to twenty-four weeks and MRI, plain x-ray, histology and immunocytochemistry were evaluated.

Results: MRI at twelve and twenty-four weeks showed apparent preservation of all incised discs that had been transplanted with autologous chondrocytes. Histology revealed clusters of viable chondrocytes of normal appearance within the nucleus. These cells stained positive for the fluorescent label. The same cells and the surrounding matrix were also positive for collagen type II. Serial X-ray measurements suggested that progressive disc degeneration was arrested in the discs that received autologous costal chondrocytes.

Discussion: This pilot study showed evidence that cultured autologous costal chondrocytes remained viable and produced extracellular matrix following transplantation into normal and degenerate discs. In contrast to other studies that have used mesenchymal stem cells or chondrocytes harvested directly from discs, this study demonstrated success with cells from a source other than the disc. Costal cartilage is a convenient source of cells for transplantation and this technique warrants further investigation as a potential treatment for degenerative disc disease.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_IV | Pages 462 - 462
1 Apr 2004
Walters R Moore R Rahmat R Shimamura Y Fraser R
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Introduction: Although prophylactic antibiotic administration is common in spinal surgery, the choice of drug, dose, and timing of administration often varies. Little is known about the activity of antibiotics in the spine and indeed if they are distributed throughout the disc and if the time intervals are optimal. Because infections that produce iatrogenic discitis generally arise within the disc, the antibiotic concentration of the disc is more relevant than serum concentrations. The aims of the study were to determine if a 2g dose of cephazolin was effective at preventing discitis over a four-hour period in immature ovine discs that were both non-degenerate and degenerate; and also to determine the concentration of cephazolin in serum and disc tissue.

Methods: In 10 Merino wethers aged 12 weeks, three lumbar discs were “degenerated” by incising the posterolateral annulus with a scalpel blade and using ronguers, removing the bulk of the nucleus pulposus. After 12 weeks nine animals were anaesthetised and given a 2g dose of cephazolin (David Bull Laboratories, Australia) at predetermined time intervals over a four-hour period. The antibiotic was chosen for effectiveness against Staphylococcus aureus a common discitis-causing organism. One sheep (control) did not receive any antibiotics to follow the natural progression of infection. All animals had discography with radiographic contrast that contained S. aureus at two incised levels and at two non-incised levels. Lateral radiographs of the lumbar spine were taken at two, six and 12 weeks to monitor the bony changes. At 12 weeks all sheep were given a 2g intravenous dose of cephazolin at time intervals before being killed. The spines were removed and prepared for light microscopy to assess pathology of the discs and for biochemical analysis of antibiotic concentration. Success of treatment was judged using histologic and radiographic features.

Results: The control sheep that did not receive any antibiotics developed discitis at four levels. Histology at 12 weeks confirmed discitis in 10/36 “prophylactic discs”. Of these “prophylactic discs” 7/10 had previously been “degenerated”. Discitis only developed in immature discs that were administered cephazolin two hours prior to inoculation. When antibiotic was administered after inoculation discitis was prevented. Biochemistry results confirmed that antibiotic diffused throughout the disc but was concentrated in the annulus more than the nucleus. Antibiotic levels in the disc peaked at 15 minutes (annulus mean concentration 15.5 mg/L, nucleus mean concentration 3.2 mg/L). Serum levels at 15 minutes were up to 50 times greater at this time (serum mean concentration 178 mg/L).

Discussion: The discs that were “degenerate” had a higher incidence of discitis compared to “non-degenerate” discs. However the concentration of antibiotic in degenerate discs was not significantly different than in non-degenerate discs. A 2 gram dose of cephazolin is reasonably effective (approx 70% success rate) at preventing discitis over a four-hour period.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_IV | Pages 484 - 485
1 Apr 2004
Freeman B Fraser R Cain C Hall D
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Introduction Intra-Discal Electrothermal Therapy (IDET) has been proposed as a treatment for chronic discogenic low back pain. Reports from prospective outcome studies demonstrate statistically significant improvements, but to date there are no published randomized controlled trials assessing efficacy versus a placebo group.

