Aging with spinal cord injury: A narrative review of consequences and challenges.

Given the increase in life expectancy, aging with a pre-existing spinal cord injury (SCI) is becoming more common. This condition is challenging as compromised health status and functional independence can worsen. We aimed to provide an updated overview of the consequences of aging with SCI, highlighting the main challenges facing this population in a narrative review of the current literature we retrieved from the PubMed database from 2000 to 2022 on any aspect related to aging in persons with SCI. Here we address adverse circumstances that increase disability and hinder an active lifestyle, such as progressive physical deterioration, secondary health conditions, limitations in personal activity, changes in family and social support structures, aging of caregivers, and depletion of economic resources. Favorable changes are also observed, including psychosocial adjustments that improve quality of life. Additionally, various interventions are discussed to promote well-being, health, and social participation. Due to the relevance of this issue, people with SCI and all those who take care of them must have up-to-date information to carry out the necessary measures to promote healthy aging in a more inclusive social environment.

Immunization with neural-derived peptides increases neurogenesis in rats with chronic spinal cord injury.

AIMS: Immunization with neural-derived peptides (INDP) has demonstrated to be a promising therapy to achieve a regenerative effect in the chronic phase of the spinal cord injury (SCI). Nevertheless, INDP-induced neurogenic effects in the chronic stage of SCI have not been explored. METHODS AND RESULTS: In this study, we analyzed the effect of INDP on both motor and sensitive function recovery; afterward, we assessed neurogenesis and determined the production of cytokines (IL-4, IL-10, and TNF alpha) and neurotrophic factors (BDNF and GAP-43). During the chronic stage of SCI, rats subjected to INDP showed a significant increase in both motor and sensitive recovery when compared to the control group. Moreover, we found a significant increase in neurogenesis, mainly at the central canal and at both the dorsal and ventral horns of INDP-treated animals. Finally, INDP induced significant production of antiinflammatory and regeneration-associated proteins in the chronic stages of SCI. CONCLUSIONS: These findings suggest that INDP has a neurogenic effect that could improve motor and sensitive recovery in the chronic stage of SCI. Moreover, our results also envision the use of INDP as a possible therapeutic strategy for other trauma-related disorders like traumatic brain injury.

Single vs. Combined Therapeutic Approaches in Rats With Chronic Spinal Cord Injury.

The regenerative capability of the central nervous system is limited after traumatic spinal cord injury (SCI) due to intrinsic and extrinsic factors that inhibit spinal cord regeneration, resulting in deficient functional recovery. It has been shown that strategies, such as pre-degenerated peripheral nerve (PPN) grafts or the use of bone marrow stromal cells (BMSCs) or exogenous molecules, such as chondroitinase ABC (ChABC) promote axonal growth and remyelination, resulting in an improvement in locomotor function. These treatments have been primarily assessed in acute injury models. The aim of the present study is to evaluate the ability of several single and combined treatments in order to modify the course of chronic complete SCI in rats. A complete cord transection was performed at the T9 level. One month later, animals were divided into five groups: original injury only (control group), and original injury plus spinal cord re-transection to create a gap to accommodate BMSCs, PPN, PPN + BMSCs, and PPN + BMSCs + ChABC. In comparison with control and single-treatment groups (PPN and BMSCs), combined treatment groups (PPN + BMSCs and PPN + BMSCs + ChABC) showed significative axonal regrowth, as revealed by an increase in GAP-43 and MAP-1B expression in axonal fibers, which correlated with an improvement in locomotor function. In conclusion, the combined therapies tested here improve locomotor function by enhancing axonal regeneration in rats with chronic SCI. Further studies are warranted to refine this promising line of research for clinical purposes.

Creation of an intramedullary cavity by hemorrhagic necrosis removal 24 h after spinal cord contusion in rats for eventual intralesional implantation of restorative materials.

