Correlations between severity of clinical signs and histopathological changes in 60 dogs with spinal cord injury associated with acute thoracolumbar intervertebral disc disease

The outcome of spinal surgery in dogs with absent voluntary motor function and nociception following intervertebral disc (IVD) herniation is highly variable, which likely attests to differences in the severity of spinal cord damage. This retrospective study evaluated the extent to which neurological signs correlated with histologically detected spinal cord damage in 60 dogs that were euthanased because of thoracolumbar IVD herniation. Clinical neurological grades correlated significantly with the extent of white matter damage (P<0.001). However, loss of nociception also occurred in 6/31 (19%) dogs with relatively mild histological changes. The duration of clinical signs, Schiff-Sherrington posture, loss of reflexes and pain on spinal palpation were not significantly associated with the severity of spinal cord damage. Although clinical-pathological correlation was generally good, some clinical signs frequently thought to indicate severe cord injury did not always correlate with the degree of cord damage, suggesting functional rather than structural impairment in some cases.

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.

Kinetics of maternally acquired anti-hepatitis A antibodies: prediction of waning based on maternal or cord blood antibody levels

BACKGROUND Timing is critical for efficient hepatitis A vaccination in high endemic areas as high levels of maternal IgG antibodies against the hepatitis A virus (HAV) present in the first year of life may impede the vaccine response. OBJECTIVES To describe the kinetics of the decline of anti-HAV maternal antibodies, and to estimate the time of complete loss of maternal antibodies in infants in León, Nicaragua, a region in which almost all mothers are anti-HAV seropositive. METHODS We collected cord blood samples from 99 healthy newborns together with 49 corresponding maternal blood samples, as well as further blood samples at 2 and 7 months of age. Anti-HAV IgG antibody levels were measured by enzyme immunoassay (EIA). We predicted the time when antibodies would fall below 10 mIU/ml, the presumed lowest level of seroprotection. RESULTS Seroprevalence was 100% at birth (GMC 8392 mIU/ml); maternal and cord blood antibody concentrations were similar. The maternal antibody levels of the infants decreased exponentially with age and the half-life of the maternal antibody was estimated to be 40 days. The relationship between the antibody concentration at birth and time until full waning was described as: critical age (months)=3.355+1.969 × log(10)(Ab-level at birth). The survival model estimated that loss of passive immunity will have occurred in 95% of infants by the age of 13.2 months. CONCLUSIONS Complete waning of maternal anti-HAV antibodies may take until early in the second year of life. The here-derived formula relating maternal or cord blood antibody concentrations to the age at which passive immunity is lost may be used to determine the optimal age of childhood HAV vaccination.

Restoring tactile awareness through the rubber hand illusion in cervical spinal cord injury

BACKGROUND Bodily sensations are an important component of corporeal awareness. Spinal cord injury can leave affected body parts insentient and unmoving, leading to specific disturbances in the mental representation of one's own body and the sense of self. OBJECTIVE Here, we explored how illusions induced by multisensory stimulation influence immediate sensory signals and tactile awareness in patients with spinal cord injuries. METHODS The rubber hand illusion paradigm was applied to 2 patients with chronic and complete spinal cord injury of the sixth cervical spine, with severe somatosensory impairments in 2 of 5 fingers. RESULTS Both patients experienced a strong illusion of ownership of the rubber hand during synchronous, but not asynchronous, stroking. They also, spontaneously reported basic tactile sensations in their previously numb fingers. Tactile awareness from seeing the rubber hand was enhanced by progressively increasing the stimulation duration. CONCLUSIONS Multisensory illusions directly and specifically modulate the reemergence of sensory memories and enhance tactile sensation, despite (or as a result of) prior deafferentation. When sensory inputs are lost, and are later illusorily regained, the brain updates a coherent body image even several years after the body has become permanently unable to feel. This particular example of neural plasticity represents a significant opportunity to strengthen the sense of the self and the feelings of embodiment in patients with spinal cord injury.

Preeclampsia enhances neuroglial marker expression in umbilical cord Wharton's jelly-derived mesenchymal stem cells.

