Nerve Transfer After Cervical Spinal Cord Injury: Who Has a "Time Sensitive" Injury Based on Electrodiagnostic Findings?

OBJECTIVE: To use the ulnar compound muscle action potential (CMAP) to abductor digiti minimi (ADM) to identify the proportion of individuals with cervical spinal cord injury (SCI) who have lower motor neuron (LMN) abnormalities involving the C8-T1 spinal nerve roots, within 3-6 months, and thus may influence the response to nerve transfer surgery. DESIGN: Retrospective analysis of prospectively collected data. Data were analyzed from European Multicenter Study About SCI database. SETTING: Multi-center, academic hospitals. PARTICIPANTS: We included 79 subjects (age=41.4±17.7, range:16-75; 59 men; N=79), who were classified as cervical level injuries 2 weeks after injury and who had manual muscle strength examinations that would warrant consideration for nerve transfer (C5≥4, C8<3). INTERVENTIONS: None. MAIN OUTCOME MEASURES: The ulnar nerve CMAP amplitude to ADM was used as a proxy measure for C8-T1 spinal segment health. CMAP amplitude was stratified into very abnormal (<1.0 mV), sub-normal (1.0-5.9 mV), and normal (>6.0 mV). Analysis took place at 3 (n=148 limbs) and 6 months (n=145 limbs). RESULTS: At 3- and 6-month post-injury, 33.1% and 28.3% of limbs had very abnormal CMAP amplitudes, respectively, while in 54.1% and 51.7%, CMAPs were sub-normal. Median change in amplitude from 3 to 6 months was 0.0 mV for very abnormal and 1.0 mV for subnormal groups. A 3-month ulnar CMAP <1 mV had a positive predictive value of 0.73 (95% CI 0.69-0.76) and 0.78 (95% CI 0.75-0.80) for C8 and T1 muscle strength of 0 vs 1 or 2. CONCLUSION: A high proportion of individuals have ulnar CMAPs below the lower limit of normal 3- and 6-month post cervical SCI and may also have intercurrent LMN injury. Failure to identify individuals with LMN denervation could result in a lost opportunity to improve hand function through timely nerve transfer surgeries.

Sitting Pressure Measurements in Wheelchair Users-Can the Effects of Daily Relief Activities Be Depicted?

Seat pressure measurements in wheelchair users have been available for some time; however, repeated measurements from a commercially available pressure mat over 90 min did not differ in the pressure-loaded measurement area or the coordinates of the center of pressure, even in participants who were able to reposition themselves in the wheelchair. The question therefore arises: to what extent are there other parameters that reflect the activity of wheelchair users with the pressure mat? To investigate this, a commercial pressure mat (BodiTrak®) was used to perform the measurements of pressure of 33 adult wheelchair-dependent people with spinal cord injury after 30 and 90 min sitting on the cushion. In addition to the standard output of the pressure mat, graph-based surface analyses (calculation of the area of maximum pressure, calculation of the pressure-loaded measurement area, and pressure-area ratio) was performed retrospectively using Python 3.7. The analysis of the measurements after 30 and 90 min was performed by distinguishing the participants between those who could actively change their position (N = 24) and those who could not (N = 9). The parameters of the pressure mat and the graph-based analyses remained unchanged for active participants. In participants who were unable to actively change their position, the area of maximum pressure and the pressure-area ratio (ratio of maximum pressure area and total pressure-loaded area) increased. Significant differences between minutes 30 and 90 are only found for the pressure-area ratio. Thus, when measuring the seat pressure of wheelchair users, the pressure-area ratio should be taken into account as it reflects the daily relief activities of wheelchair users.

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

BACKGROUND: The 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. METHODS: Epidemiological 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. RESULTS: A 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. CONCLUSIONS: Despite 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.

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

STUDY DESIGN: Multicenter observational study. OBJECTIVE: To 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. SETTING: A multicenter study in Germany. METHODS: Participants 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). RESULTS: Data 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. CONCLUSION: SCIM 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.

Which factors have an association to the Quality of Life (QoL) of people with acquired Spinal Cord Injury (SCI)? A cross-sectional explorative observational study.

