Magnetic resonance imaging findings in dogs with traumatic intervertebral disk extrusion with or without spinal cord compression: 31 cases (2006-2010)

OBJECTIVE To determine the prevalence of spinal cord compression subsequent to traumatic intervertebral disk (IVD) extrusion in dogs, characterize factors associated with spinal cord compression in dogs with traumatic IVD extrusion, and evaluate the outcomes of dogs with traumatic IVD extrusion with or without spinal cord compression. DESIGN Retrospective case series. ANIMALS 31 dogs with traumatic IVD extrusion. PROCEDURES Medical records and MRI findings were reviewed for dogs with a history of trauma to the spinal region. Dogs were included in the study if a neurologic examination and MRI were performed and there was a description of clinical signs and MRI findings including identification of the spinal cord segment affected by IVD extrusion, presence or absence of spinal cord compression, treatment, and outcome available for review. RESULTS 31 of 50 (62%) dogs had traumatic IVD extrusions without any other detectable vertebral lesions; 9 (29%) and 22 (71%) of those 31 dogs did and did not have spinal cord compression, respectively. Dogs with spinal cord compression were significantly older and more likely to be chondrodystrophic and have evidence of generalized IVD degeneration, compared with dogs without spinal cord compression. The outcome for dogs with spinal cord compression was similar to that for dogs without spinal cord compression. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated traumatic IVD extrusion was common and should be considered as a differential diagnosis for dogs with trauma to the spinal region, and spinal cord compression should be evaluated, especially in older or chondrodystrophic dogs.

Malignant spinal cord compression: prospective study of delays in referral and treatment

Objectives: To examine the delay in presentation, diagnosis, and treatment of malignant spinal cord compression and to define the effect of this delay on motor and bladder function at the time of treatment.

Characterization of the glial scar tissue in a murine model of spinal cord compression, with focus on hyaluronan

Spinal cord injury (SCI) is a devastating neurological disorder that affects thousands of people each year. Although in recent decades significant progress has been made in relation to understanding the molecular and cellular events underlying the nervous damage, spinal cord injury is still a highly disabling condition for which there is no curative therapy. People affected by spinal cord injuries manifested dysfunction or loss, temporary or permanent, of motor, sensory and / or autonomic functions depending on the spinal lesion damaged. Currently, the incidence rate of this type of injury is approximately 15-40 cases per million people worldwide. At the origin of these lesions are: road accidents, falls, interpersonal violence and the practice of sports. In this work we placed the hypothesis that HA is one of the component of the scar tissue formed after a compressive SCI, that it is likely synthetised by the perilesional glial cells and that it might support the permeation of the glial scar during the late phase of SCI. Nowadays, much focus is drawn on the recovery of CNS function, made impossible after SCI due to the high content of sulfated proteoglycans in the extracellular matrix. Counterbalancing the ratio between these proteoglycans and hyaluronic acid could be one of the experimental therapy to re-permeate the glial scar tissue formed after SCI, making possible axonal regrowth and functional recovery. Therefore, we established a model of spinal cord compression in mice and studied the glial scar tissue, particularly through the characterization of the expression of enzymes related to the metabolism of HA and the subsequent concentration thereof at different distances of the lesion epicenter. Our results show that the lesion induced in mice shows results similar to those produced in human lesions, in terms of histologic similarities and behavioral results. but these animals demonstrate an impressive spontaneous reorganization mechanism of the spinal cord tissue that occurs after injury and allows for partial recovery of the functions of the CNS. As regards the study of the glial scar, changes were recorded at the level of mRNA expression of enzymes metabolizing HA i.e., after injury there was a decreased expression of HA synthases 1-2 (HAS 1-2) and an increase of the expression HAS3 synthase mRNA, as well as the enzymes responsible for the HA catabolism, HYAL 1-2. But the amount of HA measured through the ELISA test was found unchanged after injury, it is not possible to explain this fact only with the change of expression of enzymes. At two weeks and in response to SCI, we found synthesized HA by reactive astrocytes and probably by others like microglial cells as it was advanced by the HA/GFAP+ and HA/IBA1+ cells co-location.

The prevalence and phenotype of activated microglia/macrophages within the spinal cord of the hyperostotic mouse (twy/twy) changes in response to chronic progressive spinalcord compression:implications for human cervical compressive myelopathy