Objective: The aim of the study was to compare the neuroglial phenotype of Wharton's jelly-derived mesenchymal stem cells (WJ-MSC) from pregnancies complicated with preeclampsia and gestational age (GA)-matched controls. Methods: WJ-MSC were isolated from umbilical cords from both groups and analyzed for the cell surface expression of MSC markers and the gene and protein expression of neuroglial markers. Results: All WJ cells were highly positive for the MSC markers CD105, CD90 and CD73, but negative for markers specific for hematopoietic (CD34) and immunological cells (CD45, CD14, CD19 and HLA-DR). WJ-MSC from both groups expressed neuroglial markers (MAP-2, GFAP, MBP, Musashi-1 and Nestin) at the mRNA and protein level. The protein expressions of neuronal (MAP-2) and oligodendrocytic (MBP) markers were significantly increased in WJ-MSC from preeclampsia versus GA-matched controls. Conclusions: WJ-MSC from preeclamptic patients are possibly more committed to neuroglial differentiation through the activation of pathways involved both in the pathophysiology of the disease and in neurogenesis.

Hans Brun: a Swiss pioneer in the surgery of the spinal cord, brain and herniated lumbar disc

INTRODUCTION Toward the end of the nineteenth century, it was Gowers, Horsley and Macewen who first reported successful surgical procedures for the treatment of subdural extramedullary tumors. Following this, Church and Eisendrath as well as Putnam and Warren reported unsuccessful attempts to treat subpial spinal pathologies in their patients. Only at the beginning of the twentieth century did reports of successful interventions of this type accumulate. In the analysis of these case reports, the authors noticed a certain lack of accuracy about the anatomical allocations and descriptions of intra- and extramedullary spinal lesions. From this, the question of who actually carried out the pioneering works in the early twentieth century in the field of surgery of intramedullary pathologies arose. METHODS Analysis of the relevant original publications of Hans Brun and research on the poorly documented information about his life history by personally contacting contemporary relatives. RESULTS The literature analysis showed that the Swiss neurologist Otto Veraguth and surgeon Hans Brun made fundamental contributions to subpial spinal cord surgery at the very beginning of the last century that remain valid today. According to our research, Hans Brun should be remembered as the third surgeon (after von Eiselsberg and Elsberg) who successfully removed an intramedullary lesion in a patient. CONCLUSION Brun should be remembered as an early and successful surgeon in this specialized field. His operative work is described in detail in this article. At the same time, his achievements in the fields of brain and disc herniation surgery are presented.

Neutrophils mediate blood-spinal cord barrier disruption in demyelinating neuroinflammatory diseases

Disruption of the blood-brain and blood-spinal cord barriers (BBB and BSCB, respectively) and immune cell infiltration are early pathophysiological hallmarks of multiple sclerosis (MS), its animal model experimental autoimmune encephalomyelitis (EAE), and neuromyelitis optica (NMO). However, their contribution to disease initiation and development remains unclear. In this study, we induced EAE in lys-eGFP-ki mice and performed single, nonterminal intravital imaging to investigate BSCB permeability simultaneously with the kinetics of GFP(+) myeloid cell infiltration. We observed a loss in BSCB integrity within a day of disease onset, which paralleled the infiltration of GFP(+) cells into the CNS and lasted for ∼4 d. Neutrophils accounted for a significant proportion of the circulating and CNS-infiltrating myeloid cells during the preclinical phase of EAE, and their depletion delayed the onset and reduced the severity of EAE while maintaining BSCB integrity. We also show that neutrophils collected from the blood or bone marrow of EAE mice transmigrate more efficiently than do neutrophils of naive animals in a BBB cell culture model. Moreover, using intravital videomicroscopy, we demonstrate that the IL-1R type 1 governs the firm adhesion of neutrophils to the inflamed spinal cord vasculature. Finally, immunostaining of postmortem CNS material obtained from an acutely ill multiple sclerosis patient and two neuromyelitis optica patients revealed instances of infiltrated neutrophils associated with regions of BBB or BSCB leakage. Taken together, our data provide evidence that neutrophils are involved in the initial events that take place during EAE and that they are intimately linked with the status of the BBB/BSCB.

