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.

Cervical spinal locking plate in combination with cortical ring allograft for a one level fusion in dogs with cervical spondylotic myelopathy.

OBJECTIVE To evaluate use of a surgical technique commonly used in humans for treatment of cervical spondylotic myelopathy (CSM) in dogs. DESIGN Prospective case series. ANIMALS Dogs with CSM (n=10). METHODS Dogs weighing >30 kg that had CSM at 1 vertebral articulation were eligible for inclusion. Dogs had vertebral column distraction/fusion performed using a cortical ring allograft, cancellous autograft, and a spinal locking plate. Dogs were evaluated temporally by repeat neurological examinations and by client perception of postsurgical outcome, determined by telephone interview. RESULTS Nine dogs survived the immediate postoperative period. Seven of 8 dogs had moderate to complete improvement without recurrence (mean follow-up, 2.48 years). The most common postsurgical complications were screw loosening (n=4) and plate shifting (2), neither of which required surgical revision. One dog had pseudoarthrosis that may have negatively impacted outcome. CONCLUSION Treatment of single level CSM in dogs with ring allograft and a spinal locking plate system may lead to successful outcomes. The major problems encountered with included cost of the implants and adjusting the system designed for humans to fit the vertebral column of a dog. CLINICAL RELEVANCE For dogs with CSM at a single level, the use of a spinal locking plate in combination with a cortical ring allograft can be an effective surgical treatment. Costs of the implants as well as anatomic differences in dogs make this type of surgery less appealing.

Evaluation of a questionnaire for obtaining owner-perceived, weighted quality-of-life assessments for dogs with spinal cord injuries.

OBJECTIVE To evaluate a questionnaire for obtaining owner-perceived, weighted quality-oflife assessments for dogs with spinal cord injuries. DESIGN Evaluation study. Animals-100 dogs with spinal cord injuries and 48 healthy control dogs. PROCEDURES The questionnaire was adapted from a questionnaire (the schedule for the evaluation of individual quality of life-direct weighting) used for human patients. Specifically, owners were asked to identify 5 areas or activities they believed had the most influence on their dogs' quality of life, assess their dogs' current status in each of those areas, and provide a weighting for the importance of each area. Results were used to construct a weighted quality-of-life score ranging from 0 to 100 for each dog. Owners were also asked to provide a quality-of-life score with a visual analog scale (VAS). RESULTS A good correlation was found between weighted and VAS quality-of-life scores. Dogs with spinal cord injuries had weighted quality-of-life scores that were significantly lower than scores for control dogs. Quality-of-life areas and activities provided by owners of dogs with spinal cord injuries were similar to areas and activities provided by owners of healthy control dogs and could mostly be encompassed by 5 broader domains: mobility, play or mental stimulation, health, companionship, and other. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that the questionnaire could be used to obtain owner-perceived, weighted quality-of-life assessments for dogs with spinal cord injuries. Obtaining owner-perceived quality-of-life assessments for individual dogs should allow veterinarians to better address quality-of-life concerns and expectations of owners.

Rapid assessment of internodal myelin integrity in central nervous system tissue

Monitoring pathology/regeneration in experimental models of de-/remyelination requires an accurate measure not only of functional changes but also of the amount of myelin. We tested whether X-ray diffraction (XRD), which measures periodicity in unfixed myelin, can assess the structural integrity of myelin in fixed tissue. From laboratories involved in spinal cord injury research and in studying the aging primate brain, we solicited "blind" samples and used an electronic detector to record rapidly the diffraction patterns (30 min each pattern) from them. We assessed myelin integrity by measuring its periodicity and relative amount. Fixation of tissue itself introduced +/-10% variation in periodicity and +/-40% variation in relative amount of myelin. For samples having the most native-like periods, the relative amounts of myelin detected allowed distinctions to be made between normal and demyelinating segments, between motor and sensory tracts within the spinal cord, and between aged and young primate CNS. Different periodicities also allowed distinctions to be made between samples from spinal cord and nerve roots and between well-fixed and poorly fixed samples. Our findings suggest that, in addition to evaluating the effectiveness of different fixatives, XRD could also be used as a robust and rapid technique for quantitating the relative amount of myelin among spinal cords and other CNS tissue samples from experimental models of de- and remyelination.

