Nomograms Predict Survival Outcome of Primary Intramedullary Spinal Cord Lymphoma Patients.

BACKGROUND Primary intramedullary spinal cord lymphoma (PISCL) is a rare cause of myelopathies. Considering its poor prognosis, it is essential to determine the appropriate treatment strategies and to develop nomograms to predict survival outcome for PISCL patients. MATERIAL AND METHODS Data were collected from the Surveillance, Epidemiology and End Results (SEER) database. We used 364 patients to investigate overall survival (OS) and 289 patients for cancer-specific survival (CSS). Kaplan-Meier method was to evaluate correlations of survival with different treatment strategies and clinicopathologic factors. Univariate and multivariable analyses were conducted to assess OS and CSS based on different variables. Risk factors were integrated to build nomograms. RESULTS Most of the 414 PISCL patients diagnosed with positive histology had diffuse B cell lymphoma, were under 60 years old, were male, were of white race, had 1 primary tumor, were married, were low stage, and had previously undergone chemotherapy. We found that radiation therapy had no effect on patient OS and CSS, and patients receiving chemotherapy alone tended to have better OS and CSS in comparison with other groups. In addition, we showed that clinicopathologic factors, including histologic type, age, stage, and marital status, could serve as independent prognostic factors for PISCL patient OS and CSS. These factors were utilized to construct nomograms. The calibration curves demonstrated good agreement. The concordance indexes for OS and CSS were 0.672 (P=0.024) and 0.683 (P=0.029), respectively. CONCLUSIONS Practical nomograms were established for patients' OS and CSS. Besides, this study can guild clinician to make the right decision for appropriate treatment of PISCL patients.

Clinical Characteristics of Dogs with Progressive Myelomalacia Following Acute Intervertebral Disc Extrusion.

BACKGROUND: Progressive myelomalacia (PMM) is a catastrophic disease associated with acute intervertebral disc extrusion (IVDE). Published data on the clinical characteristics of this disease are limited. OBJECTIVE: To describe the onset and progression of clinical signs of PMM in a large case cohort. ANIMALS: Fifty-one dogs, 18 with histopathologically confirmed PMM, 33 presumptively diagnosed based on clinical signs and diagnostic imaging. METHODS: Retrospective study. Dogs with confirmed IVDE and either a histopathologic diagnosis of PMM or a high clinical suspicion were identified by medical record search. Data on nature and progression of signs were extracted. RESULTS: Twenty-four of 51 dogs were Dachshunds. T12-T13 was the most common site of disc extrusion (12 of 56), and 18 of 55 of mid-to-caudal lumbar discs (between L3 and L6) were affected. Onset of PMM signs ranged from present at first evaluation (17/51) to 5 days after presentation, with 25 of 51 cases developing signs within 48 hours. Progression of signs from onset of PMM to euthanasia or death, excluding 7 cases euthanized at presentation, ranged from 1 to 13 days with 23 being euthanized within 3 days. Nonspecific systemic signs were documented in 30 of 51 dogs. CONCLUSION AND CLINICAL IMPORTANCE: The majority of dogs developed PMM within 2 days of presentation and was euthanized within another 3 days. However, onset can be delayed up to 5 days after presentation with progression to euthanasia taking as long as 2 weeks. Mid-to-caudal lumbar discs might be associated with an increased risk of PMM.

A New Classification for Pathologies of Spinal Meninges-Part 2: Primary and Secondary Intradural Arachnoid Cysts.

