European Multicenter Study About Spinal Cord Injury Research Articles

The revised zone of partial preservation (ZPP) in the 2019 International Standards for Neurological Classification of Spinal Cord Injury: ZPP applicability in incomplete injuries

Study designConsensus process.ObjectivesTo provide a reference for the Zone(s) of Partial Preservation (ZPP) in the 2019 International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) and analyze the initial impact of applicability of the revised ZPPs. Revisions include the use of ZPPs in selected incomplete injuries (in addition to prior use in sensorimotor complete injuries). Specifically, the revised motor ZPPs are applicable bilaterally in injuries with absent voluntary anal contraction (VAC) and the revised sensory ZPP for a given side is applicable if deep anal pressure (DAP), light touch and pin prick sensation in S4-5 are absent on that side.SettingCommittee with 16 ISNCSCI experts and datasets from the European Multicenter Study about Spinal Cord Injury (EMSCI).MethodsOccurrence frequencies of applicable ZPPs were determined in an EMSCI cohort consisting of two ISNCSCI examinations from 665 individuals with traumatic SCI.ResultsMotor ZPPs were derived in 35.2% of all datasets of incomplete injuries, while sensory ZPPs are much less frequent (1.0%). Motor ZPPs are applicable in all American Spinal Injury Association Impairment Scale (AIS) B datasets (mean ZPP length: 0.9 ± 1.0 segments), in 55.4% of all AIS C datasets (ZPP length: 11.8 ± 8.2 segments) and in 9.9% of the AIS D datasets (ZPP length: 15.4 ± 7.9 segments).ConclusionsThe revised ZPP allows for determining motor ZPPs in approximately 1/3 of all incomplete injuries. The broadened applicability enables the use of ZPPs beyond complete injuries for complementary description of residual functions in more individuals.SponsorshipN/A

Importance of Prospective Registries and Clinical Research Networks in the Evolution of Spinal Cord Injury Care.

Only 100 years ago, traumatic spinal cord injury (SCI) was commonly lethal. Today, most people who sustain SCI survive with continual efforts to improve their quality of life and neurological outcomes. SCI epidemiology is changing as preventative interventions reduce injuries in younger individuals, and there is an increased incidence of incomplete injuries in aging populations. Early treatment has become more intensive with decompressive surgery and proactive interventions to improve spinal cord perfusion. Accurate data, including specialized outcome measures, are crucial to understanding the impact of epidemiological and treatment trends. Dedicated SCI clinical research and data networks and registries have been established in the United States, Canada, Europe, and several other countries. We review four registry networks: the North American Clinical Trials Network (NACTN) SCI Registry, the National Spinal Cord Injury Model Systems (SCIMS) Database, the Rick Hansen SCI Registry (RHSCIR), and the European Multi-Center Study about Spinal Cord Injury (EMSCI). We compare the registries' focuses, data platforms, advanced analytics use, and impacts. We also describe how registries' data can be combined with electronic health records (EHRs) or shared using federated analysis to protect registrants' identities. These registries have identified changes in epidemiology, recovery patterns, complication incidence, and the impact of practice changes such as early decompression. They've also revealed latent disease-modifying factors, helped develop clinical trial stratification models, and served as matched control groups in clinical trials. Advancing SCI clinical science for personalized medicine requires advanced analytical techniques, including machine learning, counterfactual analysis, and the creation of digital twins. Registries and other data sources help drive innovation in SCI clinical science.

