The dura causes spinal cord compression after spinal cord injury.

MR scans from 65 patients with traumatic spinal cord injury were analysed; on admission 95% had evidence of cord compression - in 26% due to the dura, and in the remaining 74% due to extradural factors. Compression due to dural factors resolved with a half-life of 8.7 days. These findings suggest that bony decompression alone may not relieve spinal cord compression in the quarter of patients in whom dural factors are significant.

Interobserver agreement of magnetic resonance imaging signs of osteomyelitis in pelvic pressure ulcers in patients with spinal cord injury.

OBJECTIVE: To examine the interobserver reliability of magnetic resonance imaging (MRI) signs of osteomyelitis in complex chronic pressure ulcers in patients with spinal cord injury (SCI). DESIGN: Retrospective review study. SETTING: Specialist SCI rehabilitation center. PARTICIPANTS: Adult patients with SCI and pressure ulceration investigated with MRI. INTERVENTIONS: Analysis of MRI examinations and clinical records collected over a 4-year period. Images were independently assessed by 2 experienced radiologists for osteomyelitis based on assigned predictive indicators including cortical bone erosion, soft tissue edema, deep collections, heterotopic new bone, hip effusion, and abnormal signal change of the marrow. MAIN OUTCOME MEASURES: Interobserver agreement for indicative MRI signs of osteomyelitis in complex pressure ulcers. RESULTS: Thirty-seven patients underwent 41 MRI scans. Concordance for marrow edema was 71% on both short tau inversion recovery and T1-weighted sequences, and for cortical erosion was 85%. CONCLUSIONS: For the assessment of pelvic osteomyelitis related to pressure ulcers, the T1-weighted MRI signal for marrow edema and cortical erosion has strong interobserver agreement.

Diagnosing and managing spinal injury in patients with ankylosing spondylitis.

BACKGROUND: Individuals with ankylosing spondylitis are at an increased risk of vertebral fractures. These are often unstable, leading to primary and secondary neurological injury and conferring high levels of morbidity and mortality. Fractures in these patients can occur after minimal trauma and are easily missed, with potentially disastrous consequences. OBJECTIVES: To educate health professionals who may be involved in the initial assessment and management of ankylosing spondylitis patients with possible spinal injuries, despite not being spinal specialists. CASE REPORTS: We present three cases from our own hospital, which illustrate the pitfalls associated with traumatic spinal injury in ankylosing spondylitis. Case 1 shows why delayed presentation of spinal injury is common, as well as demonstrating the need for multiple imaging modalities in some patients. Case 2 is an example of primary neurological injury in this patient group, and case 3 highlights the risk of secondary neurological injury, as well as the effect of multiple comorbidities on patient outcomes. CONCLUSIONS: It is important that staff in the Emergency Department have an understanding of the extreme caution that is needed in the management of possible spinal injuries in patients with or suspected of having ankylosing spondylitis.

Review: indications for interventional radiology in the management of patients with spinal cord injuries.

OBJECTIVES: To outline a range of minimally invasive image-guided procedures that benefit spinal cord-injured patients and may expedite clinical care. STUDY DESIGN: Pictorial review. RESULTS/CONCLUSIONS: Image-guided procedures have made a significant impact in medical management in many specialties. These techniques continue to evolve rapidly and afford opportunities to reduce patient morbidity and in-patient length of stay.

Magnetic resonance imaging of pressure sores in spinal cord injured patients: accuracy in predicting osteomyelitis.