BACKGROUND: Spinal intradural arachnoid cysts are rare causes of radiculopathy or myelopathy. Treatment options include resection, fenestration, or cyst drainage. OBJECTIVE: To classify intradural spinal arachnoid cysts and present results of their treatment. METHODS: Among 1519 patients with spinal space occupying lesions, 130 patients demonstrated intradural arachnoid cysts. Neuroradiological and surgical features were reviewed and clinical data analyzed. RESULTS: Twenty-one patients presented arachnoid cysts as a result of an inflammatory leptomeningeal reaction related to meningitis, subarachnoid hemorrhage, intrathecal injections, intradural surgery, or trauma, ie, secondary cysts. For the remaining 109 patients, no such history could be elucidated, ie, primary cysts. Forty-six percent of primary and 86% of secondary cysts were associated with syringomyelia. Patients presented after an average history of 53 ± 88 months. There were 122 thoracic and 7 lumbar cysts plus 1 cervical cyst. Fifty-nine patients with primary and 15 patients with secondary cysts underwent laminotomies with complete or partial cyst resection and duraplasty. Mean follow-up was 57 ± 52 months. In the first postoperative year, profound improvements for primary cysts were noted, in contrast to marginal changes for secondary cysts. Progression-free survival for 10 years following surgery was determined as 83% for primary compared to 15% for secondary cysts. Despite differences in clinical presentation, progression-free survival was almost identical for patients with or without syringomyelia. CONCLUSIONS: Complete or partial resection leads to favorable short- and long-term results for primary arachnoid cysts. For secondary cysts, surgery can only provide clinical stabilization for a limited time due to the often extensive arachnoiditis.

Management Strategy of Osteoblastomas Localized in the Occipitocervical Junction.

OBJECTIVE: The aim of this article was to analyze extracted patient data from the literature and highlight the best treatment options and survival outcomes for osteoblastomas in the occipitocervical region. METHODS: A systematic literature search method was used to select articles containing information about the demographic features, tumor location, treatment characteristics, adjuvant therapies, and follow-up time. RESULTS: From 25 articles, 31 cases of osteoblastoma in the occipitocervical junction were selected for analysis. Average patient age was 17 years (range, 5-57 years); there were 21 male (67%) and 10 female (33%) patients. All patients had cervical pain as the presenting symptom. Other symptoms included torticollis (0.13%) and sensory or motor neurologic deficits (0.16%). The average follow-up time was 41 months, and the local recurrence rate was 0.125%. Recommendations of each article are categorized and discussed in detail. CONCLUSIONS: Osteoblastoma is a rare entity in the occipitocervical region, so treatment experiences are limited and mostly based on case reports. To determine the best treatment for these lesions, osteoblastomas should be staged using the Enneking staging system; different methods may be recommended for different stages, and the feasibility of fusion depends on the remaining amount of bony structures and joints. Additional adjuvant therapies may be recommended only in special cases.

Life Expectancy After Cervical En Bloc Laminoplasty: Analysis of Data Following More Than 20 Years.

STUDY DESIGN: Case series. OBJECTIVE: To clarify the following questions How long after cervical laminoplasty did the patients die? What were the causes of the death? Was the severity of the neurological dysfunction related to early death? SUMMARY OF BACKGROUND DATA: Life expectancy in patients with cervical myelopathy is unclear. Cervical laminoplasty was performed in 216 patients between 1981 and 1994. It was possible to follow 148 patients for more than 20 years. We used the data of the 68 survivors and the 80 patients had already died. METHODS: As for the patients who died by the final follow-up, the survival rate was analyzed by a Kaplan-Meier plot; the results were compared between the patients with cervical spondylosis (CS) and the patients with ossification of the posterior longitudinal ligament (OPLL). The causes of the death were assessed. The neurological evaluation was graded using the score devised by the Japanese Orthopaedic Association (JOA). The pre- and postoperative scores were compared between the patients in the died group (D group) and the surviving patients group (S group). RESULTS: The mean period from surgery to death was 13.4 ±â€Š7.4 years. There was no difference in the survival rate between patients with CS and patients with OPLL. The most frequent cause of death was malignant tumor followed by ischemic heart disease. Preoperative JOA score in the D group was lower than that in the S group. There was no statistical difference in postoperative JOA score between the two groups. CONCLUSION: The patients who underwent cervical laminoplasty caused by compression myelopathy due to CS and OPLL had a long life expectancy, averaging more than 13 years. Life expectancy did not differ between patients with CS and patients with OPLL. Neurological deficit did not directly affect the life expectancy. LEVEL OF EVIDENCE: 4.

Prolonged length of stay after posterior surgery for cervical spondylotic myelopathy in patients over 65years of age.

