[Movement analysis in spinal cord injuries : Assistance in clinical decision making]. / Bewegungsanalyse bei Querschnittverletzungen : Hilfestellung in der klinischen Entscheidungsfindung.

For motor incomplete spinal cord injured patients, improvement of walking function is an important aim in the rehabilitation program. In specialized treatment centers, the 6­minute walking test, the 10-meter walking test or the timed-up-and-go test are used as an assessment tool to determine walking ability, but these tests are not able to assess the quality of gait. Marker-based movement analysis can be used as a reliable method to evaluate the gait pattern. This allows an objective assessment of gait quality over time or can be used to support therapy planning. The benefit of such an analysis is presented by means of two case studies.

Immobility-associated thromboprotection is conserved across mammalian species from bear to human.

Venous thromboembolism (VTE) comprising deep venous thrombosis and pulmonary embolism is a major cause of morbidity and mortality. Short-term immobility-related conditions are a major risk factor for the development of VTE. Paradoxically, long-term immobilized free-ranging hibernating brown bears and paralyzed spinal cord injury (SCI) patients are protected from VTE. We aimed to identify mechanisms of immobility-associated VTE protection in a cross-species approach. Mass spectrometry-based proteomics revealed an antithrombotic signature in platelets of hibernating brown bears with heat shock protein 47 (HSP47) as the most substantially reduced protein. HSP47 down-regulation or ablation attenuated immune cell activation and neutrophil extracellular trap formation, contributing to thromboprotection in bears, SCI patients, and mice. This cross-species conserved platelet signature may give rise to antithrombotic therapeutics and prognostic markers beyond immobility-associated VTE.

A Predictive Model to Identify Treatment-related Risk Factors for Odontoid Fracture Nonunion Using Machine Learning.

STUDY DESIGN: Multicenter retrospective analysis of routinely collected data. OBJECTIVE: The underlying aim of this study was to identify potential treatment-related risk factors for odontoid fracture nonunion while accounting for known patient- and injury-related risk factors. SUMMARY OF BACKGROUND DATA: Type II and III odontoid fractures represent the most common cervical spine fracture in elderly patients and are associated with a relatively high nonunion rate. The management of odontoid fractures is controversial and treatment strategies range from conservative treatment to extensive surgical stabilization and fusion. METHODS: A total of 415 individuals who sustained odontoid fracture and were treated in either of four tertiary referral centers in Austria and Germany were included in the study. We included the following potential contributing factors for fracture nonunion in cross-validated extreme gradient boosted (XGBoost) and binary logistic regression models: age, gender, fracture displacement, mechanism of injury (high vs. low energy), fracture classification (Anderson II vs. III), presence of comorbidities (Charlson comorbidity index), and treatment (conservative, anterior screw fixation with one or two screws, posterior C1/C2 spondylodesis, cervico-occipital C0-C4 fusion). RESULTS: In our cohort, 187 (45%) had radiologically confirmed odontoid nonunion six months postinjury. The odds for nonunion increase significantly with age, and are lower in type III compared to type II fractures. Also, odds for nonunion are significantly lower in posterior C1/C2 spondylodesis, and C0-C4 fusion compared to conservative treatment. Importantly, odds are not statistically significantly lower in the group treated with anterior screw fixation compared to conservative treatment. The factors gender, fracture displacement, mechanism of injury, and the presence of comorbidities did not produce significant odds. CONCLUSION: Higher age, type II fractures, and conservative treatment are the main risk factors for odontoid nonunion. Anterior screw fixation did not differ significantly from conservative treatment in terms of fracture union. LEVEL OF EVIDENCE: 3.

Trajectory of Serum Levels of Glial Fibrillary Acidic Protein Within Four Weeks Post-Injury Is Related to Neurological Recovery During the Transition from Acute to Chronic Spinal Cord Injury.

