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Retrospective study.The importance of attenuating the cardiovascular autoregulatory disturbances accompanying acute spinal cord injury (SCI) has long been recognised. This report assembles SCI emergency service data and correlates cardiovascular parameters to preserved functional neuroanatomy.The nascent nature of evidence-based reporting of prehospital cardiovascular autoregulatory disturbances in SCI indicates the need to assemble more information.SCI data for24 h were extracted from ambulance and hospital records. The mean arterial pressure (MAP) was calculated. The International Standard for Neurological Classification of SCI (ISNCSCI) evaluates the primary outcome of motor incomplete injury (grades C/D) at acute presentation. Logistic regression was adjusted for multiple confounders that were expected to influence the odds of grade C/D.A cohort of 99 acute SCI cases was retained; mean (SD) age 40.7±20.5 yrs, 88 male, 84 tetraplegic, 65 Grades A/B (motor complete injury), triage time 2±1.6 hrs. The lowest recorded prehospital MAP (mean [SD] 77.9±19, range 45-145 mmHg) approached the nadir for adequate organ perfusion. Thirty-four (52%) grade A/B and 10 (30%) C/D cases had MAP readings85 mmHg. In data adjusted for age, injury level, and triage time a 5 mmHg increase in the lowest MAP value was associated with a 34% increase in the odds of having motor incomplete injury at acute presentation (adjusted OR=1.34; 95% CI 1.11, 1.61; P=0.002).An important observation with implications for timely and selective cardiovascular resuscitation during SCI prehospital care involves significant negative associations between the depth of systemic hypotension and preserved functional neuroanatomy. Regardless of the mechanism, our confounder-adjusted logistic regression model extends in-hospital evidence and provides a conceptual bedside-bench framework for future investigations.

Clinical trials evaluating early therapies after spinal cord injury (SCI) are challenging because of the absence of a rapid assessment. The aim of this study was to determine whether the severity and level of SCI could be established from a brief neurological assessment capable of being used in an emergency setting. A brief assessment called the SPinal Emergency Evaluation of Deficits (SPEED) was developed and retrospectively evaluated in a cohort of 118 patients with SCI. Foot motor and sensory function was used to indicate injury severity. C3 dermatome sensation, handgrip strength and location of spinal pain were used to indicate the level of injury. With regard to injury severity, a high proportion of patients (94%) with no foot movement at the time of injury were initially diagnosed as motor complete (American Spinal Injury Association Impairment Scale [AIS] grade A-B), whereas all patients with foot movement were identified as motor incomplete (AIS grade C-D). This was reflected by a good correlation (rs = 0.79) and agreement (κ = 0.85) between the SPEED motor score and the acute hospital assessment. With respect to injury level, the majority of cases with cervical SCI (92%) had no or weak handgrip at the time of paramedic assessment, whereas all cases with thoracolumbar SCI had a strong handgrip. The location of spinal pain was also in accordance with the level of spinal injury. The SPEED assessment appears capable of accurately determining the severity and level of cervical SCI in the first hours post-injury. A neurological assessment that can be performed rapidly after injury is important for clinical trials of early therapy and to identify patients most likely to benefit from intervention.

Retrospective cohort. Pneumonia is the dominant complication following traumatic spinal cord injury (SCI) and profoundly impacts morbidity by prolonging length of stay and worsening neurological outcome. The aims of this study were to determine the key predictors of clinically important pneumonia (CIP); and to examine the impact of CIP on resource utilisation in critically ill acute traumatic SCI individuals between 2010 and 2015. Alfred and Austin Hospitals (Melbourne, Australia). Data were extracted from the medical records of 93 cases of acute traumatic SCI resulting in ISNCSCI C3–L1 level of injury requiring admission to the intensive care unit and aged between 15 and 70 years. Patients with life-threatening injuries, not requiring spinal surgery, palliated within 7 days of injury, diagnosis of traumatic central cord syndrome or with poor general health, were excluded. A total of 33 episodes of CIP were observed. Median time to CIP diagnosis was 65 h (IQR: 42–93) and median time to spinal surgery was 22 h (IQR: 12–32). Four key predictors were identified; male gender (OR: 18.3, CI: 1.9–174.9, p = 0.001), motor complete injury (OR: 10.1, CI: 1.1–92.1, p = 0.011), presence of chest trauma (OR: 4.5, CI: 1.4–14.4, p = 0.007) and delayed intubation (HR: 6.8, CI: 1.6–28.6, p = 0.009). This study identifies four key predictors involved in elevated pneumonia risk; male gender, motor complete injury, presence of chest trauma and delayed intubation, enabling the future synthesis of a pneumonia prediction tool for use in the acute postinjury period.