Intramedullary hemorrhagic necrosis occurs early after spinal cord injury at the site of injury and adjacent segments. It is considered harmful because of its potential to aggravate secondary injury, and to interfere with axonal regeneration; it might also lead to an unfavorable environment for intralesional implants. Removal of hemorrhagic necrosis has been attempted before with variable results. The invasive nature of these procedures carries the risk of exacerbating damage to the injured cord. The overall objective for this study was to test several strategies for non-damaging removal of hemorrhagic necrosis and characterize the resulting cavity looking for a space for future intralesional therapeutic implants in rats with acute cord injury. Rats were subjected to graded cord contusion, and hemorrhagic necrosis was removed after 24h. Three grades of myelotomy (extensive, medium sized, and small) were tested. Using the small surgical approach to debridement, early and late effects of the intervention were determined by histology and by analytical and behavioral analysis. Appearance and capacity of the resulting cavity were characterized. Satisfactory removal of hemorrhagic necrosis was achieved with all three surgical approaches to debridement. However, bleeding in spared cord tissue was excessive after medium sized and extensive myelotomies but similar to control injured rats after small cord surgery. Small surgical approach to debridement produced no swelling nor acute inflammation changes, nor did it affect long-term spontaneous locomotor recovery, but resulted in modest improvement of myelination in rats subjected to both moderate and severe injuries. Cavity created after intervention was filled with 10 to 15 µL of hydrogel. In conclusion, by small surgical approach to debridement, removal of hemorrhagic necrosis was achieved after acute cord contusion thereby creating intramedullary spaces without further damaging the injured spinal cord. Resulting cavities appear suitable for future intralesional placement of pro-reparative cells or other regenerative biomaterials in a clinically relevant model of spinal cord injury.

Temporal changes of spinal subarachnoid space patency after graded spinal cord injury in rats.

INTRODUCTION: Disturbances in spinal subarachnoid space (SSAS) patency after SCI have been reported as an incidental finding, but there is a lack of information on its in vivo extent and time course. For substances and cells carried in the cerebrospinal fluid (CSF) to reach damaged neural tissue and promote reparative processes, CSF must be able to flow freely in SASS. OBJECTIVE: To characterise the extent and time course of SSAS patency disruption in vivo in a rat model after graded SCI. MATERIALS AND METHODS: Anaesthetised rats were subjected to mild or severe cord contusion at T9. Estimation of SSAS patency was carried out at 1h and 1, 3, 7, 15, 30 and 90 days postinjury, as well as in naïve rats, by quantifying the passage of superparamagnetic beads injected into the CSF at the cisterna magna and recovered at spinal level L2. CSF volume recovery was measured simultaneously. Data were analysed by the two-way ANOVA test. RESULTS: Estimation of SSAS patency revealed nearly complete blockage early after contusion that was unevenly restored entering the chronic stages. Volume of CSF recovered was also significantly decreased early after injury compared to naïve rats, but was fully restored by 1 month postinjury. Overall, although modestly different from each other, changes in both parameters were more pronounced after severe rather than mild injuries for each time point examined. CONCLUSIONS: SCI alters SSAS patency. Its extent is a function primarily of time elapsed after lesion and secondly of injury severity. It is reasonable to expect that disturbances in SASS patency might alter CSF dynamics and impair self-reparative mechanisms and intrathecal therapeutics, making SSAS patency blockage a key target for SCI management.

Superparamagnetic beads for estimation of spinal subarachnoid space permeability in rats.

BACKGROUND: Human spinal pathological processes have been linked to a loss of spinal subarachnoid space (SSAS) permeability, which has therefore become a target for therapy. Hence, it has become important to measure SSAS patency in rat models of these human disorders. NEW METHOD: The estimation of in vivo rat SSAS patency is described by quantifying passage of streptavidin-covered superparamagnetic beads (SPMB) in cerebrospinal fluid (CSF). Beads are injected into the cisterna magna and recovered at spinal level L2. They are then coated with biotynilated horseradish peroxidase for enzymatically based colorimetric measurement, after removal of bloody CSF to avoid interference with the colorimetric readings. The procedure was tested in intact rats and in rats 24 h after T9 laminectomy. Residual beads in SSAS were viewed by histology. RESULTS: Average bead recovery from intact rats was 6.4% of amount initially administered, in a mean CSF volume of 126 µL; in laminectomized rats, it was 1%, in a mean CSF volume of 39.2 µL. COMPARISON WITH EXISTING METHOD(S): Unlike in vivo imaging techniques, such as myelography (used here to validate our method) and near infrared fluorescence technology for qualitative rat SSAS patency viewing, our SPMB-based method allows for an in vivo quantitative estimation of the permeability of this space. CONCLUSIONS: A novel method has been established to reliably determine SSAS permeability in rats. The method is reproducible and has the required sensitivity to detect an 84.4% reduction in bead recovery, as seen in laminectomized rats compared to intact animals.

Spatial and temporal morphological changes in the subarachnoid space after graded spinal cord contusion in the rat.