Methods Ethical committee approval was obtained prior to the study. Patients with chronic low back pain who failed to improve with conservative therapy were considered. Inclusion criteria included the presence of one or two level symptomatic disc degeneration with posterior or postero-lateral annular tears as determined by provocative CT/discography. Patients were excluded if there was > 50% loss of disc height or previous back surgery. Fifty-seven patients were randomized with a 2:1 (IDET: Placebo) ratio, 38 to the active IDET arm and 19 to the sham procedure (placebo). In all cases the IDET catheter was positioned under sedation to cover at least 70% of the annular tear defined by the CT/discogram. An independent technician connected the catheter to the generator and either delivered electrothermal energy (active group) or did not (sham group). Both surgeon and patients were blinded to the treatment. Patients followed a standard post-procedural rehabilitation programme. Low Back Outcome Score (LBOS), Oswestry Disability Index (ODI), SF-36 questionnaire, Zung Depression Index (ZDI) and Modified Somatic Perceptions Questionnaire (MSPQ) were measured at baseline and six months. Successful outcome was defined as: no neurological deficit resulting from the procedure, improvement in LBOS of > 7 points, improvements in SF-36 subsets (pain/disability, physical functioning and bodily pain). Two subjects withdrew from the study (both IDET). Baseline demographic data, employment and workers’ compensation status, sitting tolerance, initial LBOS, ODI, SF-36, ZDI and MSPQ were similar for both groups.

Results No neurological deficits occurred as a result of either procedure. No subject in either treatment arm showed improvement of > 7 points in LBOS or specified domains of the SF-36. Mean ODI was 41.4 at baseline and 39.7 at six months for the IDET group compared to 40.7 at baseline and 41.5 at six months for the placebo group. There was no significant change in ZDI or MSPQ scores for either group. No subject in either treatment arm met criteria for successful outcome. Further analysis showed no significant change in outcome measures in either group at six months.

Conclusions This study demonstrates no significant benefit from IDET over placebo.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_I | Pages 95 - 95
1 Jan 2004
Walters R Rahmat R Moore R Fraser R
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Introduction: Infection can occur after any spinal procedure that involves entry into the disc and although it is not common, the potential consequences are serious. Treatment usually requires identification of the bacteria followed by a course of antibiotics. This treatment remains controversial since it is not clear whether antibiotics actually penetrate the disc and if so, whether they are effective, or even if the outcome would be the same without antibiotics.

For an antibiotic to be effective against the infecting organism it must diffuse through the disc matrix. Blood vessels that surround the disc facilitate the diffusion process, but with age this vascularity decreases and may impede diffusion.

The aims of the pilot study were to assess the effectiveness of antibiotic in treating infection in both normal and degenerate sheep discs and to measure the concentration of antibiotic in non-operated discs at varying ages.

Methods: In each of six Merino wethers aged 12 weeks (n=3) and 24 months (n=3), two lumbar discs were “degenerated” by incising the posterolateral annulus with a scalpel blade. After four weeks all animals had discography with radiographic contrast that contained Staphylococcus aureus at the incised levels and at two non-incised levels. Seven days after infection four animals began IV antibiotic treatment with cephazolin sodium (David Bull Laboratories, Australia) for 21 days at a dose of 50mg/kg/day. The antibiotic was chosen for effectiveness against S. aureus. One control animal from each age group did not receive any antibiotics, to follow the natural progression of infection. Lateral radiographs of the lumbar spine were taken at two, six and 12 weeks. At 12 weeks all sheep were given a single intravenous dose of cephazolin sodium as either a 1, 2 or 3g dose. The sheep were then killed after 30 minutes. The spines were removed and prepared for light microscopy to assess pathology of the discs and for biochemical analysis of antibiotic concentration. Success of treatment was judged using histologic and radiographic features.