The use of biomarkers in spinal cord injury (SCI) research has evolved rapidly in recent years whereby most studies focused on the acute post-injury phase. Since SCI is characterized by persisting neurological impairments, the question arises whether blood biomarkers remain altered during the subacute post-injury time. Sample collection in the subacute phase might provide a better insight in the ongoing SCI specific molecular mechanism with fewer confounding factors compared with the acute phase where, amongst other complications, individuals receive a substantial amount of medication. This study aimed to determine if the temporal dynamics of serum biomarkers of neurodegeneration differ between individuals depending on their extent of neurological recovery in the transition phase between acute and chronic SCI. We performed a secondary analysis of biomarkers in patients with SCI (n = 41) who were treated at a level I trauma center in Germany. Patients with cervical or thoracic SCI regardless of injury severity were included. Blood samples were collected in the acute phase (1-4 days post-injury), and after 30 and 120 days post-injury. Serum protein levels of glial fibrillary acidic protein (GFAP) and neurofilament light protein (NfL) were determined for each time-point of sample collection using R-Plex Assays (Meso Scale Discovery). Linear mixed models were used to evaluate the trajectory of GFAP and NfL over time. Fixed effects of time, neurological recovery, and injury severity, along with the recovery-by-time interaction, were included in models with random slopes and intercepts. GFAP levels increase during the first days after SCI and decrease in subacute to chronic stages. Notably, the trajectory of GFAP over time is significantly associated with the extent of neurological recovery during the transition from acute to chronic SCI with a steeper decline in individuals who recovered better. Serum levels of NfL continue to rise significantly until Day 30 followed by a decrease afterwards, independent of neurological recovery. The trajectory of serum GFAP levels qualifies as a prognostic biomarker for neurological recovery, and facilitates monitoring of disease progression in the sub-acute post-injury phase.

Systemic Immune Profile Predicts the Development of Infections in Patients with Spinal Cord Injuries.

Patients with spinal cord injury (SCI) frequently develop infections that may affect quality of life, be life-threatening, and impair their neurological recovery in the acute and subacute injury phases. Therefore, identifying patients with SCI at risk for developing infections in this stage is of utmost importance. We determined the systemic levels of immune cell populations, cytokines, chemokines, and growth factors in 81 patients with traumatic SCI at 4 weeks after injury and compared them with those of 26 age-matched healthy control subjects. Patients who developed infections between 4 and 16 weeks after injury exhibited higher numbers of neutrophils and eosinophils, as well as lower numbers of lymphocytes and eotaxin-1 (CCL11) levels. Accordingly, lasso logistic regression showed that incomplete lesions (American Spinal Injury Association Impairment Scale [AIS] C and D grades), the levels of eotaxin-1, and the number of lymphocytes, basophils, and monocytes are predictive of lower odds for infections. On the other hand, the number of neutrophils and eosinophils as well as, in a lesser extent, the levels of IP-10 (CXCL10), MCP-1 (CCL2), BDNF [brain-derived neurotrophic factor], and vascular endothelial growth factor [VEGF]-A, are predictors of increased susceptibility for developing infections. Overall, our results point to systemic immune disbalance after SCI as predictors of infection in a period when infections may greatly interfere with neurological and functional recovery and suggest new pathways and players to further explore novel therapeutic strategies.

A New Score Based on the International Standards for Neurological Classification of Spinal Cord Injury for Integrative Evaluation of Changes in Sensorimotor Functions.

Sensorimotor function of patients with spinal cord injury (SCI) is commonly assessed according to the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). From the ISNCSCI segmental motor and sensory assessments, upper and lower extremity motor scores (UEMS and LEMS), sum scores of pinprick (PP) and light touch (LT) sensation, the neurological level of injury (NLI) and the classification of lesion severity according to the American Spinal Injury Association Impairment Scale (AIS) grade are derived. Changes of these parameters over time are used widely to evaluate neurological recovery. Evaluating recovery based on a single ISNCSCI scoring or classification variable, however, may misestimate overall recovery. Here, we propose an Integrated Neurological Change Score (INCS) based on the combination of normalized changes between two time points of UEMS, LEMS, and total PP and LT scores. To assess the agreement of INCS with clinical judgment of meaningfulness of neurological changes, changes of ISNCSCI variables between two time points of 88 patients from an independent cohort were rated by 20 clinical experts according to a five-categories Likert Scale. As for individual ISNCSCI variables, neurological change measured by INCS is associated with severity (AIS grade), age, and time since injury, but INCS better reflects clinical judgment about meaningfulness of neurological changes than individual ISNCSCI variables. In addition, INCS is related to changes in functional independence measured by the Spinal Cord Independence Measure (SCIM) in patients with tetraplegia. The INCS may be a useful measure of overall neurological change in clinical studies.