OBJECTIVE: Identify key magnetic resonance imaging (MRI) features that have a significant correlation with osteomyelitis of pressure ulcers in spinal injury patients. DESIGN: Retrospective review study. PARTICIPANTS: Adult patients admitted to the National Spinal Injuries Centre with spinal cord injury (SCI) and signs of pressure ulceration investigated with MRI. METHODS: Analysis of MRI examinations and clinical records collected over a 4-year period. Images were independently assessed by 2 experienced radiologists for osteomyelitis based on assigned predictive indicators including cortical bone erosion, soft tissue edema, deep collections, heterotopic new bone, hip effusion, and abnormal signal change of the marrow. RESULTS: Thirty-seven patients underwent 41 MRI scans. The prevalence of osteomyelitis was highly correlated with cortical bone erosion (r = 0.84) and abnormal bone marrow changes on T1-weighted images (r = 0.82).

Observations on the function of nuclear factor kappa B (NF-kappaB) in the survival of adult primary sensory neurons after nerve injury.

Peripheral nerve transections cause much more neuronal death in embryonic and neonatal dorsal root ganglia (DRG) than in adult DRG. Here we used transgenic approaches to examine the hypothesis that NF-kappaB is an important intrinsic factor of adult DRG neurons for their in vivo capacity to survive after nerve injury. We generated transgenic mice expressing the NF-kappaB super-inhibitor (IkappaBalpha-SI), a multi-mutant form of IkappaBalpha, specifically in adult neurons. Adult DRG neurons in these transgenic animals are not abnormally susceptible to apoptosis after peripheral nerve injury, although there is a significant inhibition in the ability of NF-kappaB to translocate into their nucleus. We investigated the observed lack of NF-kappaB neuroprotective function at the level of NF-kappaB transcriptional activity using transgenic NF-kappaB/LacZ reporter mice. We show that the expression of the NF-kappaB reporter transgene is restricted in naïve and injured DRG neurons. However, NF-kappaB transcriptional activity in adult DRG neurons is evident upon exposure to Trichostatin A (TSA) which is a specific inhibitor of histone deacetylases. Taken together our results illustrate that the functions of NF-kappaB are limited in adult primary sensory neurons due to a transcriptional repression mechanism mediated by histone deacetylases, and that intrinsic neuroprotective factors other than NF-kappaB are responsible for the resistance of adult DRG neurons to apoptosis in response to nerve injury.

Prediction of novel isoforms of the mouse Mpv17l protein.

The Mpv17l protein has two isoforms, M-LPL and M-LPS, which both regulate the production of reactive oxygen species (ROS) and protect against mitochondrial oxidative stress and apoptosis. M-LPL is ubiquitously expressed, while M-LPS is expressed mostly in the kidney of aged animals. We identified a variety of transcripts of the Mpv17l gene that could encode novel isoforms by mapping expressed sequence tags on the mouse M-LP genomic locus. We analysed the expression and evolutionary conservation of a novel Mpv17l transcript (mpv17l-002) that is predicted to encode a new protein, termed M-LP2. The isoform M-LP2 has the full length of M-LPS plus six amino acids at the end of its amino terminus, which could be encoded by an alternative 5'-flanking sequence. We show that the mRNA of M-LP2 has a different pattern of expression than the mRNA of M-LPS, and sequences of both transcripts are conserved in the rodent genome; however, neither of these isoforms is detected in the human genome. These observations suggest that the functions of certain M-LP isoforms are tissue- and species-specific, implying that their potential involvement in ROS metabolism may be redundant or may be complemented by other members of the Mpv17 family.

Fatty acid methyl esters are detectable in the plasma and their presence correlates with liver dysfunction.

