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The Bone & Joint Journal
Vol. 105-B, Issue 4 | Pages 347 - 355
15 Mar 2023
Birch NC Cheung JPY Takenaka S El Masri WS

Initial treatment of traumatic spinal cord injury remains as controversial in 2023 as it was in the early 19th century, when Sir Astley Cooper and Sir Charles Bell debated the merits or otherwise of surgery to relieve cord compression. There has been a lack of high-class evidence for early surgery, despite which expeditious intervention has become the surgical norm. This evidence deficit has been progressively addressed in the last decade and more modern statistical methods have been used to clarify some of the issues, which is demonstrated by the results of the SCI-POEM trial. However, there has never been a properly conducted trial of surgery versus active conservative care. As a result, it is still not known whether early surgery or active physiological management of the unstable injured spinal cord offers the better chance for recovery. Surgeons who care for patients with traumatic spinal cord injuries in the acute setting should be aware of the arguments on all sides of the debate, a summary of which this annotation presents.

Cite this article: Bone Joint J 2023;105-B(4):347–355.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_12 | Pages 12 - 12
1 Dec 2022
Shadgan B Kwon B
Full Access

Despite advances in treating acute spinal cord injury (SCI), measures to mitigate permanent neurological deficits in affected patients are limited. Augmentation of mean arterial blood pressure (MAP) to promote blood flow and oxygen delivery to the injured cord is one of the only currently available treatment options to potentially improve neurological outcomes after acute spinal cord injury (SCI). However, to optimize such hemodynamic management, clinicians require a method to measure and monitor the physiological effects of these MAP alterations within the injured cord in real-time. To address this unmet clinical need, we developed a series of miniaturized optical sensors and a monitoring system based on multi-wavelength near-infrared spectroscopy (MW-NIRS) technique for direct transdural measurement and continuous monitoring of spinal cord hemodynamics and oxygenation in real-time. We conducted a feasibility study in a porcine model of acute SCI. We also completed two separate animal studies to examine the function of the sensor and validity of collected data in an acute experiment and a seven-day post-injury survival experiment. In our first animal experiment, nine Yorkshire pigs underwent a weight-drop T10 vertebral level contusion-compression injury and received episodes of ventilatory hypoxia and alterations in MAP. Spinal cord hemodynamics and oxygenation were monitored throughout by a transdural NIRS sensor prototype, as well as an invasive intraparenchymal (IP) sensor as a comparison. In a second experiment, we studied six Yucatan miniature pigs that underwent a T10 injury. Spinal cord oxygenation and hemodynamics parameters were continuously monitored by an improved NIRS sensor over a long period. Episodes of MAP alteration and hypoxia were performed acutely after injury and at two- and seven-days post-injury to simulate the types of hemodynamic changes patients experience after an acute SCI. All NIRS data were collected in real-time, recorded and analyzed in comparison with IP measures. Noninvasive NIRS parameters of tissue oxygenation were highly correlated with invasive IP measures of tissue oxygenation in both studies. In particular, during periods of hypoxia and MAP alterations, changes of NIRS-derived spinal cord tissue oxygenation percentage were significant and corresponded well with the changes in spinal cord oxygen partial pressures measured by the IP sensors (p < 0.05). Our studies indicate that a novel optical biosensor developed by our team can monitor real-time changes in spinal cord hemodynamics and oxygenation over the first seven days post-injury and can detect local tissue changes that are reflective of systemic hemodynamic changes. Our implantable spinal cord NIRS sensor is intended to help clinicians by providing real-time information about the effects of hemodynamic management on the injured spinal cord. Hence, our novel NIRS system has the near-term potential to impact clinical care and improve neurologic outcomes in acute SCI. To translate our studies from bench to bedside, we have developed an advanced clinical NIRS sensor that is ready to be implanted in the first cohort of acute SCI patients in 2022