Prolonged length of stay (PLOS) has been associated with increased hospital resource utilization and worsened patient outcomes in multiple studies. In this study, we defined and identified factors associated with PLOS after posterior surgery for cervical spondylotic myelopathy in patients over the age of 65. PLOS was defined as length of stay beyond the "prolongation point" (that is, the day after which discharge rates begin to decline). Using the United States Nationwide Inpatient Sample database, 2742 patients met inclusion criteria, out of whom 16.5% experienced PLOS (stay beyond 6days). After multivariate analysis, increasing age was independently associated with PLOS (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.02-1.06). Multiple comorbid conditions were associated with PLOS, including alcohol abuse (OR 3.85, 95% CI 1.87-7.94), congestive heart failure (OR 1.72, 95% CI 1.11-2.64), obesity (OR 1.70, 95% CI 1.14-2.55), and deficiency anemia (OR 1.44, 95% CI 1.01-2.05); the strongest associated operative parameter was blood transfusion (OR 2.39, 95% CI 1.75-3.28). Major complications independently associated with PLOS were deep vein thrombosis (OR 18.32, 95% CI 6.50-51.61), myocardial infarction (OR 8.98, 95% CI 2.92-27.56), pneumonia (OR 6.67, 95% CI 3.17-14.05), acute respiratory failure (OR 6.27, 95% CI 3.43-11.45), hemorrhage/hematoma (OR 5.04, 95% CI 2.69-9.44), and implant-related complications (OR 2.49, 95% CI 1.24-4.98). Average total hospital charges for patients who experienced PLOS were $122,965 US dollars, compared to $76,870 for the control group (p<0.001). Mortality for patients who experienced PLOS was 2.7% versus 0.5% for patients who did not epxerience PLOS (p<0.001). In conclusion, patients over the age of 65 who underwent posterior surgery for cervical myelopathy and stayed over 6days in hospital were defined as having PLOS. Hospital charges and mortality rates were significantly higher for patients who experienced PLOS. Potentially modifiable and/or preventable risk factors were also identified.

The Impact of Advanced Age on Peri-Operative Outcomes in the Surgical Treatment of Cervical Spondylotic Myelopathy: A Nationwide Study Between 2001 and 2010.

STUDY DESIGN: Retrospective multicenter database review. OBJECTIVE: The aim of this study was to evaluate national postoperative outcomes and hospital characteristics trends from 2001 to 2010 for advanced age CSM patients. SUMMARY OF BACKGROUND DATA: Recent studies show increases in US cervical spine surgeries and CSM diagnoses. However, few have compared national outcomes for elderly and younger CSM patients. METHODS: A Nationwide Inpatient Sample (NIS) analysis from 2001 to 2010, including CSM patients 25+ who underwent anterior and/or posterior cervical fusion or laminoplasty. Fractures, 9+ levels fused, or any cancers were excluded. Measures included demographics, outcomes, and hospital-related data for 25 to 64 versus 65+ and 65 to 75 versus 76+ age groups. Univariate and logistic regression modeling evaluated procedure-related complications risk in 65+ and 76+ age groups (OR[95% CI]). RESULTS: Discharges for 35,319 patients in the age range of 25 to 64 years and 19,097 at the age 65+ years were identified. Average comorbidity indices for patients at 65+ years were higher compared to the 25 to 64 years age group (0.79 vs. 0.0.44, P < 0.0001), as was the total complications rate (11.39% vs. 5.93%, P < 0.0001) and charges ($57,449.94 vs. $49,951.11, P < 0.0001). Hospital course for aged 65+ patients was longer (4.76 vs. 3.26 days, P < 0.0001). Mortality risk was higher in the 65+ cohort (3.38[2.93-3.91]), adjusted for covariates. 65+ patients had increased risk of all complications except device-related, for which they had decreased risk (0.61[0.56-0.67]). Patients 76+ years displayed increased hospital charges ($59,197.60 vs. $56,601.44, P < 0.001) and courses (5.77 vs. 4.28 days, P < 0.001) compared to those in the age group 65 to 75 years. These same patients presented with increased Deyo scores (0.83 vs. 0.77, P < 0.001), had increased total complications rate (13.87% vs. 10.20%, P < 0.001), and displayed increased risk for postoperative shock (6.34 [11.16-3.60], P < 0.001), digestive system (1.92 [2.40-1.54], P < 0.001), and wound dehiscence (1.71 [2.56-1.15], P < 0.001). CONCLUSION: Patients aged 65+ years undergoing CSM surgical management have a higher mortality risk, more procedure-related complications, higher comorbidity burden, longer hospital course, and higher charges. This study provides clinically useful data for surgeons to educate patients and to improve outcomes.