The ocular motor features of adult-onset alexander disease: a case and review of the literature

A 51-year-old Chinese man presented with gaze-evoked nystagmus, impaired smooth pursuit and vestibular ocular reflex cancellation, and saccadic dysmetria, along with a family history suggestive of late-onset autosomal dominant parkinsonism. MRI revealed abnormalities of the medulla and cervical spinal cord typical of adult-onset Alexander disease, and genetic testing showed homozygosity for the p.D295N polymorphic allele in the gene encoding the glial fibrillary acidic protein. A review of the literature shows that ocular signs are frequent in adult-onset Alexander disease, most commonly gaze-evoked nystagmus, pendular nystagmus, and/or oculopalatal myoclonus, and less commonly ptosis, miosis, and saccadic dysmetria. These signs are consistent with the propensity of adult-onset Alexander disease to cause medullary abnormalities on neuroimaging.

Neurological outcome, working capacity and prognostic factors of patients with SCIWORA

STUDY DESIGN: Retrospective case review. OBJECTIVES: In the present study, the neurological outcome, retirement and prognostic factors of patients with spinal cord injury without radiographic abnormality (SCIWORA) were evaluated. SETTING: Swiss national work accident insurance database. METHODS: The medical histories of 32 patients who were insured by the Swiss Accident Insurance Fund (SUVA) and had SCIWORA between 1995 and 2004 were evaluated thoroughly. Moreover, all available magnetic resonance imaging (MRI) scans were evaluated. RESULTS: At the last follow-up, none of the patients had complete spinal cord injury, only 4 patients had severe deficits and 12 patients had normal motor and sensory function in the neurological examination. However, only 7 out of 32 patients had returned to full-time work and 10 out of 32 patients were fully retired. Both the presence of spinal cord change (ρ=0.51) and higher maximum spinal cord compression (ρ=0.57) in MRI scan correlated with the likelihood for retirement; older age (ρ=0.38) and physical load of work (ρ=0.4) correlated with retirement to a lesser extent. CONCLUSION: Although the neurological outcome of SCIWORA is mostly good, the retirement rate is high. Presence of spinal cord change and severity of cord compression are the best predictors for the degree of retirement.

Isolated vertebral fractures give elevated serum protein S-100B levels

ABSTRACT: BACKGROUND: Serum protein S-100B determinations have been widely proposed in the past as markers of traumatic brain injury and used as a predictor of injury severity and outcome. The purpose of this prospective observational case series was therefore to determine S-100B serum levels in patients with isolated injuries to the back. METHODS: Between 1 February and 1 May 2008, serum samples for S-100B analysis were obtained within 1 hour of injury from 285 trauma patients. All patients with a head injury, polytrauma, and intoxicated patients were excluded to select isolated injuries to the spine. 19 patients with isolated injury of the back were included. Serum samples for S-100B analysis and CT spine were obtained within 1 hours of injury. RESULTS: CT scans showed vertebral fractures in 12 of the 19 patients (63%). All patients with fractures had elevated S-100B levels. Amongst the remaining 7 patients without a fracture, only one patient with a severe spinal contusion had an S-100B concentration above the reference limit. The mean S-100B value of the group with fractures was more than 4 times higher than in the group without fractures (0.385 vs 0.087 mug/L, p = 0.0097). CONCLUSION: Our data, although limited due to a very small sample size, suggest that S-100B serum levels might be useful for the diagnosis of acute vertebral body and spinal cord injury with a high negative predictive power. According to the literature, the highest levels of serum S-100B are found when large bones are fractured. If a large prospective study confirms our findings, determining the S-100B level may contribute to more selective use of CT and MRI in spinal trauma.

Association between various physical factors and acute thoracolumbar intervertebral disk extrusion or protrusion in Dachshunds.

OBJECTIVE To determine whether body weight, body condition score, or various body dimensions were associated with acute thoracolumbar intervertebral disk extrusion or protrusion and whether any of these factors were associated with severity of clinical signs in Dachshunds. DESIGN Cross-sectional clinical study. ANIMALS 75 Dachshunds with (n = 39) or without (36) acute thoracolumbar intervertebral disk extrusion or protrusion. PROCEDURES Signalment, various body measurements, body weight, body condition score, and spinal cord injury grade were recorded at the time of initial examination. RESULTS Mean T1-S1 distance and median tuber calcaneus-to-patellar tendon (TC-PT) distance were significantly shorter in affected than in unaffected dogs. A 1-cm decrease in T1-S1 distance was associated with a 2.1-times greater odds of being affected, and a 1-cm decrease in TC-PT distance was associated with an 11.1-times greater odds of being affected. Results of multivariable logistic regression also indicated that affected dogs were taller at the withers and had a larger pelvic circumference than unaffected dogs, after adjusting for other body measurements. Results of ordinal logistic regression indicated that longer T1-S1 distance, taller height at the withers, and smaller pelvic circumference were associated with more severe spinal cord injury. CONCLUSIONS AND CLINICAL RELEVANCE Results suggest that certain body dimensions may be associated with acute thoracolumbar intervertebral disk extrusion or protrusion in Dachshunds and, in affected dogs, with severity of neurologic dysfunction.