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_III | Pages 460 - 460
1 Aug 2008
Elwell V Sutcliffe J Akmal M
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Objective: The purpose of this study was to assess whether the use of high dose methylprednisolone (MPS) given to trauma patients with acute spinal cord injury improves neurological and long term functional outcomes. Summary of Background Data: The National Acute Spinal Cord Injury Studies (NASCIS II and III) recommend the early administration of high dose MPS in the context of acute spinal cord injury. However, controversy exists surrounding its long term benefits. Methods: A retrospective data analysis was performed using the Helicopter Emergency Medical Service (HEMS) trauma registry, medical records, and rehabilitation notes of 263 trauma patients with acute spinal injury admitted over a 6-year period. All survivors over 16 years of age with documented spinal cord injuries were selected. Frankel grade, Injury Severity Score (ISS), and Functional Independence Measure (FIM) scores (minimum FIM of 18 implies total dependence, and a maximum of 126 implies no disability) as indicators of neurological and functional morbidity were recorded at initial presentation, hospital discharge, and intervals up to 12 months post injury. Details of the age, gender, mechanism of injury, nature of injury and associated injuries were also recorded. Results: There were 139 patients (107 males and 32 women) with documented acute spinal cord injuries, of which 74 patients had neurological deficits (Frankel A–D) at presentation. 49 patients were given high dose MPS within 8 hours of injury according to a standard protocol. The remaining 25 patients with documented neurological injury did not meet criteria or failed to receive the agent within the recommended time. The mean ISS scores were shown to be comparable in both groups. 59% (29/49) of patients who were given MPS showed an improvement of one or greater Frankel grade at the time of discharge whereas 52% (13/25) of patients who did not receive MPS showed a similar improvement in Frankel grades. We had long term functional outcome data (FIM scores) on 48% (67/139) of the total number of patients. At the time of discharge, the mean FIM scores for the MPS treated group and non MPS treated group were 68 and 90, respectively. Whereas at 12 months, there was no significant difference in the mean FIM scores between the two groups (both of which were > 100). Conclusions: The Frankel grade assesses the degree of neurological impairment while FIM scores are a basic measure of the severity of disability regardless of the underlying impairment. In our study, patients given high dose MPS in the context of acute spinal cord injury showed some early improvement in Frankel grades. However, we have shown, there is no short term or long term benefit in terms of functional outcome by using MPS in trauma patients with acute spinal cord injury


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 3 - 3
1 Sep 2012
Lee R Lee R Dvorak M Kwon B
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Introduction. While there is a desperate need for effective treatments for acute spinal cord injury (SCI), the clinical validation of novel therapeutic interventions is severely hampered by the need to recruit relatively large numbers of patients into clinical trials for sufficient statistical power. While a centre might annually admit 100 acute SCI patients, only a fraction may satisfy the basic inclusion criteria for an acute clinical trial, which typically requires patients of a certain injury severity (eg ASIA A), within a specific time window (eg. 12 hours from injury), and without other major injuries or conditions that would cloud the baseline neurologic assessment. This study was conducted to define that “fraction” of SCI patients that would theoretically satisfy standard inclusion criteria of an acute clinical trial. Methods. Using a local database, we reviewed patients admitted to our Level 1 trauma center with a complete (ASIA A) or an incomplete (ASIA B, C and D) acute SCI involving bony spinal levels between C0 and sacrum. All patients admitted over the 4 year period from 2005 to 2009 were reviewed. Demographic information and data about the patients' SCI and other injuries were reviewed. We then determined how many of the total number of SCI patients would be eligible for enrolment into a hypothetical acute clinical trial that required a valid baseline assessment of neurologic impairment, and an enrolment window of either 12 hours, 24 hours, or 48 hours. Results. 408 acute traumatic SCI patients were admitted over the 4 year period. 253 of 408 (62%) patients presented within 12 hours of injury, 60 (15%) between 12–24 hours, and 28 (7%) between 24–48 hours. 42% of patients were ASIA A, 13% B, 18% C and 27% D. The number of patients who presented with injuries or other conditions that would exclude them from enrolment was relatively high: 4% had penetrating injuries, 12% had illicit drug use, and 20% had either alcohol intoxication or head injuries which precluded a valid baseline neurologic examination. Conclusions. Out of a total of 408 patients admitted over 4 years, the number who would have been optimistically eligible for an acute neuroprotective trial was disappointingly small. Given that acute clinical trials are increasingly interested in cervical ASIA A patients (in whom segmental motor recovery can be assessed), the number of such patients who would actually be eligible for an acute intervention was surprisingly low. Given that additional inclusion/exclusion criteria would also be applicable in a real clinical trial, the true number of “eligible” or “recruitable” patients is conservatively even lower. This study is the first to quantify this challenging aspects of conducting acute SCI clinical trials, and provides valuable information for those planning such initiative


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_II | Pages 100 - 100
1 Feb 2003
Molloy S Middleton FRI Casey ATH
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The NASCIS studies reported improved long-term neurological recovery when high dose methylprednisolone was administered following spinal cord injury.

To determine if there is correct implementation of the NASCIS protocols. Prospective observational study. The admission Frankel grade and ASIA neurological classification were recorded.

100 patients with complete or incomplete spinal cord injuries were studied during a 24 month period.

Outcome Measures: Correct administration of methyprednisolone.

The mean ASIA score was 192 and median Frankel grade was C. Only 25% of the patients received methyl-prednisolone according to the NASCIS regime.