Background:Cervical compressive myelopathy, e.g. due to spondylosis or ossification of the posterior longitudinal ligament is a common cause of spinal cord dysfunction. Although human pathological studies have reported neuronal loss and demyelination in the chronically compressed spinal cord, little is known about the mechanisms involved. In particular, the neuroinflammatory processes that are thought to underlie the condition are poorly understood. The present study assessed the localized prevalence of activated M1 and M2 microglia/macrophages in twy/twy mice that develop spontaneous cervical spinal cord compression, as a model of human disease.Methods:Inflammatory cells and cytokines were assessed in compressed lesions of the spinal cords in 12-, 18- and 24-weeks old twy/twy mice by immunohistochemical, immunoblot and flow cytometric analysis. Computed tomography and standard histology confirmed a progressive spinal cord compression through the spontaneously development of an impinging calcified mass.Results:The prevalence of CD11b-positive cells, in the compressed spinal cord increased over time with a concurrent decrease in neurons. The CD11b-positive cell population was initially formed of arginase-1- and CD206-positive M2 microglia/macrophages, which later shifted towards iNOS- and CD16/32-positive M1 microglia/macrophages. There was a transient increase in levels of T helper 2 (Th2) cytokines at 18 weeks, whereas levels of Th1 cytokines as well as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and macrophage antigen (Mac) -2 progressively increased.Conclusions:Spinal cord compression was associated with a temporal M2 microglia/macrophage response, which may act as a possible repair or neuroprotective mechanism. However, the persistence of the neural insult also associated with persistent expression of Th1 cytokines and increased prevalence of activated M1 microglia/macrophages, which may lead to neuronal loss and demyelination despite the presence of neurotrophic factors. This understanding of the aetiopathology of chronic spinal cord compression is of importance in the development of new treatment targets in human disease. © 2013 Hirai et al.

Influence of Durotomy on Laser-Doppler Measurement of Spinal Cord Blood Flow in Chondrodystrophic Dogs with Thoracolumbar Disk Extrusion

OBJECTIVES: To assess influence of durotomy on spinal cord blood flow (SCBF) in chondrodystrophic dogs with thoracolumbar disk extrusion. STUDY DESIGN: Prospective cohort study. ANIMALS: Chondrodystrophic dogs with thoracolumbar disk extrusion (n = 11). METHODS: Diagnosis was based on neurologic signs, magnetic resonance imaging (MRI) findings, and surgical confirmation. Regional SCBF was measured 3 times intraoperatively by laser-Doppler flowmetry: (1) before surgical decompression; (2) immediately after decompression by hemilaminectomy-durotomy; and (3) after 15 minutes of lesion lavage. A standardized hemilaminectomy and durotomy performed by the same neurosurgeon, was used to minimize factors that could influence measurement readings. RESULTS: A significant increase in intraoperative SCBF was found immediately after spinal cord decompression and durotomy in dogs but SCBF returned to previous levels or lower after 15 minutes of lavage. Changes in SCBF were not associated with duration of clinical signs; neurologic status, degree of spinal cord compression, or signal intensity changes as assessed by MRI. CONCLUSION: Durotomy does not increase SCBF in dogs with disk extrusion associated spinal cord compression.

Laser-Doppler measurements of spinal cord blood flow changes during hemilaminectomy in chondrodystrophic dogs with disk extrusion

OBJECTIVES: (1) To assess spinal cord blood flow (SCBF) during surgical treatment of disk extrusion in dogs and (2) to investigate associations between SCBF, clinical signs, presurgical MRI images, and 24-hour surgical outcome. STUDY DESIGN: Cohort study. ANIMALS: Chondrodystrophic dogs with thoracolumbar disk extrusion (n=12). METHODS: Diagnosis was based on clinical signs and MRI findings, and confirmed at surgery. Regional SCBF was measured intraoperatively by laser-Doppler flowmetry before, immediately after surgical spinal cord decompression, and after 15 minutes of lavaging the lesion. Care was taken to ensure a standardized surgical procedure to minimize factors that could influence measurement readings. RESULTS: A significant increase in intraoperative SCBF was found in all dogs (Wilcoxon's signed-rank test; P=.05) immediately after spinal cord decompression and after 15 minutes. Changes in SCBF were not associated with duration of clinical signs; initial or 24-hour neurologic status; or degree of spinal cord compression assessed by MRI. CONCLUSION: SCBF increases immediately after spinal cord decompression in dogs with disk herniation; however, increased SCBF was not associated with a diminished 24-hour neurologic status. CLINICAL RELEVANCE: An increase in SCBF does not appear to be either associated with the degree of spinal cord compression or of a magnitude sufficient to outweigh the benefit of surgical decompression by resulting in clinically relevant changes in 24-hour outcome.

CM101-mediated recovery of walking ability in adult mice paralyzed by spinal cord injury

CM101, an antiangiogenic polysaccharide derived from group B streptococcus, was administered by i.v. injection 1 hr post-spinal-cord crush injury in an effort to prevent inflammatory angiogenesis and gliosis (scarring) in a mouse model. We postulated that gliosis would sterically prevent the reestablishment of neuronal connectivity; thus, treatment with CM101 was repeated every other day for five more infusions for the purpose of facilitating regeneration of neuronal function. Twenty-five of 26 mice treated with CM101 survived 28 days after surgery, and 24 of 26 recovered walking ability within 2–12 days. Only 6 of 14 mice in the control groups survived 24 hr after spinal cord injury, and none recovered function in paralyzed limbs. MRI analysis of injured untreated and treated animals showed that CM101 reduced the area of damage at the site of spinal cord compression, which was corroborated by histological analysis of spinal cord sections from treated and control animals. Electrophysiologic measurements on isolated central nervous system and neurons in culture showed that CM101 protected axons from Wallerian degeneration; reversed γ-aminobutyrate-mediated depolarization occurring in traumatized neurons; and improved recovery of neuronal conductivity of isolated central nervous system in culture.

Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial

BACKGROUND: Bone metastases frequently cause skeletal events in patients with metastatic castration-resistant prostate cancer. Radium-223 dichloride (radium-223) selectively targets bone metastases with high-energy, short-range α-particles. We assessed the effect of radium-223 compared with placebo in patients with castration-resistant prostate cancer and bone metastases.

METHODS: In this phase 3, double-blind, randomised ALSYMPCA trial, we enrolled patients who had symptomatic castration-resistant prostate cancer with two or more bone metastases and no known visceral metastases, who were receiving best standard of care, and had previously either received or were unsuitable for docetaxel. Patients were stratified by previous docetaxel use, baseline total alkaline phosphatase level, and current bisphosphonate use, then randomly assigned (2:1) to receive either six intravenous injections of radium-223 (50 kBq/kg) or matching placebo; one injection was given every 4 weeks. Randomisation was done with an interactive voice response system, taking into account trial stratification factors. Participants and investigators were masked to treatment assignment. The primary endpoint was overall survival, which has been reported previously. Here we report on time to first symptomatic skeletal event, defined as the use of external beam radiation to relieve bone pain, or occurrence of a new symptomatic pathological fracture (vertebral or non-verterbal), or occurence of spinal cord compression, or tumour-related orthopeadic surgical intervention. All events were required to be clinically apparent and were not assessed by periodic radiological review. Statistical analyses of symptomatic skeletal events were based on the intention-to-treat population. The study has been completed and is registered with ClinicalTrials.gov, number NCT00699751.

FINDINGS: Between June 12, 2008, and Feb 1, 2011, 921 patients were enrolled, of whom 614 (67%) were randomly assigned to receive radium-223 and 307 (33%) placebo. Symptomatic skeletal events occurred in 202 (33%) of 614 patients in the radium-223 group and 116 (38%) of 307 patients in the placebo group. Time to first symptomatic skeletal event was longer with radium-223 than with placebo (median 15·6 months [95% CI 13·5-18·0] vs 9·8 months [7·3-23·7]; hazard ratio [HR]=0·66, 95% CI 0·52-0·83; p=0·00037). The risks of external beam radiation therapy for bone pain (HR 0·67, 95% CI 0·53-0·85) and spinal cord compression (HR=0·52, 95% CI 0·29-0·93) were reduced with radium-233 compared with placebo. Radium-223 treatment did not seem to significantly reduce the risk of symptomatic pathological bone fracture (HR 0·62, 95% CI 0·35-1·09), or the need for tumour-related orthopaedic surgical intervention (HR 0·72, 95% CI 0·28-1·82).

INTERPRETATION: Radium-223 should be considered as a treatment option for patients with castration-resistant prostate cancer and symptomatic bone metastases.

FUNDING: Algeta and Bayer HealthCare Pharmaceuticals.

Chondromas of the spine: report of two cases and review of the literature.

We report two cases of vertebral chondroma presenting with spinal cord compression. In one case there was ultimate malignant transformation.

Advances in drug design based on the amino acid approach: Taurine analogues for the treatment of CNS diseases

Amino acids are well known to be an important class of compounds for the maintenance of body homeostasis and their deficit, even for the polar neuroactive aminoacids, can be controlled by supplementation. However, for the amino acid taurine (2-aminoethanesulfonic acid) this is not true. Due its special physicochemical properties, taurine is unable to cross the blood-brain barrier. In addition of injured taurine transport systems under pathological conditions, CNS supplementation of taurine is almost null. Taurine is a potent antioxidant and anti-inflammatory semi-essential amino acid extensively involved in neurological activities, acting as neurotrophic factor, binding to GABA A/glycine receptors and blocking the excitotoxicity glutamate-induced pathway leading to be a neuroprotective effect and neuromodulation. Taurine deficits have been implicated in several CNS diseases, such as Alzheimer's, Parkinson's, epilepsy and in the damage of retinal neurons. This review describes the CNS physiological functions of taurine and the development of new derivatives based on its structure useful in CNS disease treatment.&; 2012 by the authors; licensee MDPI, Basel, Switzerland.

Resistência mecânica e alterações radiográficas na distração e estabilização intervertebral usando plug de poliuretana de mamona ou polimetilmetacrilato

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Partial lateral corpectomy associated with pediculectomy to treat extradural chondroma in a dog: technique description

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)