Computer International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) algorithms: a review

Study designLiterature review and survey.ObjectivesTo provide an overview of existing computerized International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) algorithms and to evaluate the use of the current algorithms in research and clinical care.SettingNot applicable.MethodsLiterature review according to three organizing concepts for evaluation of Health Information Products (reach, usefulness, and use) was conducted.ResultsWhile the use of computerized ISNCSCI algorithms has been around for many years, many were developed and used internally for specific projects or not maintained. Today the International SCI community has free access to algorithms from the European Multicenter Study about Spinal Cord Injury (EMSCI) and the Praxis Spinal Cord Institute. Both algorithms have been validated in large datasets and are used in different SCI registries for quality control and education purposes. The use of the Praxis Institute algorithm by clinicians was highlighted through the Praxis User Survey (n = 76) which included participants from 27 countries. The survey found that over half of the participants using the algorithm (N = 69) did so on a regular basis (51%), with 54% having incorporated it into their regular workflow.ConclusionsValidated computerized ISNCSCI classification tools have evolved substantially and support education, clinical documentation, communication between clinicians and their patients, and ISNCSCI data quality around the world. They are not intended to replace well-trained clinicians, but allow for reclassification of ISNCSCI datasets with updated versions of the ISCNSCI, and support rapid classification of large datasets.

International surveillance study in acute spinal cord injury confirms viability of multinational clinical trials

BackgroundThe epidemiological international landscape of traumatic spinal cord injury (SCI) has evolved over the last decades along with given inherent differences in acute care and rehabilitation across countries and jurisdictions. However, to what extent these differences may influence neurological and functional recovery as well as the integrity of international trials is unclear. The latter also relates to historical clinical data that are exploited to inform clinical trial design and as potential comparative data.MethodsEpidemiological and clinical data of individuals with traumatic and ischemic SCI enrolled in the European Multi-Center Study about Spinal Cord Injury (EMSCI) were analyzed. Mixed-effect models were employed to account for the longitudinal nature of the data, efficiently handle missing data, and adjust for covariates. The primary outcomes comprised demographics/injury characteristics and standard scores to quantify neurological (i.e., motor and sensory scores examined according to the International Standards for the Neurological Classification of Spinal Cord Injury) and functional recovery (walking function). We externally validated our findings leveraging data from a completed North American landmark clinical trial.ResultsA total of 4601 patients with acute SCI were included. Over the course of 20 years, the ratio of male to female patients remained stable at 3:1, while the distribution of age at injury significantly shifted from unimodal (2001/02) to bimodal distribution (2019). The proportional distribution of injury severities and levels remained stable with the largest percentages of motor complete injuries. Both, the rate and pattern of neurological and functional recovery, remained unchanged throughout the surveillance period despite the increasing age at injury. The findings related to recovery profiles were confirmed by an external validation cohort (n=791). Lastly, we built an open-access and online surveillance platform (“Neurosurveillance”) to interactively exploit the study results and beyond.ConclusionsDespite some epidemiological changes and considerable advances in clinical management and rehabilitation, the neurological and functional recovery following SCI has remained stable over the last two decades. Our study, including a newly created open-access and online surveillance tool, constitutes an unparalleled resource to inform clinical practice and implementation of forthcoming clinical trials targeting neural repair and plasticity in acute spinal cord injury.

Implementation of multilingual support of the European Multicenter Study about Spinal Cord Injury (EMSCI) ISNCSCI calculator

ObjectivesSince their introduction, electronic International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) calculators have evolved to powerful tools providing error-free ISNCSCI classifications in education, research and clinical practice. For increased accessibility and dissemination, a multilingual support is mandatory. The aim of this work was to setup a general multilingual framework for the freely available ISNCSCI calculator (https://ais.emsci.org) of the European Multicenter Study about Spinal Cord Injury (EMSCI).MethodsThe graphical user interface (GUI) and PDF export of the ISNCSCI worksheet were adapted for multilingual implementations. Their language-dependent content was identified. These two steps called internationalization have to be performed by a programmer in preparation of the translations of the English terms into the target language. This step following the internationalization is called localization and needs input by a bi-lingual clinical expert. Two EMSCI partners provided Standard Mandarin Chinese and Czech translations. Finally, the translations are made available in the application.ResultsThe GUI and PDF export of the ISNCSCI worksheet were internationalized. The default language of the calculator is set according to the user’s preferences with the additional possibility for manual language selection. The Chinese as well as a Czech translation were provided freely to the SCI community.ConclusionsThe possibility of multilingual implementations independent from software developers opens the use of ISNCSCI computer algorithms as an efficient training tool on a larger scale.

