Aims

The aim of this study was to evaluate the epidemiology and treatment of Perthes’ disease of the hip.

Aims

The aim of this study was to inform the epidemiology and treatment of slipped capital femoral epiphysis (SCFE).

Introduction

There is widespread variation in the management of rare orthopaedic disease, in a large part owing to uncertainty. No individual surgeon or hospital is typically equipped to amass sufficient numbers of cases to draw robust conclusions from the information available to them. The programme of research will establish the British Orthopaedic Surgery Surveillance (BOSS) Study; a nationwide reporting structure for rare disease in orthopaedic surgery.

Aims

Slipped capital femoral epiphysis (SCFE) is one of the most common hip diseases of adolescence that can cause marked disability, yet there is little robust evidence to guide treatment. Fundamental aspects of the disease, such as frequency, are unknown and consequently the desire of clinicians to undertake robust intervention studies is somewhat prohibited by a lack of fundamental knowledge.

Introduction

Wear debris and metal ions originating from metal on metal hip replacements have been widely shown to recruit and activate macrophages. These cells secrete chemokines and pro-inflammatory cytokines that lead to an adverse local tissue reaction (ALTR), frequently requiring early revision. The mechanism for this response is still poorly understood. It is well documented that cobalt gives rise to apoptosis, necrosis and reactive oxygen species generation. Additionally, cobalt stimulates T cell migration, although the effect on macrophage motility remains unknown. This study tests the hypothesis that cobalt ions and nanoparticles affect macrophage migration stimulating an ALTR.

Introduction

Primary cilia are singular structures containing a microtubule-based axoneme which are believed to not only be mechanosensitive but also to co-ordinate many cell functions via signalling pathways including Hedgehog and Wnt. Primary cilia have previously been described on cells of mouse intervertebral discs (IVDs), but not in bovine or human IVDs. Our aim was to examine primary cilia in these species.

Introduction

Primary cilia are organelles found singularly on almost every cell in the body, including tenocytes. Tendon is a hierarchical, composite structure, and previous work from our group has suggested that the cell populations in the inter-fascicular matrix (IFM) may be different from those within the fascicle matrix (FM). This study investigated how stress deprivation influenced the primary cilia of both cell types, and the mechanics of the IFM and the FM.

Introduction: Flexion distraction injuries (FDI)of the thoracic and lumbar spine can be stabilized with a short construct spanning one motion-segment. This fracture is functionally defined by failure of the posterior and middle columns in tension and the anterior column in compression or tension. Treatment of a predominantly bony injury with minimal deformity (Chance type) is usually non-operative. Intra-abdominal pathology, and ligamentous spinal instability are relative indications for surgery. Deformity of greater than 17 degrees of kyphosis has a poor prognosis when treated conservatively, and represents true instability in vitro. Surgical treatment is mainly through a posterior approach with instrumentation. Which construct to use and the number of motion segments to include is controversial. Multi-level instrumentation techniques both in distraction and compression have been used as well as shorter constructs, particularly in the lumbar spine. We addressed the efficacy of single motion-segment fixation by evaluating the radiographic and functional results of this treatment technique.

Methods: All patients diagnosed with a FDI were prospectively identified over a 48 month period. Non-operatively treated fractures were excluded. Other spine fractures were excluded. Demographics, comorbidity, neurological status, operative details and complications were recorded. Radiographic reviewers were blinded to the functional outcome of the patient and the time of follow-up. The Oswestry Functional Assessment Questionnaire was administered by mail.

Results: Twenty-one eligible patients were identified. A significant (p< 0.0001) correction of deformity was achieved, from a mean preoperative kyphosis of 10.1 degrees to a mean postoperative lordosis of 0.9 degrees. No loss of correction occurred. The mean Oswestry score was 11.5, with 88% of patients having minimal disability. One patient died from unrelated morbidity.

Conclusions: Hoshikawa etal showed in vitro how compression forces alone can create FDI. Compression without flexion causes burst fractures. With moderate flexion there is FDI with anterior body compression. With increasing flexion FDI becomes entirely distractive. As the forces are concentrated at a single point, reconstruction only requires that this location be addressed. As all FDI are created by the same mechanism, regardless of structures injured only short segment fixation is required.