Serum Levels of Glial Fibrillary Acidic Protein and Neurofilament Light Protein Are Related to the Neurological Impairment and Spinal Edema after Traumatic Spinal Cord Injury.

Neurological examination in the acute phase after spinal cord injury (SCI) is often impossible and severely confounded by pharmacological sedation or concomitant injuries. Therefore, diagnostic biomarkers that objectively characterize severity or the presence of SCI are urgently needed to facilitate clinical decision-making. This study aimed to determine if serum markers of neural origin are related to: 1) presence and severity of SCI, and 2) magnetic resonance imaging (MRI) parameters in the very acute post-injury phase. We performed a secondary analysis of serological parameters, as well as MRI findings in patients with acute SCI (n = 38). Blood samples were collected between Days 1-4 post-injury. Serum protein levels of glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), and neurofilament light protein (NfL) were determined. A group of 41 age- and sex-matched healthy individuals served as control group. In the group of individuals with SCI, pre-operative sagittal and axial T2-weighted and sagittal T1-weighted MRI scans were available for 21 patients. Serum markers of neural origin are different among individuals who sustained traumatic SCI depending on injury severity, and the extent of the lesion according to MRI in the acute injury phase. Unbiased Recursive Partitioning regression with Conditional Inference Trees (URP-CTREE) produced preliminary cut-off values for NfL (75.217 pg/mL) and GFAP (73.121 pg/mL), allowing a differentiation between individuals with SCI and healthy controls within the first 4 days after SCI. Serum proteins NfL and GFAP qualify as diagnostic biomarkers for the presence and severity of SCI in the acute post-injury phase, where the reliability of clinical exams is limited.

Natural Progression of Routine Laboratory Markers after Spinal Trauma: A Longitudinal, Multi-Cohort Study.

Our objective was to track and quantify the natural course of serological markers over the 1st year following spinal cord injury. For that purpose, data on serological markers, demographics, and injury characteristics were extracted from medical records of a clinical trial (Sygen) and an ongoing observational cohort study (Murnau study). The primary outcomes were concentration/levels/amount of commonly collected serological markers at multiple time points. Two-way analysis of variance (ANOVA) and mixed-effects regression techniques were used to account for the longitudinal data and adjust for potential confounders. Trajectories of serological markers contained in both data sources were compared using the slope of progression. Our results show that, at baseline (≤ 2 weeks post-injury), most serological markers were at pathological levels, but returned to normal values over the course of 6-12 months post-injury. The baseline levels and longitudinal trajectories were dependent on injury severity. More complete injuries were associated with more pathological values (e.g., hematocrit, ANOVA test; χ2 = 68.93, df = 3, adjusted p value <0.001, and χ2 = 73.80, df = 3, adjusted p value <0.001, in the Sygen and Murnau studies, respectively). Comparing the two databases revealed some differences in the serological markers, which are likely attributable to differences in study design, sample size, and standard of care. We conclude that because of trauma-induced physiological perturbations, serological markers undergo marked changes over the course of recovery, from initial pathological levels that normalize within a year. The findings from this study are important, as they provide a benchmark for clinical decision making and prospective clinical trials. All results can be interactively explored on the Haemosurveillance web site (https://jutzelec.shinyapps.io/Haemosurveillance/) and GitHub repository (https://github.com/jutzca/Systemic-effects-of-Spinal-Cord-Injury).

Association of timing of gabapentinoid use with motor recovery after spinal cord injury.