A high-affinity natural autoantibody from human cord blood defines a physiologically relevant epitope on the FcepsilonRIalpha.

Natural Abs represent the indigenous immune repertoire and are thus present at birth and persist throughout life. Previously, human autoantibodies to the alpha domain of the high-affinity IgE receptor (FcepsilonRIalpha) have been isolated from Ab libraries derived from normal donors and patients with chronic urticaria. To investigate whether these anti-FcepsilonRIalpha Abs are present in the germline repertoire, we constructed a phage Fab display library from human cord blood, which represents the naive immune repertoire before exposure to exogenous Ags. All isolated clones specific to the FcepsilonRIalpha had the same sequence. This single IgM Ab, named CBMalpha8, was strictly in germline configuration and had high affinity and functional in vitro anaphylactogenic activity. Inhibition experiments indicated an overlapping epitope on the FcepsilonRIalpha recognized by both CBMalpha8 and the previously isolated anti-FcepsilonRIalpha Abs from autoimmune and healthy donors. This common epitope on FcepsilonRIalpha coincides with the binding site for IgE. Affinity measurements demonstrated the presence of Abs showing CBMalpha8-like specificity, but with a significantly lower affinity in i.v. Ig, a therapeutic multidonor IgG preparation. We propose a hypothesis of escape mutants, whereby the resulting lower affinity IgG anti-FcepsilonRIalpha Abs are rendered less likely to compete with IgE for binding to FcepsilonRIalpha.

Contemporary spinal cord protection during thoracic and thoracoabdominal aortic surgery and endovascular aortic repair: a position paper of the vascular domain of the European Association for Cardio-Thoracic Surgery†.

Ischaemic spinal cord injury (SCI) remains the Achilles heel of open and endovascular descending thoracic and thoracoabdominal repair. Neurological outcomes have improved coincidentially with the introduction of neuroprotective measures. However, SCI (paraplegia and paraparesis) remains the most devastating complication. The aim of this position paper is to provide physicians with broad information regarding spinal cord blood supply, to share strategies for shortening intraprocedural spinal cord ischaemia and to increase spinal cord tolerance to transitory ischaemia through detection of ischaemia and augmentation of spinal cord blood perfusion. This study is meant to support physicians caring for patients in need of any kind of thoracic or thoracoabdominal aortic repair in decision-making algorithms in order to understand, prevent or reverse ischaemic SCI. Information has been extracted from focused publications available in the PubMed database, which are cohort studies, experimental research reports, case reports, reviews, short series and meta-analyses. Individual chapters of this position paper were assigned and after delivery harmonized by Christian D. Etz, Ernst Weigang and Martin Czerny. Consequently, further writing assignments were distributed within the group and delivered in August 2014. The final version was submitted to the EJCTS for review in September 2014.

Longitudinal extension of myelomalacia by intramedullary and subdural hemorrhage in a canine model of spinal cord injury

BACKGROUND CONTEXT In canine intervertebral disc (IVD) extrusion, a spontaneous animal model of spinal cord injury, hemorrhage is a consistent finding. In rodent models, hemorrhage might be involved in secondary tissue destruction by biochemical mechanisms. PURPOSE This study aimed to investigate a causal association between the extents of intramedullary, subdural and epidural hemorrhage and the severity of spinal cord damage following IVD extrusion in dogs. STUDY DESIGN/SETTING A retrospective study using histologic spinal cord sections from 83 dogs euthanized following IVD extrusion was carried out. METHODS The degree of hemorrhage (intramedullary, subdural, epidural), the degree of spinal cord damage in the epicenter (white and gray matter), and the longitudinal extent of myelomalacia were graded. Associations between the extent of hemorrhage and the degree of spinal cord damage were evaluated statistically. RESULTS Intramedullary and subdural hemorrhages were significantly associated with the degree of white (p<.001/ p=.004) and gray (both p<.001) matter damage, and with the longitudinal extension of myelomalacia (p<.001/p=.005). Intriguingly, accumulation of hemorrhagic cord debris inside or dorsal to a distended and ruptured central canal in segments distant to the epicenter of the lesion was observed exhibiting a wave-like pattern on longitudinal assessment. The occurrence of this debris accumulation was associated with high degrees of tissue destruction (all p<.001). CONCLUSIONS Tissue liquefaction and increased intramedullary pressure associated with hemorrhage are involved in the progression of spinal cord destruction in a canine model of spinal cord injury and ascending or descending myelomalacia. Functional and dynamic studies are needed to investigate this concept further.