Neural stem/progenitor cell-laden microfibers promote transplant survival in a mouse transected spinal cord injury model.

Previous studies have demonstrated that transplantation of neural stem/progenitor cells (NS/PCs) into the lesioned spinal cord can promote functional recovery following incomplete spinal cord injury (SCI) in animal models. However, this strategy is insufficient following complete SCI because of the gap at the lesion epicenter. To obtain functional recovery in a mouse model of complete SCI, this study uses a novel collagen-based microfiber as a scaffold for engrafted NS/PCs. We hypothesized that the NS/PC-microfiber combination would facilitate lesion closure as well as transplant survival in the transected spinal cord. NS/PCs were seeded inside the novel microfibers, where they maintained their capacity to differentiate and proliferate. After transplantation, the stumps of the transected spinal cord were successfully bridged by the NS/PC-laden microfibers. Moreover, the transplanted cells migrated into the host spinal cord and differentiated into three neural lineages (astrocytes, neurons, and oligodendrocytes). However, the NS/PC-laden scaffold could not achieve a neural connection between the rostral end of the injury and the intact caudal area of the spinal cord, nor could it achieve recovery of motor function. To obtain optimal functional recovery, a microfiber design with a modified composition may be useful. Furthermore, combinatorial therapy with rehabilitation and/or medications should also be considered for practical success of biomaterial/cell transplantation-based approaches to regenerative medicine.

Predictors of morbidity and mortality among patients with cervical spondylotic myelopathy treated surgically.

PURPOSE: The aim of this study is to report and quantify the associated factors for morbidity and mortality following surgical management of cervical spondylotic myelopathy (CSM). METHODS: The Nationwide Inpatient Sample (NIS) database was use to retrospectively review all patients over 25 years of age with a diagnosis of CSM who underwent anterior and/or posterior cervical fusion or laminoplasty between 2001 and 2010. The main outcome measures were total procedure-related complications and mortality. Multivariate regression analysis was used to identify demographic, comorbidity, and surgical parameters associated with increased morbidity and mortality risk [reported as: OR (95% CI)]. RESULTS: A total of 54,348 patients underwent surgical intervention for CSM with an overall morbidity rate of 9.83% and mortality rate of 0.43%. Comorbidities found to be associated with an increased complication rate included: pulmonary circulation disorders [6.92 (5.91-8.12)], pathologic weight loss [3.42 (3.00-3.90)], and electrolyte imbalance [2.82 (2.65-3.01)]. Comorbidities found to be associated with an increased mortality rate included: congestive heart failure [4.59 (3.62-5.82)], pulmonary circulation disorders [11.29 (8.24-15.47)], and pathologic weight loss [5.43 (4.07-7.26)]. Alternatively, hypertension [0.56 (0.46-0.67)] and obesity [0.36 (0.22-0.61)] were found to confer a decreased risk of mortality. Increased morbidity and mortality rates were also identified for fusions of 4-8 levels [morbidity: 1.55 (1.48-1.62), mortality: 1.80 (1.48-2.18)] and for age >65 years [morbidity: 1.65 (1.57-1.72), mortality: 2.74 (2.25-3.34)]. An increased morbidity rate was found for posterior-only [1.55 (1.47-1.63)] and combined anterior and posterior fusions [3.20 (2.98-3.43)], and an increased mortality rate was identified for posterior-only fusions [1.87 (1.40-2.49)]. Although revision fusions were associated with an increased morbidity rate [1.81 (1.64-2.00)], they were associated with a decreased rate of mortality [0.24 (0.10-0.59)]. CONCLUSION: The NIS database was used to provide national estimates of morbidity and mortality following surgical management of CSM in the United States. Several comorbidities, as well as demographic and surgical parameters, were identified as associated factors.