STUDY DESIGN: Cross-sectional explorative observational study. OBJECTIVES: To identify factors which have an association to the self-perceived Quality of Life (QoL) for persons with acquired spinal cord injury (SCI). SETTING: Eight specialized SCI-centers in Germany. The GerSCI survey is the German part of the International Spinal Cord Injury Survey (InSCI). METHODS: Self-disclosure questionnaire, created from the InSCI group, translated and adapted for Germany. The questionnaire collects a very broad range of data and, and due to its design as a self-report, is particularly suitable for the analysis on QoL. Because of the content, which is binding for all participating states, it allows a direct comparability of the results. Included in Germany were 1479 persons with acquired SCI aged 18 years and older. RESULTS: Various factors were identified with high associations to QoL, including changeable and unchangeable ones, such as those of particular importance: pain, sleep problems, sexual dysfunction, age, and time since onset of SCI. Some results confirmed reports of previous studies, others were surprising. CONCLUSION: this study provides an important basis for the planned analysis of the InSCI participating countries in the 6 WHO regions. Germany was able to contribute the largest study population. The concrete study design of InSCI allows us to directly compare data and helps us to improve ourselves within the framework of a "learning health system". Medical measures can be orientated towards the found results, in order to ensure the best possible care and support by the therapeutic team, individually adapted to the person, place of residence and impairment.

Development and validation of a simplified thoracolumbar spine fracture classification system.

STUDY DESIGN: Development and validation of fracture classification system. OBJECTIVE: To develop and validate a Simplified Classification System (SCS) for Thoraco-Lumbar (TL) fractures (SCS - TL fractures). SETTING: Tertiary Spinal Injuries Centre, New Delhi, India METHODS: Based on the International Spinal Cord Society Spine Trauma Study Group (ISCoS STSG, n = 23) experts' clinical consensus conducted by the senior author and on his own experience, the Denis classification for TL fractures was modified to develop a SCS-TL fractures that could guide the management. After Face and Content validation, Construct validation was done in two stages. First stage analyzed if management of 30 cases of TL fractures, as suggested by the SCS - TL fractures and ISCoS STSG (n = 9) as well as other (n = 5) experts, matched. Second stage was a one year prospective study analyzing if the management suggested matched the management actually carried out by different spine surgeons (n = 10) working at a single institution. RESULTS: In the first stage there was 100% agreement for management (conservative or surgical) as proposed by experts and that suggested by the proposed classification for TL fractures whereas for surgical approach there was 88% agreement. In the second stage, there was 100% agreement for the management as well as surgical approach as carried out at our centre and that proposed by the SCS for TL fractures. CONCLUSIONS: The proposed SCS-TL fractures helps in classifying and in decision making for management of TL fractures. The next phase of validation would involve multicentric reliability studies and prospective application of the SCS- TL fractures.

Comparison of outcomes between people with and without central cord syndrome.

STUDY DESIGN: Retrospective analysis of prospectively collected data. OBJECTIVE: Central cord syndrome (CCS) is reported to have better outcomes than other cervical lesions, especially for ambulation and bladder recovery. However, a formal comparison between patients with CCS and other incomplete cervical spinal cord injuries (iCSCI) is lacking. Aim of the study is to investigate the neurological and functional outcomes in patients with or without CCS. SETTING: European Multicenter Study. METHODS: Data following SCI were derived from the European Multicenter Study about Spinal Cord Injury Database. CCS was diagnosed based on a difference of at least ten points of motor score in favour of the lower extremities. Patients were evaluated at 30 days, 6 months and 1 year from injury. The neurological and functional data were collected at each time point based on the International Standards for Neurological Classification of Spinal Cord injury (ISNSCI) and Spinal Cord Independence Measure (SCIM). Patients were selected with a matching procedure based on lesion severity, neurological level of injury (NLI) and age. Evaluation of the outcomes was performed by means of two-way Anova for repeated measures. RESULTS: The matching produced 110 comparable dyads. At all time points, upper extremity motor scores remained lower than lower extremity motor scores in CCS compared with iCSCI. With regard to daily life independence, both cohorts achieved comparable improvements in self-care sub-scores between T0 and T2 (6.6 ± 6.5 in CCS vs 8.2 ± 6.9 in iCSCI, p = 0.15) but this sub-score was significantly lower in CCS compared with iCSCI (3.6 ± 5.2 in CCS vs 7.3 ± 7.0 in iCSCI at T0, 13.7 ± 6.2 vs 16.5 ± 5.7 at T2), while the other sub-scores were comparable. CONCLUSIONS: In contrast to previous reports, people with CCS have poorer outcomes of self-care ability compared with iCSCI.