Spontaneous repair or treatment-induced recovery after spinal cord injury (SCI) is very limited and might be related to extramedullary alterations that have only briefly been documented. Here we report on the morphological changes of the spinal subarachnoid space (SAS) in a clinically relevant model of SCI. Anesthetized rats were subjected either to mild or severe spinal cord contusion at T9. Spine blocks from the site of injury and adjacent segments were harvested at acute (1 h and 1 day [d]), subacute (3 and 7 d), and chronic (1 and 3 months) stages post-injury. Histopathology and morphometry at each decalcified vertebral level were assessed. At acute and subacute stages, reduction of SAS lumen was observed after both mild and severe injuries. Acutely, after severe injuries, SAS occlusion was associated mainly with cord swelling and subarachnoid hematomas; a trend for dural sac constriction was observed for mild injuries. At 7 d, cord swelling diminished in both instances, but dural sac constriction increased for severe injuries. At early stages, in the epicenter and vicinity, histopathology revealed compression of neurovascular elements within the SAS, which was more intense in severe than in mild injuries. In the chronic stage, SAS lumen increased notably, mostly from cord atrophy, despite dural sac constriction. Myelograms complemented observations made on SAS lumen permeability. Post-traumatic arachnoiditis occurred mainly in animals with severe injury. In conclusion, early extramedullary SAS changes described here might be expected to produce alterations in cerebrospinal fluid (CSF) dynamics and cord blood perfusion, thereby contributing to the pathophysiology of SCI and becoming novel targets for treatment.

New approach for graded compression spinal cord injuries in Rhesus macaque: method feasibility and preliminary observations.

BACKGROUND: Current models of spinal cord injury (SCI) have been ineffective for translational research. Primate blunt SCI, which more closely resembles human injury, could be a promising model to fill this gap. METHODS: Graded compression SCI was produced by inflating at T9 an epidural balloon as a function of spinal canal dimensions in a non-uniform group of monkeys. RESULTS: Sham injury and cord compression by canal invasion of 50-75% produced minimal morpho-functional alterations, if at all. Canal invasion of 90-100% resulted in proportional functional deficits. Unexpectedly, these animals showed spontaneous gradual recovery over a 12-week period achieving quadruped walking, although with persistent absence of foot grasping reflex. Histopathology revealed predominance of central cord damage that correlated with functional status. CONCLUSIONS: Our preliminary results suggest that this model could potentially be a useful addition to translational work, but requires further validation by including animals with permanent injuries and expansion of replicates.

Early administration of L-arginine in experimental acute spinal cord injury impairs long-term motor function recovery.

BACKGROUND: Recently, we reported that L-arginine, a nitric oxide precursor, reverses altered drug disposition induced by acute spinal cord injury (SCI) by increasing hepatic blood flow, without affecting mean arterial pressure and heart rate, whereas others have shown that it produces neuroprotection in several models of acute neurologic damage. Its use as a therapeutic agent for microcirculatory alterations associated with spinal shock seems promising. Therefore, here we have tested its influence on long-term morphofunctional neurologic outcome. METHODS: Intravenous L-arginine (300 mg/kg per dose) was administered to adult rats after SCI of moderate intensity according to the following schemes (n=6): (1) single dose at 1 hour, (2) single dose at 24 hour, and (3) repeated doses first at 24 hour and then daily for 7 days. Control injured rats received the vehicle (saline solution). RESULTS: Contrary to our expectations, locomotor function, assessed using the Basso-Beattie-Bresnahan scale for 8 weeks, was significantly worse in the L-arginine treated groups compared with the control group. Areas of both spared white matter and myelin stain at the epicenter seemed reduced in rats that received L-arginine as a single dose at 1 hour after injury but were not significantly different from the control group. CONCLUSIONS: L-arginine as used here interfered with the functional outcome of rats subjected to SCI, suggesting that L-arginine or its metabolic products may be neurotoxic. Because of its potential utility for acute SCI suggested in the past, strategies should be designed to block its apparent neurotoxicity.

High doses of 4-aminopyridine improve functionality in chronic complete spinal cord injury patients with MRI evidence of cord continuity.