“Evidence Based Medicine” is not being adopted.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_23 | Pages 88 - 88
1 Dec 2016
Kreutzträger M Kopp M Nikolai S Ekkernkamp A Niedeggen A Thomas L
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Aim

Spinal infections with and without aSCI represent a severe disease with a high lethality rate of up to 17%. The current treatment recommendations include an antimicrobial therapy and if necessary in combination with operative procedures. Aims of this study are the analysis of risk factors and treatment concepts and to compare the outcome of patients suffering a spinal infection with and without an aSCI.

Method

Monocentric prospective case study from 2013 – 2015. Patients were examined using a diagnostic algorithm (CT-thorax/abdomen, MRI total-spine, blood cultures, dental chart, echocardiogram). A calculated antimicrobial therapy was initially administered and later changed according to the antibiotic resistance. Additional operative procedures were performed with respect to the clinical and radiological findings.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_12 | Pages 71 - 71
1 Dec 2022
Pelletier-Roy R Dionne A Richard-Denis A Briand M Bourassa-Moreau E Mac-Thiong J
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Acute spinal cord injury (SCI) is most often secondary to trauma, and frequently presents with associated injuries. A neurological examination is routinely performed during trauma assessment, including through Advanced Trauma Life Support (ATLS). However, there is no standard neurological assessment tool specifically used for trauma patients to detect and characterize SCI during the initial evaluation. The International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) is the most comprehensive and popular tool for assessing SCI, but it is not adapted to the acute trauma patients such that it is not routinely used in that setting. Therefore, the objective is to develop a new tool that can be used routinely in the initial evaluation of trauma patients to detect and characterize acute SCI, while preserving basic principles of the ISNCSCI. The completion rate of the ISCNSCI during the initial evaluation after an acute traumatic SCI was first estimated. Using a modified Delphi technique, we designed the Montreal Acute Classification of Spinal Cord Injuries (MAC-SCI), a new tool to detect and characterize the completeness (grade) and level of SCI in the polytrauma patient. The ability of the MAC-SCI to detect and characterize SCI was validated in a cohort of 35 individuals who have sustained an acute traumatic SCI. The completeness and neurological level of injury (NLI) were assessed by two independent assessors using the MAC-SCI, and compared to those obtained with the ISNCSCI. Only 33% of patients admitted after an acute traumatic SCI had a complete ISNCSCI performed at initial presentation. The MAC-SCI includes 53 of the 134 original elements of the ISNCSCI which is 60% less. There was a 100% concordance between the severity grade derived from the MAC-SCI and from the ISNCSCI. Concordance of the NLI within two levels of that obtained from the ISNCSCI was observed in 100% of patients with the MAC-SCI and within one level in 91% of patients. The ability of the MAC-SCI to discriminate between cervical (C0 to C7) vs. thoracic (T1 to T9) vs. thoraco-lumbar (T10 to L2) vs. lumbosacral (L3 to S5) injuries was 100% with respect to the ISNCSCI. The rate of completion of the ISNCSCI is low at initial presentation after an acute traumatic SCI. The MAC-SCI is a streamlined tool proposed to detect and characterize acute SCI in polytrauma patients, that is specifically adapted to the acute trauma setting. It is accurate for determining the completeness of the SCI and localize the NLI (cervical vs. thoracic vs. lumbar). It could be implemented in the initial trauma assessment protocol to guide the acute management of SCI patients


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_12 | Pages 8 - 8
1 Dec 2022
Pelletier-Roy R Dionne A Richard-Denis A Briand M Bourassa-Moreau E Mac-Thiong J
Full Access

Acute spinal cord injury (SCI) is most often secondary to trauma, and frequently presents with associated injuries. A neurological examination is routinely performed during trauma assessment, including through Advanced Trauma Life Support (ATLS). However, there is no standard neurological assessment tool specifically used for trauma patients to detect and characterize SCI during the initial evaluation. The International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) is the most comprehensive and popular tool for assessing SCI, but it is not adapted to the acute trauma patients such that it is not routinely used in that setting. Therefore, the objective is to develop a new tool that can be used routinely in the initial evaluation of trauma patients to detect and characterize acute SCI, while preserving basic principles of the ISNCSCI. The completion rate of the ISCNSCI during the initial evaluation after an acute traumatic SCI was first estimated. Using a modified Delphi technique, we designed the Montreal Acute Classification of Spinal Cord Injuries (MAC-SCI), a new tool to detect and characterize the completeness (grade) and level of SCI in the polytrauma patient. The ability of the MAC-SCI to detect and characterize SCI was validated in a cohort of 35 individuals who have sustained an acute traumatic SCI. The completeness and neurological level of injury (NLI) were assessed by two independent assessors using the MAC-SCI, and compared to those obtained with the ISNCSCI. Only 33% of patients admitted after an acute traumatic SCI had a complete ISNCSCI performed at initial presentation. The MAC-SCI includes 53 of the 134 original elements of the ISNCSCI which is 60% less. There was a 100% concordance between the severity grade derived from the MAC-SCI and from the ISNCSCI. Concordance of the NLI within two levels of that obtained from the ISNCSCI was observed in 100% of patients with the MAC-SCI and within one level in 91% of patients. The ability of the MAC-SCI to discriminate between cervical (C0 to C7) vs. thoracic (T1 to T9) vs. thoraco-lumbar (T10 to L2) vs. lumbosacral (L3 to S5) injuries was 100% with respect to the ISNCSCI. The rate of completion of the ISNCSCI is low at initial presentation after an acute traumatic SCI. The MAC-SCI is a streamlined tool proposed to detect and characterize acute SCI in polytrauma patients, that is specifically adapted to the acute trauma setting. It is accurate for determining the completeness of the SCI and localize the NLI (cervical vs. thoracic vs. lumbar). It could be implemented in the initial trauma assessment protocol to guide the acute management of SCI patients