Results: Discitis was evident radilogically as early as two weeks after inoculation in all animals. Histology at 12 weeks confirmed discitis in all discs regardless of treatment. Biochemistry results confirmed that antibiotic diffused throughout the disc but was more concentrated in the annulus than the nucleus. At all doses disc concentration of antibiotic was higher in lambs than sheep.

Discussion: Treatment with cephazolin sodium at a dose of 50mg/kg/day for 21 days administered from seven days after inoculation, did not prevent discitis. This does not appear to be due to inability of antibiotic diffusion into the disc.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_I | Pages 89 - 89
1 Jan 2004
Wai E Santos E Fraser R
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Introduction: Numerous in-vitro studies demonstrating increased stress at levels adjacent to a lumbar fusion have raised concerns of accelerated degeneration. However, the significance of this increased stress in the in-vivo setting remains unclear, especially with long-term follow-up. The objective of this study is to assess the level of degeneration on MRI in this same cohort of patients at a minimum of twenty years follow-up.

Methods: Twenty-five patients undergoing one or two level anterior lumbar interbody fusion at the L5-S1 or L4–5 levels with a minimum of twenty-years follow-up were identified. Only patients with normal preoperative discograms at the level adjacent to the fusion were considered in this study. MRI scans were performed and evaluated for any evidence of degeneration by an independent radiologist. Advanced degeneration was defined as either: (1) absence of T2 signal intensity in the disk, (2) disk herniation, or (3) spinal canal stenosis.

Results: Advanced degeneration was identified in five (20%) patients, with three (12%) being isolated to the adjacent level. Fourteen (56%) other patients had evidence of early degeneration in their lumbar spine. Overall, eight (32%) patients had some evidence of degeneration isolated to the level adjacent to the disk whereas seven (28%) patients had multilevel degeneration and four patients (16%) had degeneration in their lumbar spine but preservation of the adjacent level.

Discussion & Conclusion: Without a control group, it is difficult to make firm conclusions on whether the changes seen on MRI represent the natural history of spinal deterioration or represent accelerated degeneration. However, after twenty-years, only a handful of patients developed advanced adjacent level degeneration. Furthermore, the majority of degenerative changes seen occurred over multiple levels or at levels not adjacent to the fusion, suggesting that changes seen may be more likely related to constitutional factors inherent within the individual as opposed to the increased biomechanical stresses at the adjacent levels.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_I | Pages 84 - 85
1 Jan 2004
Fagan A Moore R Roberts BV Blumbergs P Fraser R
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Introduction: Although it is well recognized that the outer annulus is innervated, the relative densities of innervation of different regions of the disc have not been quantitated. We present here the first comparative analysis of the innervation of the innervation of different regions of the lumbar intervertebral disc.

Methods: A sheep model was used allowing evaluation of the whole motion segment. Four sheep spines were used. One was processed for PGP 9.5 immunoflourescence and three were processed for PGP 9.5 immunoperoxidase histochemistry. Serial sagittal sections were obtained and a count was made of the densities of innervation of different regions of the endplate and annulus. These were compared to identify which areas of the disc and endplate are most innervated.

Results: The endplate innervation is concentrated centrally adjoining the nucleus. The mean density of innervation of the central endplate was 0.44 (SEM 0.07) nerves/ mm2 while the mean density of the peripheral endplate was 0.10 (SEM 0.03) nerves/ mm2 (p= 0.0001). There was no significant difference between the overall endplate and annulus innervation densities 0.52 (SEM 0.1) v 0.37 (SEM 0.07) p=0.2. But the peri-annular connective tissue, external to the outer annulus contained the densest innervation of any region in the motion segment 1.05 (SEM 0.16).