Creation and validation of a new tool for the monitoring efficacy of neurogenic bowel dysfunction treatment on response: the MENTOR tool.

STUDY DESIGN: Prospective observational study. OBJECTIVES: A tool to help decision-making tool for Neurogenic Bowel Dysfunction (NBD) in individuals with SCI is needed. We present a project to create and validate a new tool, the Monitoring Efficacy of NBD Treatment On Response (MENTOR), and to determine its level of concordance with decisions made by experienced clinicians in the field. SETTING: UK, Denmark, USA, Italy, The Netherlands, Germany. METHODS: The first phase was creation of the tool through a modified Delphi process. The second phase was the validation, wherein individuals with spinal cord injury with NBD were asked to complete the MENTOR tool immediately prior to clinic consultation. From the responses to the questionnaire of the tool, each participant was allocated into one of three categories reflecting the possible therapeutic recommendations ("recommend change", "further discussion" and "monitoring"). An expert clinician then assessed the participant, blinded to MENTOR results, and made an independent treatment decision. RESULTS: A total of 248 MENTOR forms were completed. Strong agreement was found when the MENTOR tool recommended monitoring (92%) or treatment change (83%); the lowest concordance when the decision was for the "further discussion" option (59%). Patient acceptability was reported by 97% of individuals. CONCLUSIONS: MENTOR is an easy to use tool to monitor the treatment of NBD and determinate progression through the clinical pathway. This validation study shows good correspondence between expert clinician opinion and MENTOR result. The tool has potential to be used in other patient groups, following further studies.

Recovery after traumatic thoracic- and lumbar spinal cord injury: the neurological level of injury matters.

STUDY DESIGN: Multicenter prospective cohort. OBJECTIVE: To discern neurological- and functional recovery in patients with a traumatic thoracic spinal cord injury (TSCI), conus medullaris syndrome (CMS), and cauda equina syndrome (CES). SETTING: Specialized spinal cord injury centers in Europe. METHOD: Lower extremity motor score (LEMS) and spinal cord independent measure (SCIM) scores from patients with traumatic TSCI, CMS, and CES were extracted from the EMSCI database. Scores from admittance and during rehabilitation at 1, 3, 6, and 12 months were compared. Linear mixed models were used to statistically analyse differences in outcome, which were corrected for the ASIA Impairment Scale (AIS) in the acute phase. RESULTS: Data from 1573 individuals were analysed. Except for the LEMS in patients with a CES AIS A, LEMS, and SCIM significantly improved over time for patients with a TSCI, CMS, and CES. Irrespectively of the AIS score, recovery in 12 months after trauma as measured by the LEMS showed a statistically significant difference between patients with a TSCI, CMS, and CES. Analysis of SCIM score showed no difference between patients with TSCI, CMS, or CES. CONCLUSION: Difference in recovery between patients with a traumatic paraplegia is based on neurological (motor) recovery. Regardless the ceiling effect in CES patients, patients with a mixed upper and lower motor neuron syndrome (CMS) showed a better recovery compared with patients with a upper motor neuron syndrome (TSCI). These findings enable stratifications of patients with paraplegia according to the level and severity of SCI.

Management and prognosis of acute traumatic cervical central cord syndrome: systematic review and Spinal Cord Society-Spine Trauma Study Group position statement.

PURPOSE: Spinal Cord Society (SCS) and Spine Trauma Study Group (STSG) established a panel tasked with reviewing management and prognosis of acute traumatic cervical central cord syndrome (ATCCS) and recommend a consensus statement for its management. METHODS: A systematic review was performed according to the PRISMA 2009 guidelines. Delphi method was used to identify key research questions and achieve consensus. PubMed, Scopus and Google Scholar were searched for corresponding keywords. The initial search retrieved 770 articles of which 37 articles dealing with management, timing of surgery, complications or prognosis of ATCCS were identified. The literature review and draft position statements were compiled and circulated to panel members. The draft was modified incorporating relevant suggestions to reach consensus. RESULTS: Out of 37 studies, 15 were regarding management strategy, ten regarding timing of surgery and 12 regarding prognosis of ATCCS. CONCLUSION: There is reasonable evidence that patients with ATCCS secondary to vertebral fracture, dislocation, traumatic disc herniation or instability have better outcomes with early surgery (< 24 h). In patients of ATCCS secondary to extension injury in stenotic cervical canal without fracture/fracture dislocation/traumatic disc herniation/instability, there is requirement of high-quality prospective randomized controlled trials to resolve controversy regarding early surgery versus conservative management and delayed surgery if recovery plateaus or if there is a neurological deterioration. Until such time decision on surgery and its timing should be left to the judgment of physician, deliberating on pros and cons relevant to the particular patient and involving the well-informed patient and relatives in decision making. These slides can be retrieved under Electronic Supplementary Material.