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 43 - 43
1 Dec 2022
Pelletier-Roy R Dionne A Richard-Denis A Briand M Bourassa-Moreau E Mac-Thiong J
Full Access

Acute spinal cord injury (SCI) is most often secondary to trauma, and frequently presents with associated injuries. A neurological examination is routinely performed during trauma assessment, including through Advanced Trauma Life Support (ATLS). However, there is no standard neurological assessment tool specifically used for trauma patients to detect and characterize SCI during the initial evaluation. The International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) is the most comprehensive and popular tool for assessing SCI, but it is not adapted to the acute trauma patients such that it is not routinely used in that setting. Therefore, the objective is to develop a new tool that can be used routinely in the initial evaluation of trauma patients to detect and characterize acute SCI, while preserving basic principles of the ISNCSCI. The completion rate of the ISCNSCI during the initial evaluation after an acute traumatic SCI was first estimated. Using a modified Delphi technique, we designed the Montreal Acute Classification of Spinal Cord Injuries (MAC-SCI), a new tool to detect and characterize the completeness (grade) and level of SCI in the polytrauma patient. The ability of the MAC-SCI to detect and characterize SCI was validated in a cohort of 35 individuals who have sustained an acute traumatic SCI. The completeness and neurological level of injury (NLI) were assessed by two independent assessors using the MAC-SCI, and compared to those obtained with the ISNCSCI. Only 33% of patients admitted after an acute traumatic SCI had a complete ISNCSCI performed at initial presentation. The MAC-SCI includes 53 of the 134 original elements of the ISNCSCI which is 60% less. There was a 100% concordance between the severity grade derived from the MAC-SCI and from the ISNCSCI. Concordance of the NLI within two levels of that obtained from the ISNCSCI was observed in 100% of patients with the MAC-SCI and within one level in 91% of patients. The ability of the MAC-SCI to discriminate between cervical (C0 to C7) vs. thoracic (T1 to T9) vs. thoraco-lumbar (T10 to L2) vs. lumbosacral (L3 to S5) injuries was 100% with respect to the ISNCSCI. The rate of completion of the ISNCSCI is low at initial presentation after an acute traumatic SCI. The MAC-SCI is a streamlined tool proposed to detect and characterize acute SCI in polytrauma patients, that is specifically adapted to the acute trauma setting. It is accurate for determining the completeness of the SCI and localize the NLI (cervical vs. thoracic vs. lumbar). It could be implemented in the initial trauma assessment protocol to guide the acute management of SCI patients


The Bone & Joint Journal
Vol. 105-B, Issue 4 | Pages 400 - 411
15 Mar 2023
Hosman AJF Barbagallo G van Middendorp JJ

Aims. The aim of this study was to determine whether early surgical treatment results in better neurological recovery 12 months after injury than late surgical treatment in patients with acute traumatic spinal cord injury (tSCI). Methods. Patients with tSCI requiring surgical spinal decompression presenting to 17 centres in Europe were recruited. Depending on the timing of decompression, patients were divided into early (≤ 12 hours after injury) and late (> 12 hours and < 14 days after injury) groups. The American Spinal Injury Association neurological (ASIA) examination was performed at baseline (after injury but before decompression) and at 12 months. The primary endpoint was the change in Lower Extremity Motor Score (LEMS) from baseline to 12 months. Results. The final analyses comprised 159 patients in the early and 135 in the late group. Patients in the early group had significantly more severe neurological impairment before surgical treatment. For unadjusted complete-case analysis, mean change in LEMS was 15.6 (95% confidence interval (CI) 12.1 to 19.0) in the early and 11.3 (95% CI 8.3 to 14.3) in the late group, with a mean between-group difference of 4.3 (95% CI -0.3 to 8.8). Using multiply imputed data adjusting for baseline LEMS, baseline ASIA Impairment Scale (AIS), and propensity score, the mean between-group difference in the change in LEMS decreased to 2.2 (95% CI -1.5 to 5.9). Conclusion. Compared to late surgical decompression, early surgical decompression following acute tSCI did not result in statistically significant or clinically meaningful neurological improvements 12 months after injury. These results, however, do not impact the well-established need for acute, non-surgical tSCI management. This is the first study to highlight that a combination of baseline imbalances, ceiling effects, and loss to follow-up rates may yield an overestimate of the effect of early surgical decompression in unadjusted analyses, which underpins the importance of adjusted statistical analyses in acute tSCI research. Cite this article: Bone Joint J 2023;105-B(4):400–411