OBJECTIVE: To explore the hypothesis that earlier administration of acute gabapentinoids is beneficial to motor recovery after spinal cord injury in humans. METHODS: This is an observational study using a cohort from the European Multi-Centre Study about Spinal Cord Injury. Patient charts were reviewed to extract information regarding the administration and timing of gabapentinoid anticonvulsants. The primary outcome measure was motor scores, as measured by the International Standards for Neurological Classification of Spinal Cord Injury, collected longitudinally in the first year after injury. Sensory scores (light touch and pinprick) and functional measures (Spinal Cord Independence Measure) were secondary outcomes. Linear mixed effects regression models included a drug-by-time interaction to determine whether exposure to gabapentinoids altered recovery of muscle strength in the first year after injury. RESULTS: A total of 201 participants were included in the study and had a median age of 46 and baseline motor score of 50. Participants were mostly men (85%) with sensory and motor complete injuries (50%). Seventy individuals (35%) were administered gabapentinoids within the first 30 days after injury, and presented with similar demographics. In the longitudinal model, the administration of gabapentinoids within 30 days after injury was associated with improved motor recovery when compared to those who did not receive gabapentinoids during this time (3.69 additional motor points from 4 to 48 weeks after injury; p = 0.03). This effect size increased as administration occurred earlier after injury (i.e., a benefit of 4.68 points when administered within 5 days). CONCLUSIONS: This retrospective, observational study provided evidence of the beneficial effect of gabapentinoid anticonvulsants on motor recovery after spinal cord injury. More critically, it highlighted a potential time dependence, suggesting that earlier intervention is associated with better outcomes. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that gabapentinoids improve motor recovery for individuals with acute spinal cord injury.

Severe pressure ulcers requiring surgery impair the functional outcome after acute spinal cord injury.

STUDY DESIGN: Retrospective matched cohort study. OBJECTIVES: Assessing the influence of surgically managed grade 3 and 4 pressure ulcers (PU) in the acute phase after spinal cord injury (SCI) on the neurological and functional outcome after 1 year. SETTING: Specialized SCI-unit within a level 1 trauma center in Murnau, Germany. METHODS: We performed a retrospective matched cohort study. For every patient with acute SCI and a PU requiring surgery, we identified matched controls within our database in a 1:3 ratio. Matching criteria were: AIS-grade (American Spinal Injury Association Impairment Scale), neurological level and age. The scores of the SCIM-III (Spinal Cord Independence Measure) and the ISNCSCI (International Standards for Neurological Classification of Spinal Cord Injury) as well as the total length of stay (LOS) at the hospital were used as outcome parameters. We applied a stratified analysis using a conditional logistic regression to test for group differences in each outcome parameter of the study. RESULTS: In a 6-year period (2010-2015) 28 patients required flap surgery due to 3-4° PU in the acute phase after SCI. Of these patients, 15 had complete data sets according to the EMSCI (European Multicenter Study about Spinal Cord Injury) protocol. Patients with severe PUs during the acute SCI phase had a significantly impaired functional outcome. After 1 year the improvement of the SCIM score was significantly lower in the PU group compared to the control group (17.4 versus 30.5; p < 0.006). However, the change in AIS grade after 1 year was not significantly affected. The LOS was prolonged by a mean of 48 days in the PU group (p < 0.006). CONCLUSIONS: Severe PUs requiring surgery in the acute phase after SCI impair the functional outcome and increase LOS. Preventive measures should be applied to all acute SCI patients. Patients should be transferred to specialized SCI-centers as soon as possible.

Early Decompression (<8 Hours) Improves Functional Bladder Outcome and Mobility After Traumatic Thoracic Spinal Cord Injury.

BACKGROUND: There is accumulating evidence of a potential beneficial effect of early surgical intervention after acute cervical spinal cord injury (SCI). However, around one third of all SCIs affect the thoracic spine. This cohort has not been extensively investigated, mainly because of less sensitive clinical readout measures. Apart from regaining full sensorimotor function, improvements in bladder and bowel management remain of the highest priority for patients with chronic paraplegia. Therefore, this study investigates the effect of early decompression (here defined as <8 hours) versus delayed management on neurologic and functional outcome. METHODS: We retrospectively analyzed data from the institutional database, in which follow-up data were collected prospectively according to the European Multicenter Study about Spinal Cord Injury standards. Within a 13-year period, we identified 43 patients who met inclusion and exclusion criteria. Of these, 32 (74%) were managed surgically within the first 8 hours. There was a trend toward a higher rate of patients with clinically complete SCI in the early group at baseline. RESULTS: After 1 year, we did not observe a benefit on the neurologic outcome as assessed via the American Spinal Injury Association Impairment Scale grade. Functional outcome was evaluated using the Spinal Cord Independence Measure (SCIM). The early decompressed group demonstrated significantly improved SCIM 6 (i.e., bladder management) (P < 0.045) and SCIM 9-11 subitems (i.e., mobility, transfer) (P < 0.019). CONCLUSIONS: Early decompression was an independent predictor for improved functional bladder outcome and mobility after 1 year. This effect needs to be studied in future prospective, multicenter studies.