Long-bone fractures in persons with spinal cord injury

STUDY DESIGN Retrospective data analysis. OBJECTIVES To document fracture characteristics, management and related complications in individuals with traumatic spinal cord injury (SCI). SETTING Rehabilitation centre for SCI individuals. METHOD Patients' records were reviewed. Patients with traumatic SCI and extremity fractures that had occurred after SCI were included. Patient characteristics, fractured bone, fracture localisation, severity and management (operative/conservative), and fracture-related complications were extracted. RESULTS A total of 156 long-bone fractures in 107 SCI patients (34 women and 73 men) were identified. The majority of patients were paraplegics (77.6%) and classified as American Spinal Injury Association Impairment Scale A (86.0%). Only the lower extremities were affected, whereby the femur (60.9% of all fractures) was fractured more frequently than the lower leg (39.1%). A total of 70 patients (65.4%) had one fracture, whereas 37 patients (34.6%) had two or more fractures. Simple or extraarticular fractures were most common (75.0%). Overall, 130 (83.3%) fractures were managed operatively. Approximately half of the femur fractures (48.2%) were treated with locking compression plates. In the lower leg, fractures were mainly managed with external fixation (48.8%). Conservative fracture management was applied in 16.7% of the cases and consisted of braces or a well-padded soft cast. Fracture-associated complications were present in 13.5% of the cases but did not differ significantly between operative (13.1%) and conservative (15.4%) fracture management. CONCLUSION SCI was associated with simple or extraarticular fractures of the distal femur and the lower leg. Fractures were mainly managed operatively with a low complication rate.

Description and repeatability of a newly developed spinal cord injury scale for dogs.

The objectives of this study were to describe a new spinal cord injury scale for dogs, evaluate repeatability through determining inter-rater variability of scores, compare these scores to another established system (a modified Frankel scale), and determine if the modified Frankel scale and the newly developed scale were useful as prognostic indicators for return to ambulation. A group of client-owned dogs with spinal cord injury were examined by 2 independent observers who applied the new Texas Spinal Cord Injury Score (TSCIS) and a modified Frankel scale that has been used previously. The newly developed scale was designed to describe gait, postural reactions and nociception in each limb. Weighted kappa statistics were utilized to determine inter-rater variability for the modified Frankel scale and individual components of the TSCIS. Comparisons were made between raters for the overall TSCIS score and between scales using Spearman's rho. An additional group of dogs with surgically treated thoracolumbar disk herniation was enrolled to look at correlation of both scores with spinal cord signal characteristics on magnetic resonance imaging (MRI) and ambulatory outcome at discharge. The actual agreement between raters for the modified Frankel scale was 88%, with a weighted kappa value of 0.93. The TSCIS had weighted kappa scores for gait, proprioceptive positioning and nociception components that ranged from 0.72 to 0.94. Correlation between raters for the overall TSCIS score was Spearman's rho=0.99 (P<0.001). Comparison of the overall TSCIS score to the modified Frankel score resulted in a Spearman's rho value of 0.90 (P<0.001). The modified Frankel score was weakly correlated with the length of hyperintensity of the spinal cord: L2 vertebral body length ratio on mid-sagittal T2-weighted MRI (Spearman's rho=-0.45, P=0.042) as was the overall TSCIS score (Spearman's rho=-0.47, P=0.037). There was also a significant difference in admitting modified Frankel scores (P=0.029) and admitting overall TSCIS scores (P=0.02) between dogs that were ambulatory at discharge and those that were not. Results from this study suggest that the TSCIS is an easy to administer scale for evaluating canine spinal cord injury based on the standard neurological exam and correlates well with a previously described modified Frankel scale.