Myelopathy is associated with increased all-cause morbidity and mortality following anterior cervical discectomy and fusion: a study of 5256 patients in American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP).

STUDY DESIGN: Retrospective cohort. OBJECTIVE: To evaluate whether myelopathy is associated with increased morbidity and mortality after anterior cervical discectomy and fusion (ACDF) compared with other indications for this procedure. SUMMARY OF BACKGROUND DATA: ACDF is the most common surgical procedure for the management of a spectrum of cervical spine pathologies. As a more advanced condition, myelopathy is generally thought to be associated with higher morbidity and mortality after this procedure, but there is limited evidence to support this supposition. The current study compares outcomes of ACDF procedures performed for myelopathy with those performed for other indications, controlling for other patient factors. METHODS: Patients who underwent ACDF between 2010 and 2012 were identified in the American College of Surgeons National Surgical Quality Improvement Program database. Patients with myelopathy were identified by diagnosis codes for cervical myelopathy. Bivariate and multivariate logistic regressions were performed to compare 30-day adverse events and readmission between groups. Multivariate analyses controlled for patient and surgical characteristics. RESULTS: A total of 5256 ACDF procedures met inclusion criteria, of which 1425 (27.3%) were performed for cervical myelopathy. Patients with myelopathy were older and were less healthy than patients without myelopathy. Multivariate analysis controlling for baseline patient characteristics found that patients with myelopathy were at significantly increased risk of any adverse event (odds ratio = 1.5), any severe adverse event (odds ratio = 1.8), and death (odds ratio = 8.9) compared with patients without myelopathy. CONCLUSION: After adjusting for baseline patient characteristics, not only were any adverse events and serious adverse events more common after ACDF for patients with myelopathy than for patients without myelopathy, but mortality was approximately 9 times more likely. It is important for surgical planning and patient counseling to keep this significant difference in mind for this common procedure that has different morbidities based on the pathology for which it is performed. LEVEL OF EVIDENCE: 3.

Diffusion tensor MRI of spinal decompression sickness.

In order to develop more sensitive imaging tools for clinical use and basic research of spinal decompression sickness (DCS), we used diffusion tensor MRI (DTI) validated by histology to assess DCS-related tissue injury in sheep spinal cords. DTI is based on the measurement of water diffusion indices, including fractional anisotropy (FA) and mean diffusion (MD) to detect tissue microstructural abnormalities. In this study, we measured FA and MD in white and gray matter spinal cord regions in samples taken from sheep following hyperbaric exposure to 60-132 fsw and 0-180 minutes of oxygen pre-breathing treatment before rapid decompression. The main finding of the study was that decompression from >60 fsw resulted in reduced FA that was associated with cell death and disrupted tissue microstructure in spinal cord white matter tracts. Additionally, animals exposed to prolonged oxygen pre-breathing prior to decompression demonstrated reduced MD in spinal cord gray matter regions regardless of dive depth. To our knowledge, this is the first study to demonstrate the utility of DTI for the investigation of DCS-related injury and to define DTI biomarkers of spinal DCS.

Lateral extracavitary, costotransversectomy, and transthoracic thoracotomy approaches to the thoracic spine: review of techniques and complications.