We have demonstrated in FDI, single level fixation is biomechanically sound. Multilevel instrumentation creates loss of adjacent level motion segments. This is not necessary. The absence of a control group precludes absolute conclusions. Nonetheless most patients reported minimal disability related to their back and had excellent radiological outcomes. This study demonstrates that posterior reduction and stabilization of a single motion-segment for FDI can adequately stabilize the spine and lead to excellent functional outcomes.

INTRODUCTION: Flexion distraction injuries (FDI) of the thoracic and lumbar spine can be stabilised with a short construct spanning one motion-segment. This fracture is functionally defined by failure of the posterior and middle columns in tension and the anterior column in compression or tension. Treatment of a predominantly bony injury with minimal deformity (Chance type) is usually non-operative. Intra-abdominal pathology, and ligamentous spinal instability are relative indications for surgery. Deformity of greater than 17 degrees of kyphosis has a poor prognosis when treated conservatively, and represents true instability in vitro. Surgical treatment is mainly through a posterior approach with instrumentation. Which construct to use and the number of motion segments to include is controversial. Multi-level instrumentation techniques both in distraction and compression have been used as well as shorter constructs, particularly in the lumbar spine. We addressed the efficacy of single motion-segment fixation by evaluating the radiographic and functional results of this treatment technique.

METHODS: All patients diagnosed with a FDI were prospectively identified over a 48 months period. Non-operatively treated fractures were excluded. Other spine fractures were excluded. Demographics, co-morbidity, neurological status, operative details and complications were recorded. Radiographic reviewers were blinded to the functional outcome of the patient and the time of follow-up. The Oswestry Functional Assessment Questionnaire was administered by mail.

RESULTS: Twenty-one eligible patients were identified. A significant (p< 0.0001) correction of deformity was achieved, from a mean pre-operative kyphosis of 10.1 degrees to a mean post-operative lordosis of 0.9 degrees. No loss of correction occurred. The mean Oswestry score was 11.5, with 88% of patients having minimal disability. One patient died from unrelated morbidity.

CONCLUSIONS: Hoshikawa et al showed in vitro how compression forces alone can create FDI. Compression without flexion causes burst fractures. With moderate flexion there is FDI with anterior body compression. With increasing flexion FDI becomes entirely distractive. As the forces are concentrated at a single point, reconstruction only requires that this location be addressed. As all FDI are created by the same mechanism, regardless of structures injured only short segment fixation is required.

We have demonstrated in FDI, single level fixation is biomechanically sound. Multilevel instrumentation creates loss of adjacent level motion segments. This is not necessary. The absence of a control group precludes absolute conclusions. Nonetheless most patients reported minimal disability related to their back and had excellent radiological outcomes. This study demonstrates that posterior reduction and stabilisation of a single motion-segment for FDI can adequately stabilise the spine and lead to excellent functional outcomes.

Background: Current treatments for Low back pain (LBP) are often empirical and few directed at the underlying disorder, altered discal cell metabolism, which precipitates the problem. The use of gene therapy to manipulate discal metabolism to treat LBP is an interesting possibility. The Intervertebral disc (IVD) is a therapeutic target in LBP, and one approach to gene therapy would be to isolate IVD chondrocytes (IVDC) and transfer genes Ex Vivo into these cells. Subsequent reinjection of these genetically altered cells into the lumbar IVD, would permit the expression of the trans-gene in vivo, generating the therapeutic protein within the IVD.

Methods: To test the viability of this approach, we isolated human IVDC from patients undergoing surgery, grew them Ex vivo and transfected them with the marker gene LacZ, using an adenovirus vector and the CMV promoter. Expression of the gene was then measured using X-gal staining for the gene product ~-galactosidase.

Results: IVDC infected with adenovirus/CMV-LacZ showed maximal LacZ expression 2 days post infection, with almost 50% of cells displaying X-gal positivity within monolayer cultures and 100% infection within alginate culture, gene expression was maintained up to 4 weeks and control cultures showed no LacZ expression.