BACKGROUND AND AIMS: Many patients with complete spinal cord injury (SCI) exhibit demyelinated and poorly myelinated nerve fibers traversing the lesion site. Conventional doses of 4-aminopyridine (4-AP, 30 mg/day) have shown to provide no or minor functional improvement in these patients. We undertook this study to test the functional effect of high doses of 4-AP on patients with chronic complete SCI with cord continuity at the site of injury demonstrated by magnetic resonance imaging. METHODS: Fourteen patients were included in a double-blind, randomized, placebo-controlled trial followed by an open label long-term follow-up. Initially, patients received 4-AP or placebo orally, with 4-AP being increased gradually (5 mg/week) to reach 30 mg/day. For long-term treatment, 4-AP was increased 10 mg periodically according to negative electroencephalogram and blood test abnormalities and minor adverse reactions. Pre-treatment, 12 and 24 weeks of the controlled trial, and 6 and 12 months of open trial evaluations, or with the highest doses reached were obtained. RESULTS: Three of 12 patients were able to walk with the assistance of orthopedic devices, 1/12 became incomplete (AIS B), 7/12 improved their somatosensory evoked potentials, 5/12 had sensation and control of bladder and anal sphincters, and 4/9 male patients had psychogenic erection. CONCLUSIONS: Positive changes were seen mainly in patients with cyst (4/5) or atrophy (3/5) of the injury site. Two patients withdrew from the study: one had seizures and one had intolerant adverse reactions. We conclude that high doses of 4-AP in the studied population produced several functional benefits not observed using lower doses.

Diversity and commonalities in the care of spine trauma internationally.

STUDY DESIGN: Questionnaires administered to practicing orthopedic and neurosurgical spine surgeons from North America, Europe, Asia, Australia, and New Zealand. OBJECTIVE: To determine diversity and commonalities in the treatment of spine trauma internationally. SUMMARY OF BACKGROUND DATA: Previous studies have had suggested that there is significant variability in the treatment of common spinal trauma conditions. METHODS: Questionnaires based on 10 commonly encountered spine trauma cases were administered to 77 experienced spinal surgeons across 4 continents. The questions for each case scenario were similar, but were tailored to be appropriate for the case being presented. Questions focused on the discipline of the specialist who would treat the injury, the treatment itself, and how long it would take for the patient to return home or to work. Questions pertaining to investigations, funding, estimated in-hospital length of stay, prehospital care, and mortality were also included. Each question was followed by 4 to 8 options from which the surgeon could chose a response. Data were analyzed using, SAS v9.2, a software analytical package, to determine the level of agreement between respondents on different items. RESULTS: Of the 77 surgeons completing the questionnaire, 66% were fellowship trained spine surgeons, 20% orthopedic surgeons, and 14% neurosurgeons. In all regions, the majority of spinal trauma care is provided in a regional trauma center with dedicated spine surgeons. In all but 1 case significant differences were found in treatment with European and Asian surgeons have a higher operative rate. A combined anterior/posterior surgical approach was more commonly used in Europe and Asia. North American patients are expected to have a shorter hospital stay and return to work earlier. Significant differences exist between Asia and the other regions with regard to prehospital care. CONCLUSION: These findings suggest that despite the subspecialty focus in the care of spinal trauma, there continues to exist a lack of consensus among treating surgeons as to the optimum management and appropriateness of multiple aspects of specific operative and nonoperative interventions and indeed the postinjury management.

Stereolithography in spine pathology: a 2-case report.

BACKGROUND: Solid plastic replicas of anatomical structures obtained by stereolithography from computed tomographic images and magnetic resonance imaging are being used as complementary tools for diagnostic purposes and therapy planning for diverse pathologies. CASE DESCRIPTIONS: Case 1--The spine mold of a 62-year-old man with neurologic compromise secondary to degenerative cervical disease was used to study the pathologic features of his spine and to plan and simulate the approach to remove osteophytes before surgery. Also, by examining the replica of his spine, the unconvinced patient was able to understand the nature of his pathology and realize that his neurologic symptoms would disappear only through surgery, as they did. Case 2--A 27-year-old woman had uncontrolled back and leg pain possibly related to anxiety and depression. She had undergone one unsuccessful lumbo-sacral surgery and was now obsessed with the thought that her second surgery, performed by us, likewise had failed, even though her magnetic resonance images proved otherwise. It was not until she held a replica of her repaired spine in her hands that she was able to understand that her pain was unfounded. Once she was able to relax, her chronic pain and anxiety disappeared within a month, using the same antidepressive treatment that formerly had been ineffective. CONCLUSIONS: Spine replicas are useful devices for diagnosis, planning, and simulating surgery, and they enable patients to understand the nature of their pathologies and the surgical procedures at hand.