Focus Group.To develop a unified, regional spinal cord injury (SCI) research strategy for Australia and New Zealand.Australia.A 1-day structured stakeholder dialogue was convened in 2013 in Melbourne, Australia, by the National Trauma Research Institute in collaboration with the SCI Network of Australia and New Zealand. Twenty-three experts participated, representing local and international research, clinical, consumer, advocacy, government policy and funding perspectives. Preparatory work synthesised evidence and articulated draft principles and options as a starting point for discussion.A regional SCI research strategy was proposed, whose objectives can be summarised under four themes. (1) Collaborative networks and strategic partnerships to increase efficiency, reduce duplication, build capacity and optimise research funding. (2) Research priority setting and coordination to manage competing studies. (3) Mechanisms for greater consumer engagement in research. (4) Resources and infrastructure to further develop SCI data registries, evaluate research translation and assess alignment of research strategy with stakeholder interests. These are consistent with contemporary international SCI research strategy development activities.This first step in a regional SCI research strategy has articulated objectives for further development by the wider SCI research community. The initiative has also reinforced the importance of coordinated, collective action in optimising outcomes following SCI.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: The aims of this study were to (1) determine the timing of surgery for traumatic thoracolumbar spinal cord injury (TLSCI) between 2010 and 2014 and (2) identify major delays in the process of care from accident scene to surgery. SUMMARY OF BACKGROUND DATA: Early spinal surgery may promote neurological recovery and reduce acute complications after TLSCI; however, it is difficult to achieve due to logistical issues and the frequent presence of other nonlife-threatening injuries. METHODS: Data were extracted from the medical records of 46 cases of acute traumatic TLSCI (AIS level T1-L1) aged between 15 and 70 years. Patients with life-threatening injuries, not requiring spinal surgery or with poor general health, were excluded. RESULTS: The median time to surgery was 27 hours [interquartile range (IQR): 20-43 hours] and improved from 27 hours in 2010 to 22 hours in 2014. Cases admitted via a pre-surgical hospital had a longer median time to surgery than direct surgical hospital admissions (28 vs. 24 hours, respectively). The median time from completion of radiological investigations to surgery was 18 hours, suggesting that theater access and organization of a surgical team were the major factors contributing to surgical delay. Number of vertebral levels fractured (≥5) and upper thoracic level of injury (T1-8) were also found to be associated with surgical delay. CONCLUSION: Earlier spinal surgery in TLSCI would be facilitated by direct surgical hospital admission and improved access to the operating theater and surgical teams. LEVEL OF EVIDENCE: 3.

Most cases of human spinal cord injury (SCI) are accompanied by continuing cord compression. Experimentally, compression results in rapid neurological decline over hours, suggesting a rise in intracanal pressure local to the site of injury. The aim of this study was to measure the rise in local intracanal pressure accompanying progressive canal occlusion and to determine the relationship between raised intracanal pressure and neurological outcome. We also aimed to establish whether hypothermia was able to reduce raised intracanal pressure. We demonstrate that, following SCI in F344 rats, local intracanal pressure remains near normal until canal occlusion exceeds 30% of diameter, whereupon a rapid increase in pressure occurs. Intracanal pressure appears to be an important determinant of neurological recovery, with poor long-term behavioural and histological outcomes in animals subject to 8 h of 45% canal occlusion, in which intracanal pressure is significantly elevated. In contrast, good neurological recovery occurs in animals with near normal intracanal pressure (animals undergoing 8 h of 30% canal occlusion or those undergoing immediate decompression). We further demonstrate that hypothermia is an effective therapy to control raised intracanal pressure, rapidly reducing elevated intracanal pressure accompanying critical (45%) canal occlusion to near normal. Overall these data indicate that following SCI only limited canal narrowing is tolerated before local intracanal pressure rapidly rises, inducing a sharp decline in neurological outcome. Raised intracanal pressure can be controlled with hypothermia, which may be a useful therapy to emergently decompress the spinal cord prior to surgical decompression.