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_II | Pages 169 - 169
1 Jul 2002
Ampat G
Full Access

To determine the current practice and to review the literature regarding administration of high dose Methylprednisolone for acute spinal cord injury (SCI). Administration of high dose Methylprednisolone for Acute Spinal Cord Injury has been widely practised following the publication of the three National Acute Spinal Cord Injury Studies (NASCIS). NASCIS recommends a bolus intravenous dose of 30mg/kg of Methylprednisolone in 15 minutes, followed by a 45 min pause and then followed by a maintenance dose of 5.4 mg / kg / hr for 23 hours. This regime has been recommended by the Advanced Trauma Life Support. The Cochrane reviews also extol the three NASCIS randomised controlled trials. The mechanism of neuroprotection by Methylprednisolone is based on its inhibition of lipid peroxidation. Three hundred questionnaires were sent to Consultants practising Spinal surgery, Neurosurgery and Accident & Emergency to determine the popular thought regarding the use of Methylprednisolone for Acute SCI. A thorough review of current medical literature was also performed. The literature search showed contradictory evidence regarding the use of high dose Methylprednisolone. The current popular thought, the diversity of responses between the three groups, the results of the 3 NASCIS trials and a recent review of literature is presented


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_15 | Pages 12 - 12
7 Nov 2023
Kruger N Arnolds D Dunn R
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To analyse the causes and factors associated with mortality in patients admitted to ASCI unit in a low- or middle-income country. The study was performed at a Tertiary Hospital at Groote Schuur Hospital, Cape Town South Africa. Data between 1996 –2022 were retrospectively collected from hospital records of patients admitted to the ASCI Unit. There was approximately 3223 admissions for the study period. 682 patients were confirmed dead 87% were male and 64% were unemployed. The mean age was 46 years (ranging from 14 – 87 years). A 1/3 of injuries were caused by a MVA, a ¼ by a fall (low energy and from a height), and 1/5 by a gunshot wound. Average length of stay was 47 days (SD = 52 days), ranging from as short as 1 day to 512 days for one patient. Majority (65%) were admitted for more than a week but less than 2 months 32% were ventilated, and 17% with a CPAP facemask. 10% of patients had a pre-existing ulcer prior to admission. 65% of patients had surgery via the posterior approach, 33% via the anterior approach. On average patients died within 5 years of being admitted to hospital, ranging from dying in the same year as the injury to 20 years later. 73% of the deaths were classified as natural deaths and 20% as unnatural. There is a high mortality in patients with acute spinal cord injury, causes are multifactorial, and in depth critical analyses is required to improve clinical outcomes and rationalise resource allocation


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 131 - 131
1 Mar 2006
Quinlan J Watson R Kelly P OByrne J Fitzpatrick J
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Increased bone turnover and fracture healing is associated with acute spinal cord injuries. Experimental work to date has been confined to animal models. While the benefits in relation to quicker fracture healing are obvious, this excessive bone growth (heterotopic ossification) also causes unwanted side effects, such as decreased movement around joints, joint fusion and renal tract calculi. This paper evaluates two groups of patients with spinal column fractures – those with neurological compromise and those without, and compares them with a control group with isolated long bone fractures. Serum was taken from these patients at 10 days post injury and was analysed for the known osteogenic cytokines Insulin-like Growth Factor-1 (IGF-1) and Transforming Growth Factor-b1 (TGF-b1) as well as being added to an osteoblast cell culture line to analyse cell proliferation. The results for the IGF-1 show a higher level in the neurology group compared to the no neurology group (p=0.038). In the TGF-B1 assay, the neurology group has a lower level than the other two groups (p< 0.0001 and p=0.002 respectively). However, when this group is subdivided into patients with complete and incomplete neurology, it can be seen that the levels of the complete group are elevated, although not significantly so (p=0.228). All three groups stimulated markedly increased osteoblast cell proliferation versus a control group (p=0.086, p=0.005 and p=0.002 respectively). However, the neurology group is significantly lower than the other two groups (p=0.007 and p=0.001 respectively). Furthermore the complete group causes a lower proliferation rate than the incomplete group (p=0.539). In conclusion, at 10 days post injury when the acute inflammatory reaction is subsiding and new bone is being laid down, patients with acute spinal cord injuries have increased bone turnover. This increase is being indirectly mediated by IGF-1, and more elevated levels with more severe neurological compromise suggest a contributory role of TGF-b1. Direct stimulation of osteoblasts does not appear to have any role to play in this accelerated bone healing