Thalidomide fails to be therapeutic following contusive spinal cord injury in rats.

Mechanical damage to the spinal cord (SC) generates self-destructive processes that contribute to post-traumatic neurodegeneration. Because thalidomide apparently counteracts these effects its use clinically has been proposed enthusiastically. Nonetheless, we tested its action as a neuroprotectant in a clinically relevant model of SC injury in rats. We administered thalidomide intraperitoneally to rats subjected to thoracic SC contusion as single or repeated doses within the first 24 h after injury. Edema, neutrophil infiltration, and cord tissue preservation/destruction were assessed in the SC 24 h after injury and motor function for 7 weeks. Rats treated with thalidomide showed significant increase in SC water compared with naive rats, but not vehicle-treated rats; their neutrophil infiltration and amount of spared/destroyed cord tissue was not different from vehicle-treated rats; and in no case was motor performance improved after thalidomide. In conclusion, thalidomide failed here to be therapeutic, discouraging its use clinically for SC trauma.

Clinical outcomes of 90 isolated unilateral facet fractures, subluxations, and dislocations treated surgically and nonoperatively.

STUDY DESIGN: A retrospective outcomes study. OBJECTIVE: The purposes of this study were 1) to identify plausible patient and interventional variables that influence the outcome of unilateral facet injuries and 2) to determine if patients return to normal general health status after unilateral facet injuries. SUMMARY OF BACKGROUND DATA: The management of unilateral subaxial cervical facet fractures and dislocations lacks agreement on treatment options and the variables that influence outcome. METHODS: Injury data, radiographs, and outcomes (North American Spine Society Cervical Follow-up Questionnaire and Short Form-36) were collected from 9 centers and 13 surgeons, members of the Spine Trauma Study Group. RESULTS: Causally motor vehicle accidents (49%) and sports (31%) predominated. The C6-C7 level accounted for 60% of injuries and C5-C6 represented 17%. The mean SF-36 PCS score of the operative patients with follow-up >18 months was 6.70 points higher than the mean of the nonoperative patients (P = 0.017). The SF-36 Bodily Pain mean of all patients was 67.2 (SD = 27.6), significantly lower (more pain) than the normative mean of 75.2 (SD = 23.7) (P = 0.014). Nonoperative patients also reported a mean Bodily Pain score of 63.0 (SD = 30.5) that was significantly worse than normative values (P = 0.031). Similarly, the NASS PD mean score for all patients was 84.8 (SD = 17.9), significantly lower than the normative mean of 89.1 (SD = 15.5) (P = 0.014). CONCLUSION: To our knowledge this is the largest reported series of facet injuries to date and the only one using health-related quality of life instruments. Unilateral facet injuries of the subaxial cervical spine led to reported levels of pain and disability that are significantly worse than those of the healthy population. Although further study is required, we suggest that nonoperatively treated patients report worse outcomes than operatively treated patients, particularly at longer follow-up despite having a more benign fracture pattern. The presence of comorbidities, associated injuries, and advanced age adversely impact clinical outcomes.

The subaxial cervical spine injury classification system: a novel approach to recognize the importance of morphology, neurology, and integrity of the disco-ligamentous complex.

STUDY DESIGN: The classification system was derived through a literature review and expert opinion of experienced spine surgeons. In addition, a multicenter reliability and validity study of the system was conducted on a collection of trauma cases. OBJECTIVES: To define a novel classification system for subaxial cervical spine trauma that conveys information about injury pattern, severity, treatment considerations, and prognosis. To evaluate reliability and validity of this system. SUMMARY OF BACKGROUND DATA: Classification of subaxial cervical spine injuries remains largely descriptive, lacking standardization and prognostic information. METHODS: Clinical and radiographic variables encountered in subaxial cervical trauma were identified by a working section of the Spine Trauma Study Group. Significant limitations of existing systems were defined and addressed within the new system. This system, as well as the Harris and Ferguson & Allen systems, was applied by 20 spine surgeons to 11 cervical trauma cases. Six weeks later, the cases were randomly reordered and again scored. Interrater reliability, intrarater reliability, and validity were assessed. RESULTS: Each of 3 main categories (injury morphology, disco-ligamentous complex, and neurologic status) identified as integrally important to injury classification was assigned a weighted score; the injury severity score was obtained by summing the scores from each category. Treatment options were assigned based on threshold values of the severity score. Interrater agreement as assessed by intraclass correlation coefficient of the DLC, morphology, and neurologic status scores was 0.49, 0.57, and 0.87, respectively. Intrarater agreement as assessed by intraclass correlation coefficient of the DLC, morphology, and neurologic status scores was 0.66, 0.75, and 0.90, respectively. Raters agreed with treatment recommendations of the algorithm in 93.3% of cases, suggesting high construct validity. The reliability compared favorably to the Harris and Ferguson & Allen systems. CONCLUSION: The Sub-axial Injury Classification and Severity Scale provides a comprehensive classification system for subaxial cervical trauma. Early validity and reliability data are encouraging.