Conclusion: This study shows that human IVDC can be transfected with a foreign gene using the adenovirus vector. The gene transduction of a therapeutic gene into IVDC, could provide long lasting effect. In addition the use of inducible promoters could allow for the autoregulation of gene expression.

Purpose and Background: We have previously reported our investigations of nerve ingrowth into intervertebral discs (IVD) from patients with mechanical low back pain. We have shown that in discs that are painful on discography (pain level discs) nerves actively grow into the deep annulus fibrosus and nucleus pulposus. Nerve ingrowth accompanies blood vessel ingrowth and advances into the nucleus pulposus from the end plate. The morphology and neurochemistry of these nerves indicate them to be nociceptive.

The growth of non-myelinated pain fibres in other settings is regulated by the cytokine Nerve Growth Factor (NGF). In this study, we have investigated the production and distribution of NGF, or more particularly its active isoform – NGF-β, and its receptors, in diseased intervertebral discs in order to establish whether this cytokine might be responsible for the observed nerve ingrowth in this situation.

Methods: Tissue sections of 21 pain level, 15 non-pain level diseased and 12 normal intervertebral discs, taken at the time of spinal surgery, and from cadavers, were probed by radioactive in situ hybridisation (ISH) for expression of NGF-β, and by immunohistochemistry (IHC) for its high and low affinity receptors (trk-A and p75 respectively). In addition, either serial sections were stained with cell specific markers (CD31 – endothelial cell, PGP9.5 – neurones, GAP43 – actively growing nerves) or sections were doubled stained (two antibodies or both ISH and IHC).

Results: We have demonstrated that NGF-β is synthesised by the endothelial cells of blood vessels growing into the IVD from the end plate. The high affinity receptor is expressed by those small nerve fibres that accompany the vessels and in their offshoots in pain level discs that are growing from perivascular nerves into the disc. In addition to their expressing the nerve specific molecule PGP9.5, the trk-A positive cells also express the nerve growth associated protein GAP43.

Conclusion: The data indicate that nerve ingrowth into IVD is regulated by NGF-β. We have localised this production to the endothelial cells of ingrowing blood vessels. NGF-β is a potential therapeutic target for the management of back pain.

Introduction: Recent cadaveric studies have identified neovascularisation and neoneuralisation as probable mechanisms in the causation of discogenic pain. Calcium pyrophosphate deposits have been observed in discs in several studies. Their significance in the causation of discogenic pain is unclear. Direct correlation between the pain site and histological features can be verified by aware state endoscopic visualisation.

Aim and Objectives: The study aims to examine and correlate the presence of neovascularisation, crystalline pyrophosphate deposits in the disc, and discogenic pain by spinal probing and discography under endoscopic visualisation.

Material and Methods: Tissue removed from intervertebral discs of 224 patients during surgery was examined directly, and polarised microscopy was used to identify the presence of calcium pyrophosphate and neovascularisation. Their presence was correlated to diagnostic provocative findings of spinal probing and discography and intradiscal distortion during aware state endoscopy.

Results: Calcium Pyrophosphate: Twenty out of 224 patients (9%) demonstrated calcium pyrophosphate in the discs. Fourteen had pain reproduced on probing or discography. Thirteen out of 20 patients (65%) had either an annular collection or leak at the index level. 6 had an extradiscal cause of pain. One hundred percent of the patients with annular collections or leaks had pain on spinal probing or discography. Sixteen patients with pyrophosphate deposits did not have neovascularisation.

Neovascularisation: Thirty seven out of 224 patients (16.5%) showed neovascularisation in the disc. Four discs had crystalline pyrophosphate deposits. Thirty three out of 37 (90%) had pain on probing and/or discography. Out of four patients who had no pain on probing or discography, two had demonstrated tears during previous discographic procedures which were treated with laser annealing. These patients had disc bulges and compressive radiculopathy.