Human spinal cord injury (SCI) is usually accompanied by persistent cord compression. Experimental data demonstrate that compression of the traumatized cord results in rapid neurological decline over hours. Undertaking decompression in humans within this time frame has proved impractical, with the time to surgery in studies of urgent decompression averaging between 10 and 24 h. There is, therefore, an important need for a therapy to prevent the neurological deterioration of patients prior to decompressive surgery. The aim of this study was to determine if hypothermia prevents compressive SCI, thereby limiting neurological decline. Rats were subjected to a moderate mid-thoracic SCI and spacers were inserted to compress the spinal cord by 45%. Decompression, by removal of the spacer, was performed immediately, and at 2 or 8 h post-injury. Hypothermia (33 degrees C) was commenced in half the animals at 30 mins post-injury and maintained for 7.5 h, with the other half remaining normothermic (37.3 degrees C). Motor recovery was assessed weekly, and the volume and area of tissue damage determined at the end of the 8-week study period. The results demonstrate that hypothermia significantly improves the behavioral and histological outcome of animals undergoing 8 h of compressive injury (the primary outcome measure). The hypothermia-treated group regained weight-supported locomotion (Basso-Beattie-Bresnahan [BBB] locomotor assessment score 9.5 +/- 0.9), while the normothermic group remained severely paraparetic (BBB score 5.3 +/- 0.6; por= 0.0005). Hypothermia significantly increased the volume and area of healthy tissue in the peri-injury region, as well as the volume of preserved white and grey matter. Overall, the data suggest that hypothermia may be a useful bridging therapy to prevent neurological decline prior to decompressive surgery.

Introduction: Leptomeningeal rheumatoid nodules are a rare condition. This case demonstrates the unique presentation and diagnostic workup for the distinctive condition and highlights the difficulties surrounding therapeutics. Case Presentation: A 67 year old woman presented with recurrent transient ischaemic attack-like episodes over a 2 year period. Nodular enhancing leptomeningeal changes were detected on MRI and consistent with meningeal rheumatoid nodules on biopsy. The patient’s nodular disease continued to progress and regress clinically and radiologically irrespective of disease modifying agents and peripheral and serological rheumatoid arthritis control. Conclusions: This patient’s unique presentation and diagnostic work-up is discussed alongside the dilemma of therapeutic management of meningeal rheumatoid nodules.

We report a 28-year-old woman who presented with a partial Brown-Sequard syndrome 18 months after a fall from a horse. Investigation revealed the cause of her symptoms to be a spinal cord herniation at the level of T6. A review of previously reported cases of posttraumatic spinal cord herniation was undertaken. Six of the cases reported have clear evidence of injury at the site of subsequent herniation; the remaining five cases may be related to trauma or may be spontaneous spinal cord herniation, with an unrelated history of trauma.

In Parkinson's disease (PD), dopaminergic input to the caudate nucleus and a band of putaminal tissue abutting the external globus pallidus seems well preserved on immunohistochemical staining for the dopamine transporter. Counting of dopaminergic terminals showed that terminal density in these regions in PD was the same as that in controls, which indicates that input is truly preserved and not a consequence of a compensatory upregulation of metabolism in a reduced pool of surviving terminals. When the branching pattern of dopaminergic axons coursing through the globus pallidus was examined, we found no evidence for increased axonal sprouting in PD that might have contributed to preservation of dopaminergic input to the putamen or caudate nucleus. Although terminal counting indicated that anatomic input was preserved to parts of the striatum, dopamine uptake site density in these regions was reduced significantly. This suggests that the impact of disease in these areas is more profound than was thought previously.

A 67-year-old woman presented with recurrent transient ischaemic attack-like episodes over a 2 year period. Nodular enhancing leptomeningeal changes were detected on MRI and were consistent with meningeal rheumatoid nodules on biopsy. The patient's nodular disease continued to progress and regress clinically and radiologically irrespective of disease modifying agents and peripheral and serological rheumatoid arthritis control. This patient's unique presentation and diagnostic work-up is discussed alongside the dilemma of therapeutic management of meningeal rheumatoid nodules.

Peripheral nerve preconditioning lesions have been shown to consistently enhance sensory nerve regeneration in the injured spinal cord.The aim of this study was to determine if the rat motor cortex could be preconditioned through the implantation of Schwann cells (SC), thereby stimulating sprouting and regeneration of the corticospinal tract (CST).Schwann cells (cultured in vitro) were injected into the motor cortex and seven days post-surgery rats underwent a dorsal spinal hemisection injury. Eight weeks following spinal injury animals were perfused and the CST visualised by Avidin-peroxidase histochemistry for dextran-biotin.Results demonstrate substantially enhanced CST collateral sprouting in both the rostral grey and white matter of the injured spinal cord in animals with SC implanted into the motor cortex compared to control animals with and without cortical vehicle injections. Corticospinal tract peri-wound regenerative sprouting was also enhanced in animals implanted with cortical SC compared to controls, however, only a small degree of CST axonal regeneration was present in the grey matter beneath the injury site. In all groups, CST peri-lesional regenerative sprouting occurred in close proximity to macrophages. Complicated and intimate relationships between CST fibres and these cells were evident.Overall, our data demonstrates that preconditioning the motor cortex with SC prior to spinal injury results in greatly enhanced CST sprouting and that CST peri-wound sprouting takes place in juxtaposition to macrophages.