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_I | Pages 87 - 88
1 Jan 2004
Newcombe R Blumbergs P Manavis J Jones N
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Introduction: Apoptosis, or secondary cell death, has been demonstrated in a number of neurological conditions, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and brain ischaemia. It is well established from studies of acute spinal cord injury that apoptosis seems an important factor in secondary cell death and irreversible neurological deficit. It is only recently that studies have emerged analysing secondary cell death in chronic injury to the cord. In this study, the spatial and temporal expression of apoptotic cells was analysed in acute traumatic spinal cord injury (SCI) (n=6) and chronic myelopathies due to metastatic tumour (n=5), degenerative spondylosis (n=6) and syringomyelia (n=4). The study aimed to demonstrate apoptosis in compressive spinal cord injury and to analyse the spatial and temporal distribution of apoptosis in acute and chronic myelopathy. Method: Archival material from 21 spinal cords of patients with documented myelopathy during life and definitive evidence on post mortem examination were available for study. The spatial and temporal expression of apoptotic cells was analysed in acute traumatic spinal cord injury (SCI) (n=6) and chronic myelopathy due to metastatic tumour (n=5), degenerative spondylosis (n=6) and syringomyelia (n=4). Immunohistochemical analysis of each specimen was conducted using markers of apoptosis, as well as the biochemical apoptotic marker TUNEL. A total of 1800 histopathological slides were analysed. Specimens were also analysed using confocal microscopy to identify the immunopositive cell type. A combination of morphological, immunohistochemical and in situ end-labelling techniques were used to investigate the mechanism of cell death in this experiment. The analytical techniques employed were aimed at showing firstly the presence of apoptosis and secondly the size and position of the damaged regions. Results: Positivity for active Caspase-3, DNA-PKCS, PARP, TUNEL and active Caspase-9 was found in glia (oligodendrocytes and microglia) axons and neurons in both acute and chronic compression above, below and at the site of compression. In chronic compression, the severity of positivity for apoptotic immunological markers was positively correlated with the severity of white matter damage, as measured by APP immunostaining for axonal injury, and Wallerian degeneration. There was no correlation between the duration of chronic compression and immunopositivity for apoptotic markers. In acute SCI, axonal swellings were consistently positive for Caspases −9 and -3, suggesting mitochondrial activation of apoptotic pathways. Conclusion: Apoptosis occurs in both acute and chronic spinal cord injury. In acute compression, axonal injury is associated with apoptotic immunopositivity of glia and neurons. In chronic compression, apoptosis of oligodendrocytes and microglia correlates with demyelination of axons within the white matter


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_III | Pages 283 - 283
1 Mar 2003
Newcombe R Blumbergs P Manavis J Jones N
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INTRODUCTION: Apoptosis, or secondary cell death, has been demonstrated in a number of neurological conditions, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and brain ischaemia. It is well established from studies of acute spinal cord injury that apoptosis seems an important factor in secondary cell death and irreversible neurological deficit. It is only recently that studies have emerged analysing secondary cell death in chronic injury to the cord. In this study, the spatial and temporal expression of apoptotic cells was analysed in acute traumatic spinal cord injury (SCI) (n=6) and chronic myelopathies due to meta-static tumour (n=5), degenerative spondylosis (n=6) and syringomyelia (n=4). The study aimed to demonstrate apoptosis in compressive spinal cord injury and to analyse the spatial and temporal distribution of apoptosis in acute and chronic myelopathy. METHOD: Archival material from 21 spinal cords of patients with documented myelopathy during life and definitive evidence on post mortem examination were available for study. The spatial and temporal expression of apoptotic cells was analysed in acute traumatic spinal cord injury (SCI) (n=6) and chronic myelopathy due to metastatic tumour (n=5), degenerative spondylosis (n=6) and syringomyelia (n=4). Immunohistochemical analysis of each specimen was conducted using markers of apoptosis, as well as the biochemical apoptotic marker TUNEL. A total of 1800 histopathological slides were analysed. Specimens were also analysed using confocal microscopy to identify the immunopositive cell type. A combination of morphological, immunohistochemical and in situ end-labelling techniques were used to investigate the mechanism of cell death in this experiment. The analytical techniques employed were aimed at showing firstly the presence of apoptosis and secondly the size and position of the damaged regions. RESULTS: Positivity for active Caspase-3, DNA-PKCS, PARP, TUNEL and active Caspase-9 was found in glia (oligodendrocytes and microglia) axons and neurons in both acute and chronic compression above, below and at the site of compression. In chronic compression, the severity of positivity for apoptotic immunological markers was positively correlated with the severity of white matter damage, as measured by APP immunostaining for axonal injury, and Wallerian degeneration. There was no correlation between the duration of chronic compression and immunopositivity for apoptotic markers. In acute SCI, axonal swellings were consistently positive for Caspases −9 and -3, suggesting mitochon-drial activation of apoptotic pathways. CONCLUSION: Apoptosis occurs in both acute and chronic spinal cord injury. In acute compression, axonal injury is associated with apoptotic immunopositivity of glia and neurons. In chronic compression, apoptosis of oligodendrocytes and microglia correlates with demyelination of axons within the white matter