Long term outcome of functional independence and quality of life after traumatic SCI in Germany

Study designMulticenter observational study.ObjectiveTo describe the long-term outcome of functional independence and quality of life (QoL) for individuals with traumatic and ischemic SCI beyond the first year after injury.SettingA multicenter study in Germany.MethodsParticipants of the European multicenter study about spinal cord injury (EMSCI) of three German SCI centers were included and followed over time by the German spinal cord injury cohort study (GerSCI). Individuals’ most recent spinal cord independence measure (SCIM) scores assessed by a clinician were followed up by a self-report (SCIM-SR) and correlated to selected items of the WHO short survey of quality of life (WHO-QoL-BREF).ResultsData for 359 individuals were obtained. The average time passed the last clinical SCIM examination was 81.47 (SD 51.70) months. In total, 187 of the 359 received questionnaires contained a completely evaluable SCIM-SR. SCIM scores remained stable with the exception of reported management of bladder and bowel resulting in a slight decrease of SCIM-SR of −2.45 points (SD 16.81). SCIM-SR scores showed a significant correlation with the selected items of the WHO-QoL-BREF (p < 0.01) with moderate to strong influence.ConclusionSCIM score stability over time suggests a successful transfer of acquired independence skills obtained during primary rehabilitation into the community setting paralleled by positively related QoL measurements but bladder and bowel management may need special attention.

External Validation Confirms Validity of a Simple Model to Predict Bowel Outcome After Traumatic Spinal Cord Injury

Background. The prediction of functional outcomes after spinal cord injury (SCI) is essential to plan the rehabilitation phase and the social reintegration. Recently, 2 models to predict independent and reliable bowel management 1 year after traumatic SCI have been derived and validated in 2 cohorts of patients included in the European Multicenter Study about Spinal Cord Injury (EMSCI). Objective. We aimed to validate 2 prediction models for bowel outcome after traumatic SCI in a patient sample external to EMSCI. Methods. The simplified model (based on a single predictor, the International Standards for Neurological Classification of Spinal Cord Injury [ISNCSCI] total motor score) and the full model (based on 2 predictors, the ISNCSCI total motor score and item 3a of the Spinal Cord Independence Measure) were applied to the retrospectively collected data of 111 patients with traumatic SCI. Results. The simplified and the full models showed excellent discrimination with an area under the receiver operating characteristic curve of .939 (95% confidence interval (CI) .87-1.00) and .922 (95% CI 0.85-.99), respectively. Both models displayed similar results for sensitivity and negative predictive values; however, the simplified model showed higher values for specificity, positive predictive values, and accuracy. The calibration analysis showed a partial overlap between predicted probabilities and observed proportion, with better and acceptable calibration for the simplified model. Conclusions. Using an independent sample, our study demonstrates the validity of a simple model to predict independent and reliable bowel management 1 year after traumatic SCI.

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Canadian Spine SocietyPresentation CPSS1: Spinal insufficiency fracture in the geriatric pediatric spinePresentation CPSS2: The clinical significance of tether breakages in anterior vertebral body growth modulation: a 2-year postoperative analysisPresentation CPSS3: Anterior vertebral body growth modulation for idiopathic scoliosis: early, mid-term and late complicationsPresentation CPSS4: Ovine model of congenital chest wall and spine deformity with alterations of respiratory mechanics: follow-up from

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

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 < 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). 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.

Natural history of neurological improvement following complete (AIS A) thoracic spinal cord injury across three registries to guide acute clinical trial design and interpretation