Reliability of Allen Ferguson classification versus subaxial injury classification and severity scale for subaxial cervical spine injuries: a psychometrics study.

STUDY DESIGN: A psychometrics study. OBJECTIVES: To determine intra and inter-observer reliability of Allen Ferguson system (AF) and sub-axial injury classification and severity scale (SLIC), two sub axial cervical spine injury (SACI) classification systems. SETTING: Online multi-national study METHODS: Clinico-radiological data of 34 random patients with traumatic SACI were distributed as power point presentations to 13 spine surgeons of the Spine Trauma Study Group of ISCoS from seven different institutions. They were advised to classify patients using AF and SLIC systems. A reference guide of the two systems had been mailed to them earlier. After 6 weeks, the same cases were re-presented to them in a different order for classification using both systems. Intra and inter-observer reliability scores were calculated and analysed with Fleiss Kappa coefficient (k value) for both the systems and Intraclass correlation coefficient(ICC) for the SLIC. RESULTS: Allen Ferguson system displayed a uniformly moderate inter and intra-observer reliability. SLIC showed slight to fair inter-observer reliability and fair to substantial intra-observer reliability. AF mechanistic types showed better inter-observer reliability than the SLIC morphological types. Within SLIC, the total SLIC had the least inter-observer agreement and the SLIC neurology had the highest intra-observer agreement. CONCLUSION: This first external reliability study shows a better reliability for AF as compared to SLIC system. Among the SLIC variables, the DLC status and the total SLIC had least agreement. Low-reliability highlights the need for improving the existing classification systems or coming out with newer ones that consider limitations of the existing ones.

Reliability assessment of AOSpine thoracolumbar spine injury classification system and Thoracolumbar Injury Classification and Severity Score (TLICS) for thoracolumbar spine injuries: results of a multicentre study.

PURPOSE: The aim of this multicentre study was to determine whether the recently introduced AOSpine Classification and Injury Severity System has better interrater and intrarater reliability than the already existing Thoracolumbar Injury Classification and Severity Score (TLICS) for thoracolumbar spine injuries. METHODS: Clinical and radiological data of 50 consecutive patients admitted at a single centre with a diagnosis of an acute traumatic thoracolumbar spine injury were distributed to eleven attending spine surgeons from six different institutions in the form of PowerPoint presentation, who classified them according to both classifications. After time span of 6 weeks, cases were randomly rearranged and sent again to same surgeons for re-classification. Interobserver and intraobserver reliability for each component of TLICS and new AOSpine classification were evaluated using Fleiss Kappa coefficient (k value) and Spearman rank order correlation. RESULTS: Moderate interrater and intrarater reliability was seen for grading fracture type and integrity of posterior ligamentous complex (Fracture type: k = 0.43 ± 0.01 and 0.59 ± 0.16, respectively, PLC: k = 0.47 ± 0.01 and 0.55 ± 0.15, respectively), and fair to moderate reliability (k = 0.29 ± 0.01 interobserver and 0.44+/0.10 intraobserver, respectively) for total score according to TLICS. Moderate interrater (k = 0.59 ± 0.01) and substantial intrarater reliability (k = 0.68 ± 0.13) was seen for grading fracture type regardless of subtype according to AOSpine classification. Near perfect interrater and intrarater agreement was seen concerning neurological status for both the classification systems. CONCLUSIONS: Recently proposed AOSpine classification has better reliability for identifying fracture morphology than the existing TLICS. Additional studies are clearly necessary concerning the application of these classification systems across multiple physicians at different level of training and trauma centers to evaluate not only their reliability and reproducibility, but also the other attributes, especially the clinical significance of a good classification system.

Prediction of Bladder Outcomes after Traumatic Spinal Cord Injury: A Longitudinal Cohort Study.