STUDY DESIGN: Systematic review. OBJECTIVE: The authors review complications, as reported in the literature, associated with ventral and posterolateral approaches to the thoracic spine. SUMMARY OF BACKGROUND: The lateral extracavitary, costotransversectomy, and transthoracic thoracotomy techniques allow surgeons to access the ventral thoracic spine for a wide range of spinal disorders including tumor, degeneration, trauma, and infection. Although the transthoracic thoracotomy has been used traditionally to reach the ventral thoracic spine when access to the vertebral body is required, modifications to the various dorsal approaches have enabled surgeons to achieve goals of decompression, reconstruction, and stabilization through a single approach. METHODS: A systematic Medline search from 1991 to 2011 was performed to identify series reporting clinical data related to these surgical approaches. The morbidity associated with each approach is reviewed and strategies for complications avoidance are discussed. RESULTS: Four thousand six hundred seventy-seven articles that assessed outcomes of the approaches to the thoracic spine were identified; of these 31 studies that consisted of 774 patients were selected for inclusion. A mean complication rate of 39%, 17%, and 15% for thoracotomy, lateral extracavitary, and costotransversectomy, respectively, was determined. The thoracotomy approach had the highest reoperation (3.5%) and mortality rates (1.5%). The specific complications and neurological outcomes were categorized. CONCLUSIONS: Outcomes of the surgical approaches to the thoracic spine have been reported with great detail in the literature. There are limited studies comparing the respective advantages and disadvantages and the differences in technique and outcome between these approaches. The present review suggests that in contrast to the historical experience of the laminectomy for thoracic spine disorders, these alternative approaches are safe and rarely associated with neurological deterioration. The differences between these approaches are based on their complication profiles. A thorough understanding of the regional anatomy will help avoid approach-related complications.

PNET spine: morbid and mortal, but ignored till late.

Spinal primitive neuroectodermal tumor (PNET) is rare. We present clinical, radiologic profile and treatment outcome of 15 spinal PNET patients from June 2003 to March 2010 treated with chemoradiotherapy. Median duration of backache was 6.5 months; all had features of myelopathy and/or radiculopathy; 5/15 (33.3%) patients were diagnosed initially as spinal tuberculosis. The event-free survival (EFS) was 24.73% at a median follow-up of 22 months. Complete functional recovery to treatment significantly predicted better EFS; 4 patients discontinued treatment because of poor functional recovery. It is important to recognize spinal PNET early to prevent permanent neurological damage, which in turn would improve compliance, quality of life, and perhaps EFS.

Lhermitte sign and myelopathy after irradiation of the cervical spinal cord in radiotherapy treatment of head and neck cancer.

BACKGROUND AND PURPOSE: The goal of this work was to examine toxicity and risk factors after irradiation of the cervical spinal cord. PATIENTS AND METHODS: A total of 437 patients irradiated for a laryngeal and oropharyngeal carcinoma were eligible (median follow-up 27 months). Spinal cord contouring was defined differently over time as anatomically defined spinal cord area (SCA) and the spinal cord on CT (SC) with a margin of 3 or 5 mm (SCP3/SCP5). RESULTS: None developed chronic progressive radiation myelopathy (CPRM) (maximum spinal dose 21.8-69 Gy); 3.9% (17/437) developed a Lhermitte sign (LS) with a median duration of 6 months (range 1-30 months) and was reversible in all patients. Risk factors for developing LS were younger age (52 vs. 61 years, p < 0.001), accelerated RT (12/17 patients, p < 0.005), and dose-volume relationships for SCA with ≥ 45 Gy of 14.15 cm(3) and 7.9 cm(3) for patients with and without LS, respectively. CONCLUSION: LS is more frequently observed in younger patients and in patients treated with accelerated radiotherapy. A dose-volume relationship was seen for V45 in the case of SCA. For higher doses, no clear dose-volume relationships were observed.

Post-anaesthetic myelopathy in a 3-year-old Friesian gelding.

A 3-year-old Friesian stallion was referred to the Department of Equine Sciences at Utrecht University with signs of colic. Laparotomy was performed and the stallion was castrated bilaterally because of an incarcerated inguinal hernia. Intestinal resection was not performed. Eight days postoperatively, the horse showed signs of severe colic and was admitted for re-laparotomy. After resection of 1.5 m of strangulated jejunum and severe intraoperative hypotension, bradycardia, and electrolyte disorders, the horse showed problems during recovery with signs of hindquarter paralysis. There was no pain perception in the hind limbs and there were no patellar or anal reflexes. The muscles of the hindquarters and the long extensor muscles of the back were soft and not painful on palpation. No improvement was seen 60 minutes after intravenous injection of corticosteroids. Because of the tentative diagnosis of post-anaesthetic myelopathy and its poor prognosis, and the fact that the horse was restless and did not accept being lifted with a sling system, the horse was euthanized with the owner's consent. Post-anaesthetic myelopathy is a rare neuropathological condition in the horse. Because of its low incidence, knowledge about its aetiology and contributing factors is rather limited. This case report presents the clinical observations and the anaesthetic protocol and compares this case with previously reported cases in the literature.