Animal models of ischemic stroke often neglect comorbidities common in patients. This study shows the feasibility of inducing stroke by 2 h of thread occlusion of the middle cerebral artery in aged (56 week old) spontaneously hypertensive rats (SHRs) with both acute (2 weeks) and chronic (36 weeks) diabetes. After modifying the streptozotocin dosing regimen to ensure that old SHRs survived the induction of diabetes, few died after induction of stroke. Induction of stroke is feasible in rats with multiple comorbidities. Inclusion of such comorbid animals may improve translation from the research laboratory to the clinic.

Inflammation in the CNS predominantly involves microglia and macrophages, and is believed to be a significant cause of secondary injury following trauma. This study compares the microglial and macrophage response in the rat brain and spinal cord following discrete mechanical injury to better appreciate the degree to which these cells could contribute to secondary damage in these areas. We find that, 1 week after injury, the microglial and macrophage response is significantly greater in the spinal cord compared to the brain. This is the case for injuries to both gray and white matter. In addition, we observed a greater inflammatory response in white matter compared to gray matter within both the brain and spinal cord. Because activated microglia and macrophages appear to be effectors of secondary damage, a greater degree of inflammation in the spinal cord is likely to result in more extensive secondary damage. Tissue saving strategies utilizing anti-inflammatory treatments may therefore be more useful in traumatic spinal cord than brain injury.

Traumatic injury to the CNS results in peri-wound sprouting without significant axonal growth beyond the lesion edge. We have previously demonstrated that dopaminergic sprouting in the injured striatum follows an increasing gradient of BDNF and GDNF expression, with sprouting ceasing at the point of maximal factor expression. Progressively more complicated associations of sprouting fibers with increasingly activated microglia and macrophages suggest these factors are localized to the cell surface. To establish whether an increased concentration of immobilized BDNF and GDNF could stimulate axonal growth beyond the lesion edge, both factors were covalently attached to 10 microm polycarbonate microspheres. These spheres were implanted into the site of striatal injury 1 week after lesioning. A profusion of axons grew from the region of the lesion edge across the surface of the spheres. Some axons traversed the entire site of injury. Ultrastructural examination demonstrated the juxtaposition of regenerating axons to the surface of implanted spheres. CSPG immunostaining demonstrated that, in animals implanted with neurotrophin-microspheres, axonal growth was induced beyond the area of maximal CSPG reactivity. Surprisingly however, CSPG production at the wound edge was greater in control animals than those implanted with neurotrophin-microspheres. Overall, we show that axonal growth can be encouraged beyond the wound edge by an elevated concentration of immobilized trophic factors. This growth occurs despite the presence of inhibitory CSPGs at the lesion edge. Axonal growth appears to be stimulated mainly via the direct effects of neurotrophins. However, there also appears to be an indirect mechanism whereby neurotrophins reduce the synthesis of CSPG at the wound edge, making the peri-wound environment more permissive.

The mechanism of action for lumbar blood patches affecting a therapeutic response in a proximal cerebrospinal fluid (CSF) leak is thought to be via a tamponade effect. However, our case study reveals that blood products reach and pool at the site of a proximal CSF leak in the cervical spine – therefore we hypothesise that the therapeutic response results from a combination of a tamponade effect and blood products forming a localised clot in the proximal cervical region. We present a 41-year-old woman with a 12 month history of headache from postural hypotension. The patient’s general practitioner ordered a CT scan of the brain and lumbar spine as part of a workup which revealed that the patient had a cervical spine CSF leak. Subsequent MRI confirmed the CSF leak and intracranial hypotension. A 25 ml epidural blood patch was performed in the lumbar region together with conservative measures including a period of strict bed rest for days with increased hydration and caffeine intake. The patient reported an immediate symptomatic improvement following blood patching with a reduction in headaches. Subsequent imaging revealed resolution of the intracranial hypotension. We followed up the patient with serial MRI scans. These revealed blood reaching and pooling around the site of the CSF leak in the cervical spine. The current case report demonstrates that a lumbar epidural injection of blood reaches and pools around a CSF leak as far proximally as the cervical region. This supports the “plug” theory as the mechanism for persistent symptom resolution. However, the mechanism of immediate symptomatic improvement may still involve a tamponade effect. This two stage process appears to be the best explanation for the therapeutic response obtained from epidural blood patching on the basis of the available clinical, imaging and experimental data.