A quantitative and reproducible method to assess cord compression and canal stenosis after cervical spine trauma: a study of interrater and intrarater reliability.

STUDY DESIGN: Reliability study. OBJECTIVE: To assess the intrarater and interrater reliability of a recently described technique to measure of maximum canal compromise (MCC) and maximum spinal cord compression (MSCC) using digitized and magnified images in the setting of traumatic cervical spinal cord injury (SCI). SUMMARY OF BACKGROUND DATA: The extent of MCC and MSCC is of clinical and prognostic value in the setting of traumatic cervical SCI. However, concerns remain regarding the accuracy of measurements based on hard copy images. We hypothesized that the interrater and intrarater reliability of these assessments would be enhanced using magnified digitized images and software-based measurement tools. METHODS: Midsagittal MRI and CT images of cervical spine were selected from 5 individuals with acute traumatic cervical SCI. Measurements of MCC using CT scan and T1-weighted MRI and measurements of MSCC based on T2-weighted MR images were independently estimated by 13 raters on 10 occasions. RESULTS: The intrarater reliability for CT-MCC, T1-weighted MRI-MCC and T2-weighted MRI-MSCC was high in the 10 rounds in each patient. In addition, the mean intrarater interclass correlation coefficient was 0.72 +/- 0.05 for the CT-MCC, 0.70 +/- 0.07 for the T1-weighted MRI-MCC, and 0.68 +/- 0.11 for the T2-weighted MRI-MSCC. The mean interrater interclass correlation coefficients were 0.43 +/- 0.02 for the CT-MCC, 0.61 +/- 0.03 for the T1-weighted MRI-MCC, and 0.55 +/- 0.05 for the evaluation of T2-weighted MRI-MSCC. CONCLUSION: Our study has demonstrated that the intrarater reliability for the instrument to assess MCC and MSCC in the setting of traumatic SCI was high. The interrater ICCs at a moderate level of reliability combined with our results using analysis of variance with post hoc tests indicate that the measurements of MCC and MSCC are reproducible, which supports the use of these radiologic parameters in the clinical and research settings.

Cyclosporin-A enhances non-functional axonal growing after complete spinal cord transection.

Therapeutic approaches that promote both neuroprotection and neuroregeneration would be valuable for spinal cord (SC) injury therapies. Cyclosporin-A (CsA) is an immunosuppressant that, due to its mechanism of action, could both protect and regenerate the neural tissue after injury. Previous studies have already demonstrated that intraperitoneal administration of CsA at a dose of 2.5 mg/kg/12 h during the first 2 days after SC contusion, followed by 5 mg/kg/12 h orally, diminishes tissue damage and improves motor recovery. In order to evaluate the effect of this CsA dosing regimen on axonal growth, we assessed motor recovery, presence of axons establishing functional connections and expression of GAP-43 in rats subjected to a complete SC transection. The Basso-Beattie-Bresnahan rating scale did not show difference in motor recovery of CsA or vehicle-treated rats. Moreover, somato-sensorial evoked potentials demonstrated no functional connections in the SC of these animals. Nevertheless, histological studies showed that: i) a significant number of CsA-treated rats presented growing axons, although they deviated perpendicularly at the edge of the stumps, surrounding them, ii) the expression of GAP-43 in animals treated with CsA was higher than that observed in the control group. Finally, anterograde tracing of the corticospinal tract of rats subjected to an incomplete SC transection showed no axonal fibers reaching the caudal stump. In summary, CsA administered at the dosing-regimen that promotes neuroprotection in SC contused rats induces both GAP-43 expression and axonal growth; however, it failed to generate functional connections in SC transected animals.

The adoption of a new classification system: time-dependent variation in interobserver reliability of the thoracolumbar injury severity score classification system.