Conclusion: The presence of pyrophosphate in the disc without a tear or leak does not directly render them tender to provocation. The presence of pyrophosphate is not correlated to neovascularisation. Annular tears or leaks are not directly correlated to the presence of pyrophosphates. There is a high correlation between pain provocation and neovascularisation.

Background: Low back pain (LBP) is a major cause of disability. However, current treatments are often empirical and few are directed at the underlying disorder, altered discal cell metabolism, which precipitates the problem. The use of gene therapy to manipulate discal metabolism to treat LBP is an interesting possibility. The Intervertebral disc (IVD) is a therapeutic target in LBP, and one approach to gene therapy would be to isolate IVD chondrocytes (IVDC) and transfer genes ex vivo into these cells. Subsequent reinjection of these genetically altered cells into the lumbar IVD, would permit the expression of the transgene in vivo, generating the therapeutic protein within the IVD.

Methods: To test the viability of this approach, we isolated human IVDC from patients undergoing surgery, grew them ex vivo and transfected them with the marker gene LacZ, using an adenovirus vector and the CMV promoter. Expression of the gene was then measured using X-gal staining for the gene product _-galactosidase. Post infection, some cells were treated with forskolin for 24 hours to assess whether expression of the transgene could be manipulated.

Results: IVDC infected with adenovirus/CMV-LacZ showed maximal LacZ expression 2 days post infection, with almost 50% of cells displaying X-gal positivity. Cells maintained a low level of expression for the remaining 12 days of the study. Control cultures showed no LacZ expression. Cells treated with forskolin after infection with adenovirus/CMV-LacZ exhibited 4 times the level of _-galactosidase activity seen in unstimulated cultures.

Conclusion: This study shows that human IVDC can be transfected with a foreign gene using the adenovirus vector. The gene transduction of a therapeutic gene into IVDC could provide a long lasting effect. In addition, the use of inducible promoters could allow for the autoregulation of gene expression.

Purpose and Background: There is increasing evidence that events within the diseased intervertebral disc (IVD) are mediated by locally synthesised cytokines. A prominent histological, imaging and surgical feature of IVD disease is degradation of the cartilaginous discal matrix. Whilst the mechanism by which this is mediated is unknown, in other situations where connective tissues are degraded degradation is the result of production of matrix-degrading enzymes by local connective tissue cells stimulated by cytokines, particularly the beta isoform of interleukin-1 (IL-1β). Included amongst these disorders is osteoarthritis (OA) of diarthrodial joints. OA has many similarities to the discal “degeneration” seen in mechanical back pain syndromes. In the current study, we have used a combination of in-situ techniques to establish if IL-1β is responsible for stimulating matrix degradation in the IVD.

Methods: Using a combination of radioactive in-situ hybridisation (ISH) and competitive in situ zymography (ISZ) we have studied expression of IL-1β and IL-1R – its type 1 receptor (ISH) and matrix degradation (ISZ) in five diseased lumbar IVD taken at spinal fusion surgery and 10 cadaveric IVD (five normal and five diseased). The nucleus pulposus (NP) was separated from the annulus fibrosus and diced into 0.5cm cubes. Half the cubes (typically three) were fixed in formalin and processed into paraffin wax for ISH, and half were used for ISZ. For ISH, 5 μm sections of paraffin-embedded tissue were reacted with cDNA probes radiolabelled with 35S to 580 and 530 base segments of the IL-1β and IL-1R molecules. Hybridisation was disclosed using autoradiography. For ISZ, 50 μm vibratome sections were placed into wells on microscope slides precoated with gelatin. Sections were incubated for 10 days, half in culture medium and half in medium supplemented with human recombinant IL-1 receptor antagonist (IL-1Ra – an inhibitor of IL-1). Sections were photographed at daily intervals to detect evidence of gel degradation.

Results: Chondrocytes within patient and cadaveric diseased but not normal discs expressed mRNA for both IL-1β and IL-1R. By ISZ, the same cells degraded gelatin. Degradation was inhibited by recombinant IL-1Ra.

Conclusion: This study shows that chondrocytes of diseased discs express IL-1 and its receptor. The same cells produced matrix-degrading enzymes by a mechanism that can be inhibited by the IL-1 inhibitor IL-1Ra. IL-1 is a potential therapeutic target for the management of IV disc disease.