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_II | Pages 61 - 61
1 Feb 2012
Quinlan J Watson R Kelly P O'Byrne J Fitzpatrick J
Full Access

Patients with spinal cord injuries have been seen to have increased healing of attendant fractures. This for the main has been a clinical observation with laboratory work confined to rats. While the benefits in relation to quicker fracture healing are obvious, this excessive bone growth (heterotopic ossification) also causes unwanted side effects, such as decreased movement around joints, joint fusion and renal tract calculi. However, the cause for this phenomenon remains unclear. This paper evaluates two groups with spinal column fractures – those with neurological compromise (n=10) and those without (n=15), and compares them with a control group with isolated long bone fractures (n=12). Serum was taken from these patients at five specific time intervals post injury (1 day, 5 days, 10 days, 42 days (6 weeks) and 84 days (12 weeks)). These samples were then analysed for levels of Transforming Growth Factor-Beta (TGF-β using the ELISA technique. This cytokine has been shown to stimulate bone formation after both topical and systemic administration. Results show TGF-β levels of 142.79+/-29.51 ng/ml in the neurology group at 84 days post injury. This is higher than any of the other time points within this group (p=0.009 vs. all other time points, ANOVA). Furthermore, this level is also higher than the levels recorded in the no neurology (103.51+/-36.81 ng/ml) and long bone (102.28=/-47.58 ng/ml) groups at 84 days post-injury (p=0.009 and p=0.04 respectively, ANOVA). In conclusion, the results of this work, carried out for the first time in humans, offers strong evidence of the causative role of TGF-β in the increased bone turnover and attendant complications seen in patients with acute spinal cord injuries


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 202 - 202
1 Mar 2010
Quinlan J Watson R Kelly G Kelly P O’Byrne J Fitzpatrick J
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Patients with spinal cord injuries have been seen to have increased healing of attendant fractures. While the benefits are obvious, this excessive bone growth also causes unwanted side effects, such as decreased movement around joints, joint fusion and renal tract calculi. However, the cause for this phenomenon remains unclear. This paper evaluates two groups with spinal column fractures – those with neurological compromise (n=10) and those without (n=15), and compares them with a control group with isolated long bone fractures (n=12). Serum was taken from these patients at five specific time intervals post injury (1 day, 5 days, 10 days, 42 days (6 weeks) and 84 days(12 weeks)). These samples were then analysed for levels of Transforming Growth Factor-Beta (TGF-.) using the ELISA technique. This cytokine has been shown to stimulate bone formation after both topical and systemic administration. Results show TGF-.; levels of 142.79±29.51 ng/ml in the neurology group at 84 days post injury. This is higher than any of the other time points within this group (.0.009 vs. all other time points, ANOVA). Furthermore, this level is also higher than the levels recorded in the no neurology (103.51±36.81 ng/ml) and long bone (102.28±47.58 ng/ml) groups at 84 days post injury (p=0.009 and p=0.04 respectively, ANOVA). In conclusion, the results of this work, carried out for the first time in humans, offers strong evidence of the causative role of TGF-.; in the increased bone turnover and attendant complications seen in patients with acute spinal cord injuries