Study designRetrospective, longitudinal analysis of motor and sensory outcomes following thoracic (T2–T12) sensorimotor complete spinal cord injury (SCI) in selected patients enrolled into three SCI) registries.ObjectivesTo establish a modern-day international benchmark for neurological recovery following traumatic complete thoracic sensorimotor SCI in a population similar to those enrolled in acute clinical trials.SettingAffiliates of the North American Clinical Trial Network (NACTN), European Multicenter Study about Spinal Cord Injury (EMSCI), and the Spinal Cord Injury Model Systems (SCIMS).MethodsOnly traumatic thoracic injured patients between 2006 and 2016 meeting commonly used clinical trial inclusion/exclusion criteria such as: age 16–70, T2–T12 neurological level of injury (NLI), ASIA Impairment Scale (AIS) A, non-penetrating injury, acute neurological exam within 7 days of injury, and follow-up neurological exam at least ~ 6 months post injury, were included in this analysis. International Standards for Neurological Classification of Spinal Cord injury outcomes including AIS conversion rate, NLI, and sensory and motor scores/levels were compiled.ResultsA total of 170 patients were included from the three registries: 12 from NACTN, 64 from EMSCI, and 94 from SCIMS. AIS conversion rates at approximately 6 months post injury varied from 16.7% to 23.4% (21.1% weighted average). Improved conversion rates were observed in all registries for low thoracic (T10–T12) injuries when compared with high/mid thoracic (T2–T9) injuries. The NLI was generally stable and lower extremity motor score (LEMS) improvement was uncommon and usually limited to low thoracic injuries only.ConclusionsThis study presents the aggregation of selected multinational natural history recovery data in thoracic AIS A patients from three SCI registries and demonstrates comparable minimal improvement of ISNCSCI-scored motor and sensory function following these injuries, whereas conversions to higher AIS grades occur at a frequency of ~20%. These data inform the development of future clinical trial protocols in this important patient population for the interpretation of the safety and potential clinical benefit of new therapies, and the potential applicability in a multinational setting.SponsorshipInVivo Therapeutics.

Ulnar nerve integrity predicts 1-year outcome in cervical spinal cord injury

BackgroundAccurate predictors of neurological recovery after cervical spinal cord injury are needed. Particularly, to tailor adequate rehabilitation plans. However, objective and quantifiable predictors are sparse.MethodsWithin the prospective European Multicenter Study about Spinal Cord Injury (EMSCI) registry, cervical spinal cord injury patients are monitored at fixed follow up visits (2, 4, 12, 24, and 48 weeks after injury) clinically and with ulnar nerve electroneurography. Associations of ulnar nerve compound muscle action potential amplitudes (CMAP) with American Spinal Cord Injury Association (ASIA) impairment scale (AIS) grades over time were analyzed using linear mixed modeling. Applying logistic regression, the prognostic value of within 4-week ulnar nerve CMAP for 1-year AIS was analyzed. To account for missing data, (1) last observation carried forward and (2) multiple imputation methods were applied. For model derivation, our centers’ cohort (EMSCI-HD) was analyzed. For model validation the cohort of other centers (EMSCI-nonHD) was used.ResultsIn the EMSCI-HD cohort, the median age (interquartile range (IQR)) was 52 (34–67) years. 58% were male. The initial AIS distribution was: A = 31%, B = 17%, C = 30%, and D = 22%). In the EMSCI-nonHD cohort, the median age was 49 (32–65) years. Compared to the EMSCI-HD cohort more patients were male (79%, p = 0.0034). The AIS distribution was: A = 33%, B = 13%, C = 21%, and D = 33%).In complete-case mixed model analyses (EMSCI-HD: n = 114; EMSCI-nonHD: n = 508) higher ulnar nerve CMAP were associated with better AIS grades over the entire follow up period. In complete-case logistic regression (EMSCI-HD: n = 90; EMSCI-nonHD: n = 444) higher ulnar nerve CMAP was an independent predictor of better AIS grades. The odds ratio for within 4-week ulnar nerve CMAP to predict 1-year AIS grade D versus A-C in the EMSCI-HD cohort was 1.24 per millivolt (confidence interval 1.07–1.44). The model was validated in an independent cervical spinal cord injury (EMSCI-nonHD) cohort (odds ratio 1.09, confidence interval 1.03–1.17).ConclusionsIn cervical spinal cord injury, the consideration of early ulnar nerve CMAP improves prognostic accuracy, which is of particular importance in patients with clinical grading uncertainties.