Objective: To analyse the incidence and gravity of reported complications that arise in spinal surgery and assess the comparative safety, or otherwise, of Endoscopic Laser Foraminoplasty.

Methods: The Spinal Foundation, Rochdale, has performed 958 Endoscopic Laser Foraminoplasty procedures and holds a comprehensive database of the results of all operations carried out in this manner. The records of these procedures provided the basis for a comparison of the safety of Endoscopic Laser Foraminoplasty to that found for other spinal surgical techniques as reported in the literature.

Nine hundred and fifty eight procedures have been performed on 716 patients. Complications that arose during the operation and the postoperative phase of six weeks following the procedure were elicited from patient records. This data was correlated and compared to a meta-analysis of randomised controlled trial data available on complications arising during and after conventional spinal surgery. The ‘SPSS’ and ‘CIA’ statistical packages were used to draw conclusions as to the safety of endoscopically assisted laser spinal surgery.

Results: The cohort integrity of operative and review records at six weeks after surgery was 100%. In 958 ELFs performed, 24 complications occurred in 23 patients. There were nine cases of discitis (one infective) (0.9%), one dural tear (0.1%), one deep wound infection (0.1%), two patients suffered a foot drop (one transient) (0.2%), one myocardial infarction (0.1%), one erectile dysfunction (0.1%) and one patient who developed panic attacks post-operatively (0.1%). This amounts to an overall surgical complication rate of 1.6%.

MRI follow up of clinically symptomatic patients highlighted eight residual disc herniations (0.8%).

Meta analysis of randomised controlled trials of conventional spinal surgery for adult onset degenerative disc disease and/or sciatic pain reported overall complication rates for fusion (11.8%), decompression (7.6%), discectomy (6.0%) and chemonucleolysis (9.6%).

Conclusions: The complication rate of Endoscopic Laser Foraminoplasty is shown to be significantly lower than that reported following conventional spinal surgery (P < 0.01). From these results it must therefore be concluded that ELF as a treatment for chronic low back pain and sciatica presents less risk to a patient than conventional methods of spinal surgery.

Introduction: Current diagnostic labels used to dictate the prescription of treatment have been derived from studies of cadavers and surgery performed upon the unconscious patient.

Methods: In 800 patients, feedback during aware state surgery was independently recorded . Pain sources were detected by spinal probing and verified by endoscopy in the extra foraminal, epidural, foraminal and intradiscal zones.

Results: The nerve was found variously painfully tethered to the ascending facet joint, the superior foraminal ligament, superior notch osteophytes, shoulder osteophytes and directly tethered to the disc. In addition, the disc pad, posterior longitudinal ligament and tissues on the dorsum of the vertebra were found to be individually sensitive. These sources produced both local and referred pain.

In two thirds of patients with back pain, the disc itself was quiescent to both external and internal manipulation. In a third of patients, the inflamed nerve produced atypical peripheral radicular symptoms on direct probing.

Discussion: These unrecognised pain sites and the atypical peripheral symptoms they produce may lead to atypical presentations and mal-targeted interventions. Their persistence may account for failures following conventional surgery.

Endoscopy offers an intriguing method of localising and understanding the pathology that underlies diagnostic labels such as failed back syndrome, failed back surgery syndrome, instability and lateral recess stenosis. It is suggested that future surgery be based upon the findings of spinal probing with endoscopic verification.

Dynamic retrolisthesis and olisthesis aggravates inflammation in these foraminal sites.

Perceived knowledge suggests that patients with Failed Back Surgery and a poor psychological profile would respond poorly to surgical interventions. This comparative study was designed to identify if there was a significant difference in the outcome following endoscopic spinal intervention in patients with Failed Back Surgery when compared to those who had no previous interventions.

Between April 1997 and November 1998, 54 patients with failed open back surgery and 85 without previous interventions were included in the study, underwent aware state pain source identification and endoscopic foraminal interventions. Pre- and post-operative assessment at 2 years was made using the Distress and Risk Assessment Method (DRAM), Oswestry Disability Index (ODI) and a Visual Analogue Pain Scale (VAPS). A Mann-Whitney U and Wilcoxon-Signed Rank tests were performed.