Earlier Decompression (< 8 Hours) Results in Better Neurological and Functional Outcome after Traumatic Thoracolumbar Spinal Cord Injury.

The optimal timing of surgical intervention following spinal cord injury (SCI) remains under debate. Recent studies indicate a potential neurological and functional benefit of early surgery (< 8 h) after cervical SCI. For thoracolumbar SCI syndromes, fewer studies exist. Bladder and bowel dysfunction are highly relevant for these patients and impair their quality of life. Hence, we performed a retrospective study on patients with thoracolumbar SCI who were operated on at our institution and who met inclusion as well as exclusion criteria (n = 58 patients). Follow-up data were collected prospectively within a fixed time schedule over 1 year according to the European Multicenter Study about Spinal Cord Injury protocol. Early decompression was defined as within the first 8 h after injury and was performed in 35 patients. After the follow-up period, the early decompression group showed improved American Spinal Injury Association Impairment Scale (AIS) grades (p < 0.040) and a higher AIS conversion (p < 0.021). Further, these patients demonstrated a higher total Spinal Cord Independence Measure (SCIM) difference (p < 0.005). Special emphasis was placed on the functional bladder and bowel outcome. Here, we observed improved bladder outcome (i.e., SCIM-6 sub-item; p < 0.021) and a trend towards better functional bowel management (i.e., SCIM-7; p < 0.090). Linear regression models showed that early surgery was an independent predictor for higher AIS shifts and improved total SCIM difference. Our data suggests that prompt surgical management after thoracolumbar SCI might have a positive impact on the functional and neurological outcome.

Functional outcome after traumatic cervical spinal cord injury is superior in adolescents compared to adults.

OBJECTIVE: Determining differences in neurological and functional outcome between adolescents and adults after acute traumatic spinal cord injury (SCI). DESIGN: Retrospective, multi-center case-control study. METHODS: 100 cases of patients under 18 years at accident with acute traumatic cervical SCI admitted to SCI centers participating in the European Multi-center study about SCI (EMSCI) between January 2005 and April 2016 were reviewed. According to their age at accident, age 13 to 17, patients were selected for the adolescent group. After applying in- and exclusion criteria 32 adolescents were included. Each adolescent patient was matched with two adult SCI patients for analysis. OUTCOME MEASURES: ASIA Impairment scale (AIS) grade, neurological, sensory, motor level, total motor score, and Spinal Cord Independence Measure (SCIM III) total score. RESULTS: Mean AIS conversion, neurological, motor and sensory levels as well as total motor score showed no significantly statistical difference in adolescents compared to the adult control group after follow up of 6 months. Significantly higher final SCIM scores (p < 0.05) in the adolescent group compared to adults as well as a strong trend for a higher gain in SCIM score (p < 0.061) between first and last follow up was found. CONCLUSIONS: Neurological outcome after traumatic cervical SCI is not superior in adolescents compared to adults in this cohort. Significantly higher SCIM scores indicate more functional gain for the adolescent patients after traumatic cervical SCI. Juvenile age appears to be an independent predictor for a better functional outcome.

Elevated Autoantibodies in Subacute Human Spinal Cord Injury Are Naturally Occurring Antibodies.