Discussion: The lumbar intervertebral disc has a meagre innervation. This is concentrated in the peri-annular connective tissue and the central endplate. While receptor threshold is more closely related to nociceptive function than innervation density, these findings have important implications for any treatment of discogenic pain.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_I | Pages 85 - 85
1 Jan 2004
Freeman B Walters R Moore R Vernon-Roberts B Fraser R
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Introduction: Intradiscal electrothermal therapy (IDET) is being used increasingly as a minimally-invasive treatment for chronic discogenic low back pain, with success reported in up to 70% of cases. The mechanism of action however is poorly understood. Proposed mechanisms include the contraction of collagen and the coagulation of annular nociceptors. An ovine model was used to assess the innervation of peripheral posterolateral annular lesions and the potential for IDET to denervate this region.

Methods: Posterolateral annular incisions were made in 36 lumbar discs of 18 sheep. After twelve weeks the sheep underwent IDET at one level and a sham treatment at the other level. IDET was performed using a modified intradiscal catheter (SpineCATH™, Oratec Interventions Inc., Menlo Park, CA). Temperatures were recorded in the nucleus and the posterior annulus. The spines were harvested at intervals of up to eighteen months. Histological sections of the discs were stained with haematoxylin and eosin and an antibody to the general neuronal marker PGP 9.5.

Results: The target temperature of 90°C at the catheter tip was reached in all cases. The mean maximum TPa was 63.6°C and the mean maximum TN was 67.8°C. Vascular granulation tissue consistent with a healing response was observed in the region of the posterior annulus tear of all incised discs from 12 weeks. PGP 9.5 positive nerve fibres were clearly identified in the adjacent periannular tissue, but were scarce within the outer few lamellae of the annulus. There were no fewer nerve fibres identified in those specimens that had undergone IDET. From six weeks after IDET there was evidence of thermal necrosis in the inner annulus, sparing the periphery of the disc.

Discussion: IDET delivered at 90°C in the sheep consistently heats the posterior annulus and the nucleus to a temperature associated with coagulation of nociceptors and collagen contraction. Thermal necrosis was observed within the inner annulus from six weeks after IDET. In this model IDET did not appear to produce denervation of the posterior annular lesion.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_III | Pages 284 - 285
1 Mar 2003
Wai E Santos E Fraser R
Full Access

INTRODUCTION: Numerous in-vitro studies demonstrating increased stress at levels adjacent to a lumbar fusion have raised concerns of accelerated degeneration. However, the significance of this increased stress in the in-vivo setting remains unclear, especially with long-term follow-up. The objective of this study is to assess the level of degeneration on MRI in this same cohort of patients at a minimum of twenty years follow-up.

METHODS: Twenty-five patients undergoing one or two level anterior lumbar interbody fusion at the L5-S1 or L4-5 levels with a minimum of twenty-years follow-up were identified. Only patients with normal pre-operative discograms at the level adjacent to the fusion were considered in this study. MRI scans were performed and evaluated for any evidence of degeneration by an independent radiologist. Advanced degeneration was defined as either: (1) absence of T2 signal intensity in the disk, (2) disk herniation, or (3) spinal canal stenosis. RESULTS: Advanced degeneration was identified in five (20%) patients, with three (12%) being isolated to the adjacent level. Fourteen (56%) other patients had evidence of early degeneration in their lumbar spine. Overall, eight (32%) patients had some evidence of degeneration isolated to the level adjacent to the disk whereas seven (28%) patients had multilevel degeneration and four patients (16%) had degeneration in their lumbar spine but preservation of the adjacent level.

DISCUSSION AND CONCLUSION: Without a control group, it is difficult to make firm conclusions on whether the changes seen on MRI represent the natural history of spinal deterioration or represent accelerated degeneration. However, after twenty years, only a handful of patients developed advanced adjacent level degeneration. Furthermore, the majority of degenerative changes seen occurred over multiple levels or at levels not adjacent to the fusion, suggesting that changes seen may be more likely related to constitutional factors inherent within the individual as opposed to the increased biomechanical stresses at the adjacent levels.