Patients with failed back surgery demonstrated greater psychological distress, disability (p < 0.05) and pain pre-operatively than those who underwent primary endoscopic interventions. Post-operatively both groups demonstrated significant improvement and no difference was found in the Zung, DRAM, ODI and VAPS scores.

With aware state pain source identification, targeted minimal intervention and discrete tissue ablation patients with failed back surgery with associated depression can demonstrate favourable physical and psychometric outcomes.

Introduction of new surgical intervention need assessment of the true results by eliminating cognitive dissonance and the placebo effect. Significant time must elapse since the procedure to derive conclusions. With the initial gratifying results of Endoscopic Foraminoplasty a retrospective analysis of the data was performed to identify if the outcome was accurate and not a placebo effect.

Early postoperative Data (6 weeks and 6 months) derived from questionnaires on 91 patients with Endoscopic Foraminoplasty (April 1997 and November 1998), which included the Oswestry Disability Scale and a Visual Analogue Pain Scale was compared with the data at 2 years (late). A t-test was used to assess the difference between the Oswestry Disability scores from the two questionnaires and a Wilcoxon Signed Rank test for the Visual Analogue Pain Scale.

No significant difference between the Visual Analogue Pain Scores at 6 weeks to 6 months and 2 years post-operation was noted. There was however, a marginal improvement (p= 0.05) in Oswestry Index over two years period.

The initial outcome of Endoscopic Laser Foraminoplasty was sustained or improved at the end of two years and was not a placebo effect.

The view that patients low back pain presenting with ‘abnormal’ psychometric and poor DRAM scores predict an unsatisfactory surgical outcome is considered controversial. This prospective study was designed to identify if DRAM Scores (Scores of Distress Risk Assessment Method) is a predictive determinant or a reactive instrument in regard to the outcome of Endoscopic Foraminoplasty.

One hundred and eighty-five patients (86 males and 99 females) underwent an Endoscopic Laser Foraminoplasty between April 1997 and November 1998. Pre- and postoperative assessment at 2 years was made using the Oswestry Disability Scale, and the Visual Analogue Pain Scale and the DRAM scores. Patients were categorised by their pre-op DRAM score. A Kruskal-Wallis analysis of variance and a regression analysis were performed.

There was significant improvement in disability and pain scores at two years. (p< 0.05). A significant difference in median DRAM between the preoperative and postoperative score at two years was noted. While the DRAM score predicted the patients’ disability and pain it failed to predict the change in outcome.

The DRAM score highlights individuals in distress who may need psychological support and physical treatment for optimum benefit from endoscopic spinal intervention and not be used to deny a surgical intervention.

This study evaluates the results of Endoscopic Foraminoplasty on 30 consecutive patients followed for a minimum of 2 years.

The objective has been to assess the efficacy of endoscopic aware state pain source definition combined with endoscopic decompression of the foramen, mobilisation and neurolysis of the exiting and transiting nerves and ablation of osteophytes in patients with spondylolytic spondylolisthesis.

This prospective study involved Endoscopic Foraminoplasty performed on 16 males, and 14 females with an average age of 46 years (36–72 years). They were followed for an average period of 34 months (28–41 months).

One-hundred percent cohort integrity was maintained at the final follow up. Results were analysed using the percentage change in Oswestry Disability Index, and percentage change in visual analogue pain (VAP) scores. Using a percentage change in Oswestry Disability Index of 50 or more to determine good and excellent outcomes, 75% (22 out of 30) exceed this value with five (17%) having 100% benefit for the procedure.

These results indicate that Endoscopic Laser Foraminoplasty provides a minimalist means of exploring the extra-foraminal zone, the listhetic defect, the foramen and its contents, and the epidural space and performing decompression, discectomy, osteophytectomy, perineural neurolysis in patients with spondylolytic-spondylolisthes. Done in an aware state, it serves to identify and localise the source of pain generation.