STUDY DESIGN: Prospective clinical assessment of the interobserver reliability of the Thoracolumbar Injury Classification and Severity Score (TLISS) in a series of consecutive patients. OBJECTIVE: To evaluate the time-dependent changes in interobserver reliability of the TLISS system. SUMMARY OF BACKGROUND DATA: Reliability of an injury classification system is fundamental to its usefulness. A system that can be taught and implemented effectively will be highly reliable. Vaccaro et al recently introduced a novel thoracolumbar injury classification and treatment recommendation system called the "Thoracolumbar Injury Classification and Severity Score." An improvement over previous traumatic thoracolumbar systems, it has been designed to be both descriptive as well as prognostic. To define better the benefits of this system, the purpose of our study was to assess the time-dependent changes associated with implementation of the TLISS system at 1 institution. METHODS: Seventy-one consecutive patients presenting with acute thoracolumbar injury were prospectively assessed at a single training institution. Plain radiographs, computed tomography, and magnetic resonance imaging were independently reviewed, and each case was classified according to the TLISS system. Seven months later, 25 consecutive patients presenting with acute thoracolumbar injuries were prospectively assessed at the same institution. TLISS classification criteria were again applied after reviewing plain radiographs, computed tomography, and magnetic resonance imaging. The unweighted Cohen kappa coefficient and Spearman correlation values were calculated to assess interobserver reliability at each assessment time. Interobserved reliability at the time of the first assessment was then compared with interobserver reliability from the second assessment. RESULTS: Statistically significant (P < 0.05) improvements in interobserver reliability were observed. Both the unweighted Cohen kappa coefficient and Spearman correlation values increased across all comparable fields: TLISS subscores (mechanism of injury, posterior ligamentous complex), total TLISS, and TLISS management scores. CONCLUSIONS: The significant improvements observed in interobserver reliability of the TLISS system suggest that the classification system can be taught effectively and be readily incorporated into daily practice. The strong correlation values obtained at the second assessment time suggest that the TLISS system may be reproducibly used to describe thoracolumbar injuries.

Interobserver and intraobserver reliability of maximum canal compromise and spinal cord compression for evaluation of acute traumatic cervical spinal cord injury.

STUDY DESIGN: Prospective, blinded validation study of an objective, quantitative measure to assess maximum canal compromise (MCC) and maximum spinal cord compression (MSCC) in individuals with acute cervical spinal cord injury (SCI). OBJECTIVE: To examine the intraobserver and interobserver reliability of MCC and MSCC in individuals with acute traumatic cervical SCI. SUMMARY OF BACKGROUND DATA: To date, few quantitative reliable radiologic methods for assessing the extent of spinal cord compression in the setting of acute SCI have been reported. MCC and MSCC, as assessed on mid-sagittal CT and T2-weighted MR images, respectively, appear to have potential clinical and prognostic value. To date, the validation of these assessment tools has been limited to a small number of observers at a single institution. However, to date no study has focused on the reliability of these radiologic parameters among a large cohort of spine surgeons from North America and abroad. This type of validation is critical to allow the broader use of these outcome measures in research studies and in clinical practice. METHODS: Mid-sagittal MRI and CT images of cervical spine were selected from 10 individuals with acute traumatic cervical SCI. A total of 28 spine surgeons independently estimated CT MCC, T1-weighted MRI MCC, and T2-weighted MRI MSCC on two occasions using a calibrated ruler. In the first round of measurements, the observers estimated the radiologic parameters using only written instructions. The second measurement set was obtained after an interactive teaching session on the methodology. The order of the images was altered for the second set of measurements. RESULTS: Analysis using parametric and nonparametric statistics indicated high intraobserver reliability for CT MCC, T1-weighted MRI MCC, and T2-weighted MSCC with interclass correlation coefficients (ICCs) of 0.92, 0.95, and 0.97, respectively. The interobserver reliability for all three radiologic parameters was considered moderate with ICCs ranging from 0.35 to 0.56. CONCLUSION: Our results indicate that the intraobserver reliability for the MCC and MSCC was high. Although the interobserver reliability for all three radiologic parameters in the present study was below 0.75, the observed differences were small and largely accounted for by the limitations in the precision of the calibrated ruler. For cases with minimal cord compression, the measurement of canal stenosis (MCC) proved more accurate. In contrast, in cases with severe cord compression, the assessment of MSCC was more accurate. It is anticipated that the use of digital imaging technologies will further enhance the precision of these outcome measures.