Spinal cord injury (SCI) results in long-term neurological and systemic consequences, including antibody-mediated autoimmunity, which has been related to impaired functional recovery. Here we show that autoantibodies that increase at the subacute phase of human SCI, 1 month after lesion, are already present in healthy subjects and directed against non-native proteins rarely present in the normal spinal cord. The increase of these autoantibodies is a fast phenomenon-their levels are already elevated before 5 days after lesion-characteristic of secondary immune responses, further supporting their origin as natural antibodies. By proteomics studies we have identified that the increased autoantibodies are directed against 16 different nervous system and systemic self-antigens related to changes known to occur after SCI, including alterations in neural cell cytoskeleton, metabolism and bone remodeling. Overall, in the context of previous studies, our results offer an explanation to why autoimmunity develops after SCI and identify novel targets involved in SCI pathology that warrant further investigation.

Effectiveness of Automated Locomotor Training in Patients with Acute Incomplete Spinal Cord Injury: A Randomized, Controlled, Multicenter Trial.

The aim of this study was to evaluate whether the effect of longer training times (50 instead of 25 min per day) using a robotic device results in a better outcome of walking ability of subjects with a subacute motor complete (American Spinal Injury Association Impairment Scale [AIS]-B) and incomplete (AIS-C) spinal cord injury. Twenty-one patients were enrolled in the study, whereof 18 completed, on average, 34 trainings in 8 weeks. Longer training times resulted in better locomotor function. The second important result of the study is that a beneficial effect can be achieved by the application of a robotic device for prolonged training sessions without requiring more personal resources. It has to remain open whether even longer training times (more than 50 min) would result in a still better outcome. In any case, the extent of possible recovery in an individual patient is determined by the level and severity of spinal cord damage.

Early Decompression (< 8 h) after Traumatic Cervical Spinal Cord Injury Improves Functional Outcome as Assessed by Spinal Cord Independence Measure after One Year.

There is an ongoing controversy about the optimal timing for surgical decompression after acute traumatic cervical spinal cord injury (SCI). For this reason, we performed a retrospective study of patients who were operated on after traumatic cervical SCI at the Trauma Center Murnau, Germany, and who met inclusion as well as exclusion criteria (n = 70 patients). Follow-up data were collected prospectively according to the European Multicenter Study about Spinal Cord Injury (EMSCI) protocol over a period of 1 year. Early decompression was defined as within the first 8 h after the insult (n = 35 patients). Primary outcome was the difference in the SCIM (Spinal Cord Independence Measure) 1 year after the trauma. After the follow-up period, patients who were decompressed earlier had a significantly higher SCIM difference (45.8 vs. 27.1, p < 0.005). A regression analysis showed that timing of decompression, age, as well as basal AIS (American Spinal Injury Association Impairment Scale) and basal SCIM scores were independent predictors for a better functional outcome (SCIM). Further, patients from the early decompression group had better AIS grades (p < 0.006) and a higher AIS conversion rate (p < 0.029). Additionally, this cohort also had a better total motor performance as well as upper extremity motor function after 1 year (p < 0.025 and p < 0.002). The motor and neurological levels of patients who were operated on within 8 h were significantly more caudal (p < 0.003 and p < 0.014) after 1 year. The present study suggests that early decompression after traumatic cervical SCI might have a positive impact on the functional and neurological outcome of affected individuals.

Charcot spinal arthropathy: an increasing long-term sequel after spinal cord injury with no straightforward management.

Charcot spinal arthropathy (CSA) is most likely increasing in patients suffering from consequences of spinal cord injury. We want to highlight initial symptoms, certain risk factors and perioperative complications of this condition. A single center retrospective case series in a specialized Center for Spinal Cord Injuries, BG Trauma Center Murnau, Germany highlighting the potential obstacles in the management of Charcot spine. We describe four female paraplegic patients (mean age: 50.75 years; range: 42-67), who developed Charcot spinal arthropathies. The mean age at the time of the accident was 21.5 years (3-35), the time lag after the accident before CSA was developed and finally diagnosed was on average 29.5 years (17-39) and the mean follow-up period was 39.5 months (6-73). Patient histories, initial symptoms, risk factors as well as the management and postoperative complications are provided. Charcot spine is an important potential sequel of spinal cord injury, which can lead to significant disability and spinal emergencies in affected individuals. More studies are needed to provide better recommendations for spine surgeons. Conservative treatment is an option. Posterior fixation alone does not seem to be sufficient.