BACKGROUND: Methanol is a component of certain alcoholic beverages and is also an endogenously formed product. On this basis, we have proposed that methanol may promote synthesis of fatty acid methyl esters (FAMEs) in the same way that ethanol promotes fatty acid ethyl ester (FAEE) synthesis. We tested the hypothesis that FAMEs appear in the blood after ethanol intake. METHODS: Patient plasma samples obtained from our laboratory (n=78) were grouped according to blood ethanol concentrations (intoxicated, blood ethanol >800 mg/l) and non-intoxicated. These samples were further subdivided into groups based on whether the patient had normal or abnormal liver function tests (abnormal, defined as > or =1 abnormality of plasma alanine and aspartate aminotransferase, albumin, total bilirubin, and alkaline phosphatase). A separate set of plasma samples were also divided into normal and abnormal groups based on pancreatic function tests (amylase and lipase). There were no patients with detectable ethanol in this group. Patients with abnormalities in pancreatic function tests were included upon recognition of endogenously produced FAMEs by patients with liver function test abnormalities. FAMEs were extracted from plasma and individual species of FAMEs quantified by gas chromatography-mass spectrometry (GC/MS). RESULTS: Increased concentrations of FAME were found in patient samples with evidence of liver dysfunction, regardless of whether or not they were intoxicated (n=21, p=0.01). No significant differences in plasma FAME concentrations were found between patients with normal (n=15) versus abnormal pancreatic function tests (n=22, p=0.72). CONCLUSIONS: The presence of FAMEs in human plasma may be related to the existence of liver disease, and not to blood ethanol concentrations or pancreatic dysfunction. The metabolic pathways associated with FAME production in patients with impaired liver function remain to be identified.

Lack of the transcription factor C/EBPδ impairs the intrinsic capacity of peripheral neurons for regeneration.

Adult neurons of the peripheral nervous system (PNS), in contrast to those of the central nervous system, have a remarkable capacity to repair themselves after injury, yet the mechanisms underlying this regenerative propensity of peripheral neurons are far from completely understood. Here we show that the transcription factor CCAAT enhancer binding protein delta (C/EBPδ) is necessary for the efficient axonal regeneration of dorsal root ganglia (DRG) neurons after sciatic nerve crush injury. Loss of C/EBPδ substantially impairs axonal growth in dissociated cultured DRG neurons. In addition, lack of C/EPBδ causes a major reduction in the regenerative response of DRG neurons to a conditioning lesion, which is a well known paradigm of injury that enhances axonal growth due to a transcription-dependent cell body response. C/EBPδ is required for the induction of selected regeneration-associated genes. For example, the expression of SPRR1A (small proline-rich repeat protein 1A) is greatly reduced in DRG neurons of C/EBPδ knockout mice during axonal regeneration compared to those in wild-type mice, while the expression of GAP-43 (growth associated protein-43) and galanin is not affected. Nevertheless, the expected prompt recovery of sciatic nerve function after injury is severely impaired in C/EBPδ knockout mice, having a delay time of approximately 1 month for reaching the full function of recovering wild-type mice, suggesting that a transcription mechanism mediated by C/EBPδ is required for efficient axonal regeneration. Taken together, our results identify C/EBPδ as a crucial component of the transcriptional regulatory machinery which underlies the intrinsic capacity of peripheral neurons for axonal regeneration.

Bioluminescence imaging of the brain response to acute inflammation in living C/EBP reporter mice.

The transcription factor CCAAT enhancer binding protein (C/EBP) is a key regulator of inflammation and immune responses, and recent studies suggest it is involved in inflammatory processes in the nervous system. We generated a transgenic reporter mouse model, carrying the luciferase (luc) gene under the transcriptional control of C/EBP, for visualising C/EBP activity in vivo. Real-time bioluminescence imaging reflecting C/EBP activity was performed in an acute inflammation model, after systemic administration of lipopolysaccharides (LPS), in C/EBP-luc mice. A striking activity of C/EBP was imaged predominantly in the brain of living C/EBP-luc mice in response to LPS, showing for the first time in vivo that C/EBP mediates the brain response to inflammation. Furthermore, dexamethasone, a potent anti-inflammatory agent, diminished the LPS-induced C/EBP activity demonstrating the physiological regulation of bioluminescence intensity in the brain of C/EBP-luc mice. Our results implicate that C/EBP reporter mice have the potential to be a valuable tool for studies on the mechanisms of brain inflammation in vivo and for the noninvasive preclinical evaluation of therapeutic agents targeting neuroinflammatory diseases.