Modeling spinal cord contusion, dislocation, and distraction: characterization of vertebral clamps, injury severities, and node of Ranvier deformations.

Spinal cord contusion and transection models are widely used for studying spinal cord injury (SCI). Clinically, however, other biomechanical injury mechanisms such as vertebral dislocation and distraction frequently occur, but these injuries are difficult to produce in animals. We mechanically characterize a vertebral clamping strategy that enables the modeling of vertebral dislocation and distraction injuries--in addition to the standard contusion paradigm--in the rat cervical spine. These vertebral clamps have a stiffness of 83.6+/-18.9 N/mm and clamping strength 64.7+/-10.2N which allows injuries to be modeled at high-speed (approximately 100 cm/s). Logistic regression indicated that a moderate-to-severe injury, with an acute mortality rate of 10%, occurs at 2.6 mm of C4/5 dorso-ventral dislocation and 4.1 mm of rostro-caudal distraction between C4 and C5. Injuries produced by dislocation and distraction exhibited features of axonal damage that were absent in contusion injuries. We conducted morphometric analysis at the nodes of Ranvier using immunohistochemistry for potassium channels (Kv1.2) in the juxtaparanodal region. Following distraction injuries, elongated nodes of Ranvier were observed up to 4mm rostral to the lesion. In contrast, contusion injuries produced distortions in nodal geometry which were restricted to the vicinity of the lesion. The greatest deformations in node of Ranvier geometry occurred at the dislocation epicenter. Given the importance of white matter damage in SCI pathology, the distinctiveness of these injury patterns demonstrate that the dislocation and distraction injury models complement existing contusion models. Together, these three animal models span a broader clinical spectrum for more reliably gauging the potential human efficacy of therapeutic strategies.

Target-dependent B7-H1 regulation contributes to clearance of central nervous system infection and dampens morbidity.

The neurotropic coronavirus JHM strain of mouse hepatitis virus persists in oligodendroglia despite the presence of virus-specific CD8 T cells. Expression of programmed death 1 (PD-1) and B7-H1 were studied during acute and persistent infection to examine whether this negative regulatory mechanism contributes to CNS viral persistence. The majority of CNS-infiltrating CD8 T cells expressed PD-1, with the highest levels on virus-specific CD8 T cells. Moreover, despite control of infectious virus, CD8 T cells within the CNS of persistently infected mice maintained high PD-1 expression. Analysis of virus-susceptible target cells in vivo revealed that B7-H1 expression was regulated in a cell type-dependent manner. Oligodendroglia and microglia up-regulated B7-H1 following infection; however, although B7-H1 expression on oligodendroglia was prominent and sustained, it was significantly reduced and transient on microglia. Infection of mice deficient in the IFN-gamma or IFN-alpha/beta receptor demonstrated that B7-H1 expression on oligodendroglia is predominantly regulated by IFN-gamma. Ab blockade of B7-H1 on oligodendroglia in vitro enhanced IFN-gamma secretion by virus-specific CD8 T cells. More efficient virus control within the CNS of B7-H1-deficient mice confirmed inhibition of CD8 T cell function in vivo. Nevertheless, the absence of B7-H1 significantly increased morbidity without altering demyelination. These data are the first to demonstrate glia cell type-dependent B7-H1 regulation in vivo, resulting in adverse effects on antiviral CD8 T cell function. However, the beneficial role of PD-1:B7-H1 interactions in limiting morbidity highlights the need to evaluate tissue-specific intervention strategies.