Progression of Neuropathic Pain after Acute Spinal Cord Injury: A Meta-Analysis and Framework for Clinical Trials.

The translation of therapeutic interventions to humans with spinal cord injury with the goal of promoting growth and repair in the central nervous system could, inadvertently, drive mechanisms associated with the development of neuropathic pain. A framework is needed to evaluate the probability that a therapeutic intervention for acute spinal cord injury modifies the progression of neuropathic pain. We analyzed a large, longitudinal dataset from the European Multi-Center Study about Spinal Cord Injury (EMSCI) and compared these observations with a previously published Swedish/Danish cohort. A meta-analysis was performed to produce aggregate estimates for the transition period between 1-6 months and the transition period between 1-12 months after injury. A secondary analysis used logistic regression to explore associations between the progression of neuropathic pain and demographics, pain characteristics, and injury characteristics. For overall neuropathic pain, 72% presenting with pain symptoms at one month reported persisting symptoms at six months, and 23% who did not have neuropathic pain at one month later had it develop. From 1-12 months, there was a similar likelihood of pain persisting (69%) and slightly higher rate of pain developing (36%). Characteristics that were significantly associated with the progression of pain included age and sensory and motor preservation. We provide historical benchmarks for estimating the progression of neuropathic pain during the first year after acute SCI. This information will be useful for comparison and evaluating safety during early phase acute spinal cord injury trials.

Prediction of bladder outcomes after ischemic spinal cord injury: A longitudinal cohort study from the European multicenter study about spinal cord injury.

The recovery of bladder function after spinal cord injury (SCI) is of major importance for patients and caregivers. We recently developed prediction models of bladder outcomes (defined as the capacity of storing the urine and emptying completely the bladder) 1 year after a SCI of traumatic etiology and investigated if these models would also be applicable to patients with ischemic SCI. From the European multicenter study about spinal cord injury (EMSCI), we extracted data of all ischemic SCI patients with available neurological and functional data (according to the International Standards for Neurological Classification of Spinal Cord Injury, ISNCSCI, and Spinal Cord Independence Measure, SCIM) within 40 days and bladder outcomes 1 year after ischemia. The model relies on three predictors: strength of the legs, the presence of sensation in the S3 dermatome, and the part of the SCIM assessing breathing and bladder and bowel control. A simplified model relying on leg strength only was also tested. Bladder outcomes were evaluated according to the score of item six of SCIM. In total 85 patients (56 males (66%), mean age 55 years) were included. Twenty-three patients (27%) showed complete bladder function recovery one year after ischemia. Both models showed a very good predictive power: the area under the receiver operating characteristics curve (aROC) of the two models was 0.825 and 0.822, respectively. Comparable to acute traumatic SCI, also in ischemic SCI the outcome of full bladder function recovery can be predicted by clinical scores, and prediction models of bladder outcomes may be applicable in clinical trials.

Volitional Voiding of the Bladder after Spinal Cord Injury: Validation of Bilateral Lower Extremity Motor Function as a Key Predictor

In many individuals with spinal cord injury a return of volitional bladder voiding is considered more important than regaining motor function. Recently a predictive model using only composite bilateral lower extremity motor scores for levels L2-S1 (range 0 to 50) was proposed by the EMSCI (European Multicenter Study about Spinal Cord Injury) group. The model showed exceptional predictive power with an AUC of 0.912. We sought to further validate the EMSCI model in a national spinal cord injury cohort. We created models of volitional voiding using the United States NSCID (National Spinal Cord Injury Database) for 2007 to 2016. In addition to testing lower extremity motor scores, we evaluated other patient variables that we hypothesized might affect volitional voiding. Volitional voiding was present in 1,333 of the cohort of 4,327 individuals (30.8%) at 1-year followup. While younger age, female gender, increased sacral sparing, improved AIS (American Spinal Injury Association Impairment Scale) classification and a more caudal sensory level predicted volitional voiding, lower extremity motor scores were most predictive (AUC 0.919). Adding the other patient characteristics did little to improve model performance (full model AUC 0.932). Further analysis of the predictive power of lower extremity motor scores suggested that while the AUC appeared to decrease in persons who were most likely to void volitionally, the performance of the predictive model remained outstanding with a combined AIS C and D AUC of 0.792. Our study verifies the validity of the EMSCI predictive model of volitional voiding after spinal cord injury. The differing performance of lower extremity motor scores in various AIS classifications should be noted.