BACKGROUND: Neurogenic bladder dysfunction represents one of the most common and devastating sequelae of traumatic spinal cord injury (SCI). As early prediction of bladder outcomes is essential to counsel patients and to plan neurourological management, we aimed to develop and validate a model to predict urinary continence and complete bladder emptying 1 y after traumatic SCI. METHODS AND FINDINGS: Using multivariate logistic regression analysis from the data of 1,250 patients with traumatic SCI included in the European Multicenter Spinal Cord Injury study, we developed two prediction models of urinary continence and complete bladder emptying 1 y after traumatic SCI and performed an external validation in 111 patients. As predictors, we evaluated age, gender, and all variables of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) and of the Spinal Cord Independence Measure (SCIM). Urinary continence and complete bladder emptying 1 y after SCI were assessed through item 6 of SCIM. The full model relies on lower extremity motor score (LEMS), light-touch sensation in the S3 dermatome of ISNCSI, and SCIM subscale respiration and sphincter management: the area under the receiver operating characteristics curve (aROC) was 0.936 (95% confidence interval [CI]: 0.922-0.951). The simplified model is based on LEMS only: the aROC was 0.912 (95% CI: 0.895-0.930). External validation of the full and simplified models confirmed the excellent predictive power: the aROCs were 0.965 (95% CI: 0.934-0.996) and 0.972 (95% CI 0.943-0.999), respectively. This study is limited by the substantial number of patients with a missing 1-y outcome and by differences between derivation and validation cohort. CONCLUSIONS: Our study provides two simple and reliable models to predict urinary continence and complete bladder emptying 1 y after traumatic SCI. Early prediction of bladder function might optimize counselling and patient-tailored rehabilitative interventions and improve patient stratification in future clinical trials.

Prediction of segmental motor outcomes in traumatic spinal cord injury: Advances beyond sum scores.

BACKGROUND AND OBJECTIVES: Neurological and functional recovery after traumatic spinal cord injury (SCI) is highly challenged by the level of the lesion and the high heterogeneity in severity (different degrees of in/complete SCI) and spinal cord syndromes (hemi-, ant-, central-, and posterior cord). So far outcome predictions in clinical trials are limited in targeting sum motor scores of the upper (UEMS) and lower limb (LEMS) while neglecting that the distribution of motor function is essential for functional outcomes. The development of data-driven prediction models of detailed segmental motor recovery for all spinal segments from the level of lesion towards the lowest motor segments will improve the design of rehabilitation programs and the sensitivity of clinical trials. METHODS: This study used acute-phase International Standards for Neurological Classification of SCI exams to forecast 6-month recovery of segmental motor scores as the primary evaluation endpoint. Secondary endpoints included severity grade improvement, independent walking, and self-care ability. Different similarity metrics were explored for k-nearest neighbor (kNN) matching within 1267 patients from the European Multicenter Study about Spinal Cord Injury before validation in 411 patients from the Sygen trial. The kNN performance was compared to linear and logistic regression models. RESULTS: We obtained a population-wide root-mean-squared error (RMSE) in motor score sequence of 0.76(0.14, 2.77) and competitive functional score predictions (AUCwalker = 0.92, AUCself-carer = 0.83) for the kNN algorithm, improving beyond the linear regression task (RMSElinear = 0.98(0.22, 2.57)). The validation cohort showed comparable results (RMSE = 0.75(0.13, 2.57), AUCwalker = 0.92). We deploy the final historic control model as a web tool for easy user interaction (https://hicsci.ethz.ch/). DISCUSSION: Our approach is the first to provide predictions across all motor segments independent of the level and severity of SCI. We provide a machine learning concept that is highly interpretable, i.e. the prediction formation process is transparent, that has been validated across European and American data sets, and provides reliable and validated algorithms to incorporate external control data to increase sensitivity and feasibility of multinational clinical trials.

How Do Everyday Life Activities Affect Seating Pressure Measurements?

BACKGROUND: Pressure measurements to detect risks for pressure injuries in wheelchair users with spinal cord injury (SCI) have been available for quite some time. Unfortunately, knowledge of how postural changes during longer periods of daily life activity affecting the results is still limited. In the present study, the authors expected to note shifts in the center of pressure as well as in the pressure distribution, especially in patients who were able to change their position actively. METHODS: A seat pressure mat (BodiTrak2) was used to perform measurements of 34 SCI wheelchair users after initial transfer into the wheelchair as well as 30 and 90 minutes later. Mean pressure, maximum pressure, pressure-loaded measuring surface, and the coordinates of the center of pressure were analyzed, and findings were statistically analyzed using the t test and Intraclass Correlation Coefficient. To quantify the drift of the measurement system, recordings with a reference weight were performed. RESULTS: The analyzed parameters from the initial measurement differed significantly from the later measurements at 30 and 90 minutes, whereas the parameters were stable after 30 minutes. The measurements with the reference weight showed the same measurement course. CONCLUSIONS: The measurements after 30 and 90 minutes were consistent, contrary to expectations. The activity of the participant between measurements did not appear to be of much importance. CLINICAL RELEVANCE: Relief maneuvers appear to provide relief only while the maneuver is being performed. Thus, relief activities must be frequent enough and long enough to allow adequate blood flow to the tissues.

