Search

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 (

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.

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.

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 i) presence and severity of SCI, and ii) 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. 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 four 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.

Multicenter retrospective analysis of routinely collected data.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.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.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).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.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.3.

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.

ObjectiveTo explore the hypothesis that earlier administration of acute gabapentinoids is beneficial to motor recovery after spinal cord injury in humans.MethodsThis 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.ResultsA 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).ConclusionsThis 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.

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 as8 hours) versus delayed management on neurologic and functional outcome.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.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) (P0.045) and SCIM 9-11 subitems (i.e., mobility, transfer) (P0.019).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.

Retrospective matched cohort study. 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. Specialized SCI-unit within a level 1 trauma center in Murnau, Germany. 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. 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

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

ObjectiveTo track and quantify the natural course of hematological markers over the first year following spinal cord injury.MethodsData on hematological 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 hematological markers at multiple time-points. Two-way ANOVA and mixed-effects regression techniques were used to account for the longitudinal data and adjust for potential confounders. Trajectories of hematological markers contained in both data sources were compared using the slope of progression.ResultsAt baseline (≤ 2 weeks post-injury), most hematological markers were at pathological levels, but returned to normal values over the course of six to twelve 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; Chisq = 77.10, df = 3, adjusted p-valueConclusionsDue to trauma-induced physiological perturbations, hematological 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 website (https://jutzelec.shinyapps.io/Haemosurveillance/).Code availabilityhttps://github.com/jutzca/Systemic-effects-of-Spinal-Cord-Injury

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.

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 (

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

Determining differences in neurological and functional outcome between adolescents and adults after acute traumatic spinal cord injury (SCI).Retrospective, multi-center case-control study.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.ASIA Impairment scale (AIS) grade, neurological, sensory, motor level, total motor score, and Spinal Cord Independence Measure (SCIM III) total score.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.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.

Introduction De nombreuses etudes montrent que le reapprentissage de tâches motrices depend considerablement de l’intensite de l’entrainement. Dans le cadre hospitalier, un entrainement quotidien intensif reste un defi, entre autres pour des questions de frais de personnel. L’utilisation de nouvelles technologies peut completer ce potentiel de maniere complementaire. Cette etude a evalue si de plus longs temps d’entrainement (50 minutes par entrainement au lieu de 25 minutes) sont possibles et s’ils conduisent a une meilleure capacite a marcher. Methode Vingt et un patients atteints de paraplegie motrice non aigue complete (American Spinal Injury Association Impairment Scale [ASIA B]) et incomplete (ASIA C) ont ete inclus dans cette etude et repartis aleatoirement en un groupe d’entrainement standard (max. 25 minutes) ou intensif (au moins 50 minutes) avec un robot d’aide a la marche (Lokomat, Hocoma SA, Volketswil/CH). L’entrainements a dure 8 semaines et comprenait 3–5 entrainements par semaine. Resultats Dix-huit patients ont termine l’entrainement (moyenne 34 entrainements). Les entrainements plus longs sont significativement et clairement associes a une meilleure capacite a se deplacer (Spinal Cord Independence Measure, domaine de mobilite 20/40 vs 10/40). Aucun resultat indesirable n’a ete observe. Conclusions Les resultats valident l’hypothese selon laquelle un entrainement appuye par une technologie est possible et que des entrainements prolonges conduisent a de meilleurs resultats. Il n’a pas encore pu etre montre si des entrainements encore plus longs peuvent encore ameliorer ces resultats. Chez les patients examines, le retablissement des fonctions neurologiques et fonctionnelles depend de l’entrainement, mais aussi du niveau et de la gravite de la lesion de la moelle epiniere. Signification La mise a profit de l’ensemble du potentiel de readaptation doit etre consideree au moyen de formes d’entrainement assistees par des moyens technologiques.

During the first rehabilitation of patients with traumatic spinal cord injuries (SCIs), professional skills are learned, which can be objectified in an independent measurement score. The aims of this study were to record the skills of patients 12 and 48 weeks after acute trauma and perform an analysis of the data to identify provisions of importance.All patients from 2004 to 2009 who experienced traumatic SCI were included in this investigation. Data recording were accomplished by the European Multi-Centre Study about Spinal Cord Injury (EMSCI) databank. Patients were divided into tetraplegia and paraplegia groups. Parameters were age at injury, the American Spinal Injury Association-Score, level of lesion and spinal cord independence measure (SCIM-Score) 12 and 48 weeks after traumatic spinal cord lesion. A questionnaire was also added to help clarify where deficiencies were prevalent.Data analysis of 103 tetraplegic and 110 paraplegic patients showed no correlation between the ASIA score, level of lesion, age and SCIM score. On average, tetraplegic patients had a SCIM score of 43 points 12 weeks after treatment, with 81% showing an increase to 58 points after 48 weeks. Paraplegic patients showed an average SCIM score of 60 points after 12 weeks, with 71% experiencing an increase to 71 points after 48 weeks. In all, 9% of tetraplegic patients and 19% of paraplegic patients experienced a decrease of SCIM points after 48 weeks, which occurred mainly in the bladder and intestinal control subgroups. Results of the questionnaire were not helpful for clarifying the location of the deficiencies.Most of the patients experienced an increase of SCIM points 48 weeks after traumatic SCI. However, data also showed that, especially in paraplegic patients, special attention must be given to bladder and intestinal management to avoid negative late-term consequences.

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.

Background: A large proportion of patients with spinal cord injury (SCI) regain ambulatory function. However, during the first 3 months most patients are unable to walk without support. To enable ambulatory training at such an early stage the body weight is partially relieved and leg movement assisted by two therapists. A more recent approach is the application of robotic-based assistance, which allows for longer training duration. From the science of motor learning and studies including patients with stroke, it is known that training effects depend on the duration of the training. Longer training results in a better walking function. Purpose: The aim of the present study is to evaluate whether prolonged robot-assisted walking training leads to a better walking outcome in patients with incomplete SCI, who are initially unable to walk independently (i.e. B and C according to the International Standards for Neurological Classification of SCI-ISNCSCI), and whether such training is feasible or is associated with undesirable effects. Methods: Patients from three sites with an acute incomplete SCI (within 60 days after injury) were randomized to either standard training (session duration 25 minutes) or intensive training (session duration 50 minutes). After 8 weeks of training walking ability (Walking Index for SCI-WISCI, scale 0-20: 0=not able to walk, 20= able to walk independently), the occurrence of adverse events and the rate of perceived exertion (RPE, scale 1-10: 1=very light, 10= very, very hard), as well as patients’ global impression of change (PGIC, scale 0 -10: 0= much better, 5= no change, 10= much worse) were compared between groups. Results: Seventeen patients with incomplete SCI were randomly assigned either to standard training (ISNCSCI B: n=6; C: n=2) or to intensive training (B: n=3; C: n=6). The average duration of training of the standard group was half the length of the intensive group (24.9±0.6 minutes vs. 48.3±3.2 minutes; p=0.01). Both groups performed an equal number of training sessions within 8 weeks (33.8±6.8 and 34.9±6.0; n.s.). The median WISCI changed from 0 to 4 in the standard group (n.s.) and from 0 to 10.5 (p

IntroductionTraumatic cervical spinal cord injury affects the individual in a multi-faceted way. Early decompression of the spinal canal is recommended. The optimal time point for this intervention...