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 319 - 320
1 Sep 2005
Reilly C Mulpuri K
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Introduction and Aims: The aim of this paper is to review C1-C2 facet screw use in paediatric patients and to demonstrate that the technique plays an important role in patients with underlying anatomic abnormalities, which are common in children with cervical instability. Method: A chart review was conducted of all patients managed with C1-C2 facet screws from January 1, 1996 until July 30, 2003 present in the case database. All radiographs were obtained and reviewed. Post-operative and follow-up films were assessed for acceptable screw position and evidence of fusion. Results: C1-C2 facet screws were utilised in nine patients at British Columbia’s Children’s Hospital. The youngest patient treated was five years of age with a mean age for the group of 12. The group consisted of three Down syndrome patients and six with Os Odontoidium, two of which failed previous C1-C2 fusion. Two patients presented with an acute spinal cord injury. Pre-operative CT or MR imaging was used in all patients. Screw placement was unacceptable in one case. Post-operative Halo immobilisation was used in seven patients. Post-operative complications included one wound infection and four halo pin infections requiring treatment. No patients have required surgery at a mean follow-up of four years. C1-C2 facet screws are an important adjunct in a paediatric spine practice. This technique has a great advantage in Down syndrome patients who have a high rate of pseudoarthosis because of: ligamentous laxity, non-compliance with immobilisation and a high incidence of congenital deformities such as os odontoidium and incomplete posterior arch of C1. Conclusion: C1-C2 facet screws can be safely used in young children. The screws allow for fixation in the absence of an intact posterior arch. The technique has a great advantage in Down syndrome patients who have a high rate of pseudoarthosis due to congenital deformities, ligamentous laxity and non-compliance with immobilisation


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_III | Pages 456 - 456
1 Aug 2008
Jariwala A Borremans J Kluger P
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The current work compares, in the patients with acute spinal cord injuries (SCI), the rate of early complications in those who were operated ‘out of hours’ to the patients who had their surgical interventions performed on the elective trauma list. In a two-year study, all the complications occurring within the first month of surgery were recorded. Patients who had their operative procedure between 22.00 pm and 8.00 am comprised the ‘out of hours’ group, while the other group included patients operated on daytime spinal trauma lists. Each group had 22 patients. The demographics, injury patterns, time relapse to admission and theatre, the surgical procedure, its duration, the postoperative results and early complications were retrospectively analysed and compared for the two groups. There were 38 males. 20 patients had complete SCI and 26 had thoracic spine involvement. Road traffic accident was the cause of injury in 26 patients. Two patients received steroids following the injury. The average admission time was 3 days. Surgery occurred on an average within 48 h (range 1–20 days). The mean theatre time was 2.8 h for the emergency group and 3.4 h for the elective cases. Early postoperative complications were chest infections (5), urinary tract infections (7), superficial wound infections (2), and pulmonary embolism (1). The incidence of complications was higher in cervical injuries, polytrauma, complicated procedures and individuals requiring intensive care. No significant differences were noted between the two groups. Operating non life-saving emergency cases on elective list constitutes good clinical practice. Various reviews including the National Confidential Enquiry into Patient Outcomes and Deaths (NCEPOD) suggest that operating out of working hours poses a substantial risk to the patient’s health and safety. This study emphasizes that complications relate to the injury level, associated injuries and the procedure itself, rather than to the timing of surgery


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 143 - 143
1 Mar 2006
Quinlan J Watson R Kelly P OByrne J Fitzpatrick J
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Patients with spinal cord injuries have been seen to have increased healing of attendant fractures. This for the main has been a clinical observation with laboratory work confined to rats. While the benefits in relation to quicker fracture healing are obvious, this excessive bone growth (heterotopic ossification) also causes unwanted side effects, such as decreased movement around joints, joint fusion and renal tract calculi. However, the cause for this phenomenon remains unclear. This paper evaluates two groups with spinal column fractures – those with neurological compromise (n=10) and those without (n=11), and compares them with a control group with isolated long bone fractures (n=10). Serum was taken from these patients at five specific time intervals post injury (1 day, 5 days, 10 days, 42 days (6 weeks) and 84 days(12 weeks)). These samples were then analysed for levels of Transforming Growth Factor-Beta (TGF-b) using the ELISA technique. This cytokine has been shown to stimulate bone formation after both topical and systemic administration. Results show TGF-b levels of 142.79+/−29.51 ng/ml in the neurology group at 84 days post injury. This is higher than any of the other time points within this group (p< 0.001 vs. day 1, day 5 and day 10 and p=0.005 vs. 42 days, ANOVA univariate analysis). Furthermore, this level is also higher than the levels recorded in the no neurology (103.51+/−36.81 ng/ml) and long bone (102.28=/−47.58 ng/ml) groups at 84 days post injury (p=0.011 and p=0.021 respectively, ANOVA univariate analysis). There was statistically significant difference in TGF-b levels seen between the clinically more severely injured patients i.e. complete neurological deficit and the less severely injured patients i.e. incomplete neurological deficit. In conclusion, the results of this work, carried out for the first time in humans, offers strong evidence of the causative role of TGF-b in the increased bone turnover and attendant complications seen in patients with acute spinal cord injuries