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.

Toward Inclusive Trial Protocols in Heterogeneous Neurological Disorders

Background. Several novel drug- and cell-based potential therapies for spinal cord injury (SCI) have either been applied or will be considered for future clinical trials. Limitations on the number of eligible patients require trials be undertaken in a highly efficient and effective manner. However, this is particularly challenging when people living with incomplete SCI (iSCI) represent a very heterogeneous population in terms of recovery patterns and can improve spontaneously over the first year after injury. Objective. The current study addresses 2 requirements for designing SCI trials: first, enrollment of as many eligible participants as possible; second, refined stratification of participants into homogeneous cohorts from a heterogeneous iSCI population. Methods. This is a retrospective, longitudinal analysis of prospectively collected SCI data from the European Multicenter study about Spinal Cord Injury (EMSCI). We applied conditional inference trees to provide a prediction-based stratification algorithm that could be used to generate decision rules for the appropriate inclusion of iSCI participants to a trial. Results. Based on baseline clinical assessments and a defined subsequent clinical endpoint, conditional inference trees partitioned iSCI participants into more homogeneous groups with regard to the illustrative endpoint, upper extremity motor score. Assuming a continuous endpoint, the conditional inference tree was validated both internally as well as externally, providing stable and generalizable results. Conclusion. The application of conditional inference trees is feasible for iSCI participants and provides easily implementable, prediction-based decision rules for inclusion and stratification. This algorithm could be utilized to model various trial endpoints and outcome thresholds.

Identifying Homogeneous Subgroups in Neurological Disorders

Background. The reliable stratification of homogeneous subgroups and the prediction of future clinical outcomes within heterogeneous neurological disorders is a particularly challenging task. Nonetheless, it is essential for the implementation of targeted care and effective therapeutic interventions. Objective. This study was designed to assess the value of a recently developed regression tool from the family of unbiased recursive partitioning methods in comparison to established statistical approaches (eg, linear and logistic regression) for predicting clinical endpoints and for prospective patients’ stratification for clinical trials. Methods. A retrospective, longitudinal analysis of prospectively collected neurological data from the European Multicenter study about Spinal Cord Injury (EMSCI) network was undertaken on C4-C6 cervical sensorimotor complete subjects. Predictors were based on a broad set of early (<2 weeks) clinical assessments. Endpoints were based on later clinical examinations of upper extremity motor scores and recovery of motor levels, at 6 and 12 months, respectively. Prediction accuracy for each statistical analysis was quantified by resampling techniques. Results. For all settings, overlapping confidence intervals indicated similar prediction accuracy of unbiased recursive partitioning to established statistical approaches. In addition, unbiased recursive partitioning provided a direct way of identification of more homogeneous subgroups. The partitioning is carried out in a data-driven manner, independently from a priori decisions or predefined thresholds. Conclusion. Unbiased recursive partitioning techniques may improve prediction of future clinical endpoints and the planning of future SCI clinical trials by providing easily implementable, data-driven rationales for early patient stratification based on simple decision rules and clinical read-outs.