Neonatal death in mice lacking cardiotrophin-like cytokine is associated with multifocal neuronal hypoplasia.

Mice with null mutations of ciliary neurotrophic factor (Cntf) receptor alpha (Cntf-Ralpha), or cytokine-like factor 1 (Clf), one component of Cntf-II (a heterodimeric Cntf-Ralpha ligand), die as neonates from motor neuron loss affecting the facial nucleus and ventral horn of the lumbar spinal cord. Exposure to cardiotrophin-like cytokine (Clc), the other putative Cntf-II element, supports motor neuron survival in vitro and in ovo. Confirmation that Clc ablation induces an equivalent phenotype to Clf deletion would support a role for Clc in the functional Cntf-II complex. In this study, Clc knockout mice had decreased facial motility, did not suckle, died within 24 hours, and had 32% and 29% fewer motor neurons in the facial nucleus and lumbar ventral horn, respectively; thus, Clc is essential for motor neuron survival during development. The concordance of the Clc knockout phenotype with those of mice lacking Cntf-Ralpha or Clf bolsters the hypothesis that Clc participates in Cntf-II.

Lesions in the central nervous system associated with perinatal lamb mortality.

OBJECTIVE: To identify and describe the occurrence of neurological lesions that could have an effect on lamb mortality. PROCEDURE: The central nervous system was investigated macroscopically (n = 92) and microscopically (n = 72) in lambs dying in the perinatal period during 3 years in flocks of adult Corriedale ewes. The central nervous system was removed intact and samples of cerebral cortex, basal ganglia, thalamus, hippocampus, mesencephalon, cerebellar cortex, medulla oblongata, and cervical spinal cord were scored microscopically for the severity of neuronal dead, cytotoxic and perivascular oedema, and haemorrhage. RESULTS: Neurologic findings between birth and 6 days included haemorrhages in meninges, brain congestion and oedema, neuronal ischemic necrosis, intraparenchymal haemorrhages in medulla oblongata and cervical spinal cord, parasagittal cerebral necrosis, and periventricular leukomalacia. No significant lesions were found in anteparturient deaths or in those aged between 7 and 16 days. Oedema was more severe in the brain than in other regions of the central nervous system. Ischaemic neurons first appeared 24 hours post partum, increased linearly in number between 48 hours and 5 days post partum, and had a laminar distribution in the cerebral cortex, indicating a hypoxic-ischemic encephalopathy. Haemorrhages were most severe in the gray matter of medulla oblongata and cervical spinal cord, suggesting trauma due to instability of atlantoaxialis joint. CONCLUSION: Lesions in the central nervous system can explain most deaths at birth and within 6 days of birth. The lesions were hypoxic-ischemic and appeared to be related to birth injury.

Outcomes in patients admitted for rehabilitation with spinal cord or cauda equina lesions following degenerative spinal stenosis.

PURPOSE: To evaluate outcome measures and the factors affecting them in patients treated between 1962 and 2000 at Loewenstein Rehabilitation Hospital, Israel. METHOD: This retrospective cohort study included 262 patients with spinal neurological lesions (spinal cord or cauda equina lesions) following degenerative spinal stenosis. Data were collected retrospectively. Survival was assessed using the Kaplan-Meier method and the relative mortality risk by the Cox model. Neurological recovery was evaluated by the change in Frankel grades, and factors that affect it were assessed by logistic regression. Associations of length of stay in rehabilitation were analyzed with ANOVA. RESULTS: Median age at lesion onset was 61 years and median survival 17.6 years. Age at spinal neurological lesion onset was found to be the only factor with a significant effect on survival. Of the 148 patients who had Frankel grades A, B, or C on admission, 58% achieved recovery to grades D and E. Frankel grade at admission, age, and spinal neurological level had a significant effect on recovery. The mean length of stay was 99.7 days, and only Frankel grade had a significant effect on length of stay. CONCLUSIONS: Patients with spinal stenosis and disabling spinal neurological lesions can achieve significant neurological recovery and survive for many years. They require adequate care in a specialist rehabilitation system.