Unique paleopathology in a pre-Columbian mummy remnant from Southern Peru--severe cervical rotation trauma with subluxation of the axis as cause of death

We describe the multidisciplinary findings in a pre-Columbian mummy head from Southern Peru (Cahuachi, Nazca civilisation, radiocarbon dating between 120 and 750 AD) of a mature male individual (40-60 years) with the first two vertebrae attached in pathological position. Accordingly, the atlanto-axial transition (C1/C2) was significantly rotated and dislocated at 38° angle associated with a bulging brownish mass that considerably reduced the spinal canal by circa 60%. Using surface microscopy, endoscopy, high-resolution multi-slice computer tomography, paleohistology and immunohistochemistry, we identified an extensive epidural hematoma of the upper cervical spinal canal-extending into the skull cavity-obviously due to a rupture of the left vertebral artery at its transition between atlas and skull base. There were no signs of fractures of the skull or vertebrae. Histological and immunohistochemical examinations clearly identified dura, brain residues and densely packed corpuscular elements that proved to represent fresh epidural hematoma. Subsequent biochemical analysis provided no evidence for pre-mortal cocaine consumption. Stable isotope analysis, however, revealed significant and repeated changes in the nutrition during his last 9 months, suggesting high mobility. Finally, the significant narrowing of the rotational atlanto-axial dislocation and the epidural hematoma probably caused compression of the spinal cord and the medulla oblongata with subsequent respiratory arrest. In conclusion, we suggest that the man died within a short period of time (probably few minutes) in an upright position with the head rotated rapidly to the right side. In paleopathologic literature, trauma to the upper cervical spine has as yet only very rarely been described, and dislocation of the vertebral bodies has not been presented.

The changing epidemiology of spinal trauma: a 13-year review from a Level I trauma centre

Spinal injuries secondary to trauma are a major cause of patient morbidity and a source of significant health care expenditure. Increases in traffic safety standards and improved health care resources may have changed the characteristics and incidence of spinal injury. The purpose of this study was to review a single metropolitan Level I trauma centre's experience to assess the changing characteristics and incidence of traumatic spinal injuries and spinal cord injuries (SCI) over a 13-year period.

Spinal MRI supporting myelopathic origin of early symptoms in unsuspected cobalamin deficiency

We report two patients with subjectively progressive sensory symptoms and gait disturbance due to cobalamin deficiency, but only slight or absent abnormalities on neurological examination. In both patients, spinal MRI provided evidence for a myelopathic origin of the symptoms, disclosing characteristic T(2) hyperintense signal alterations confined to the posterior columns of the cervical and thoracic spinal cord. The patients illustrate the early clinical presentation of subacute combined degeneration (SCD) with a sensory neuropathy starting with acroparesthesia and Lhermitte's sign. Furthermore, the diagnostic value of spinal MRI for early diagnosis of SCD with characteristic findings is highlighted.

Congenital cervical kyphosis in two young sighthounds

Introduction: Cervical vertebral (C) malformation is rarely reported in large breed dogs. Congenital cervical kyphosis (CCK) may result from defects of vertebral segmentation, failure of formation or both. This report describes two cases of C3-C4 CCK in young sighthounds, treated surgically. Case description: An 18-month-old female Deerhound and a six-week-old female Borzoi dog were presented because of the complaints of reluctance to exercise and signs of of neck pain. Both dogs were neurologically normal. Diagnostic imaging revealed C3-C4 deformity, moderate kyphosis, and spinal canal stenosis associated with chronic spinal cord pressure atrophy. Both dogs underwent surgical treatment. Results: A staged two-step surgery starting with dorsal decompression was elected in the Deerhound. After the first surgical procedure, the dog developed focal myelomalacia and phrenic nerve paralysis and was euthanatized. A ventral distraction-fusion technique with two locking plates was performed in the Borzoi. This patient recovered uneventfully and long-term follow-up computed tomography revealed complete spondylodesis. Clinical significance: Until now, CCK has only been described in sighthounds. Congenital cervical kyphosis might be considered a differential diagnosis in these breeds that are presented with signs of cervical pain. Ventral realignment-fusion and bone grafting may be considered for surgical treatment, although the earliest age at which this procedure can and should be performed remains unclear.