Spinal cord injury: association with axonal peripheral neuropathy in severely paralysed limbs

Pressure sores are a major health problem in spinal cord injury (SCI). In this population pressure damage to peripheral nerves was not thoroughly investigated so far. However, intact peripheral nerves and innervated muscles are a prerequisite for the effectiveness of supportive therapies like functional electrical stimulation (FES). We assessed electroneurographic (ENG) data of lower limbs in SCI individuals admitted to our hospital due to severe pressure sores. Our centers prospectively acquired ENG data of the European Multicenter study about SCI (EMSCI) patients served as early control. In the pressure sore cohort (n = 15) all patients were sensory-motor complete (American Spinal Cord Injury Association Impairment Scale A). Most patients (10/15) suffered from a severe axonal sensory-motor polyneuropathy in paralysed legs with absent compound muscle action potentials (CMAPs) of tibial/peroneal nerves as well as absent sensory nerve action potentials of sural nerves. The onset of this polyneuropathy dates within the first year after incident SCI and was mainly associated with increasing sensory-motor completeness as demonstrated by a significant CMAP drop of our centers EMSCI-ENG data on serial tibial nerve recordings in 275 patients. Severe SCI is associated with an early-onset axonal polyneuropathy in paralysed limbs to which pressure damage might contribute. Because intact peripheral nerves are required for: (i) maintenance of motor function in centrally impaired muscles; and (ii) effectiveness of supportive therapies like FES, ENG-monitoring could serve as a low invasive screening method for peripheral nerve integrity in patients with SCI to initiate pressure relief procedures early enough.

Relationship Between Motor Recovery and Independence After Sensorimotor-Complete Cervical Spinal Cord Injury

Background. For therapeutics directed to the injured spinal cord, a change in neurological impairment has been proposed as a relevant acute clinical study end point. However, changes in neurological function, even if statistically significant, may not be associated with a functional impact, such as a meaningful improvement in items within the self-care subscore of the Spinal Cord Independence Measure (SCIM). Objective. The authors examined the functional significance associated with spontaneously recovering upper-extremity motor function after sensorimotor-complete cervical spinal cord injury (SCI). Methods. Using the European Multi-center Study about Spinal Cord Injury (EMSCI) data set, a retrospective analysis was undertaken of individuals with cervical sensorimotor-complete SCI (initial motor level, C4-C7). Specifically, changes in upper-extremity motor score (UEMS), motor level, and SCIM (total and self-care subscore) were assessed between approximately 1 and 48 weeks after injury (n = 74). Results. The initial motor level did not significantly influence the total UEMS recovered or number of motor levels recovered. SCIM self-care subscore recovery was significantly greater for those individuals regaining 2 motor levels compared with those recovering only 1 or no motor levels. However, the recovery in the SCIM self-care subscore was not significantly different between individuals recovering only 1 motor level and those individuals who showed no motor-level improvement. Conclusions. A 2 motor-level improvement indicates a clinically meaningful change and might be considered a primary outcome in acute and subacute interventional trials enrolling individuals with cervical sensorimotor-complete SCI.

Characterization of neurological recovery following traumatic sensorimotor complete thoracic spinal cord injury

Retrospective, longitudinal analysis of sensory, motor and functional outcomes from individuals with thoracic (T2-T12) sensorimotor complete spinal cord injury (SCI). To characterize neurological changes over the first year after traumatic thoracic sensorimotor complete SCI. A dataset of 399 thoracic complete SCI subjects from the European Multi-center study about SCI (EMSCI) was examined for neurological level, sensory levels and sensory scores (pin-prick and light touch), lower extremity motor score (LEMS), ASIA Impairment Scale (AIS) grade, and Spinal Cord Independence Measure (SCIM) over the first year after SCI. AIS grade conversions were limited. Sensory scores exhibited minimal mean change, but high variability in both rostral and caudal directions. Pin-prick and light touch sensory levels, as well as neurological level, exhibited minor changes (improvement or deterioration), but most subjects remained within one segment of their initial injury level after 1 year. Recovery of LEMS occurred predominantly in subjects with low thoracic SCI. The sensory zone of partial preservation (ZPP) had no prognostic value for subsequent recovery of sensory levels or LEMS. However, after mid or low thoracic SCI, ≥3 segments of sensory ZPP correlated with an increased likelihood for AIS grade conversion. The data suggest that a sustained deterioration of three or more thoracic sensory levels or loss of upper extremity motor function are rare events and may be useful for tracking the safety of a therapeutic intervention in early phase acute SCI clinical trials, if a significant proportion of study subjects exhibit such an ascent.