Segmental motor recovery after cervical spinal cord injury relates to density and integrity of corticospinal tract projections.

Cervical spinal cord injury (SCI) causes extensive impairments for individuals which may include dextrous hand function. Although prior work has focused on the recovery at the person-level, the factors determining the recovery of individual muscles are poorly understood. Here, we investigate the muscle-specific recovery after cervical spinal cord injury in a retrospective analysis of 748 individuals from the European Multicenter Study about Spinal Cord Injury (NCT01571531). We show associations between corticospinal tract (CST) sparing and upper extremity recovery in SCI, which improves the prediction of hand muscle strength recovery. Our findings suggest that assessment strategies for muscle-specific motor recovery in acute spinal cord injury are improved by accounting for CST sparing, and complement person-level predictions.

Walking Outcome After Traumatic Paraplegic Spinal Cord Injury: The Function of Which Myotomes Makes a Difference?

BACKGROUND: Accurate prediction of walking function after a traumatic spinal cord injury (SCI) is crucial for an appropriate tailoring and application of therapeutical interventions. Long-term outcome of ambulation is strongly related to residual muscle function acutely after injury and its recovery potential. The identification of the underlying determinants of ambulation, however, remains a challenging task in SCI, a neurological disorder presented with heterogeneous clinical manifestations and recovery trajectories. OBJECTIVES: Stratification of walking function and determination of its most relevant underlying muscle functions based on stratified homogeneous patient subgroups. METHODS: Data from individuals with paraplegic SCI were used to develop a prediction-based stratification model, applying unbiased recursive partitioning conditional inference tree (URP-CTREE). The primary outcome was the 6-minute walk test at 6 months after injury. Standardized neurological assessments ≤15 days after injury were chosen as predictors. Resulting subgroups were incorporated into a subsequent node-specific analysis to attribute the role of individual lower extremity myotomes for the prognosis of walking function. RESULTS: Using URP-CTREE, the study group of 361 SCI patients was divided into 8 homogeneous subgroups. The node specific analysis uncovered that proximal myotomes L2 and L3 were driving factors for the differentiation between walkers and non-walkers. Distal myotomes L4-S1 were revealed to be responsible for the prognostic distinction of indoor and outdoor walkers (with and without aids). CONCLUSION: Stratification of a heterogeneous population with paraplegic SCI into more homogeneous subgroups, combined with the identification of underlying muscle functions prospectively determining the walking outcome, enable potential benefit for application in clinical trials and practice.

Inclusive Trial Designs in Acute Spinal Cord Injuries: Prediction-Based Stratification of Clinical Walking Outcome and Projected Enrolment Frequencies.

BACKGROUND: New therapeutic approaches in neurological disorders are progressing into clinical development. Past failures in translational research have underlined the critical importance of selecting appropriate inclusion criteria and primary outcomes. Narrow inclusion criteria provide sensitivity, but increase trial duration and cost to the point of infeasibility, while broader requirements amplify confounding, increasing the risk of trial failure. This dilemma is perhaps most pronounced in spinal cord injury (SCI), but applies to all neurological disorders with low frequency and/or heterogeneous clinical manifestations. OBJECTIVE: Stratification of homogeneous patient cohorts to enable the design of clinical trials with broad inclusion criteria. METHODS: Prospectively-gathered data from patients with acute cervical SCI were analysed using an unbiased recursive partitioning conditional inference tree (URP-CTREE) approach. Performance in the 6-minute walk test at 6 months after injury was classified based on standardized neurological assessments within the first 15 days of injury. Functional and neurological outcomes were tracked throughout rehabilitation up to 6 months after injury. RESULTS: URP-CTREE identified homogeneous outcome cohorts in a study group of 309 SCI patients. These cohorts were validated by an internal, yet independent, validation group of 172 patients. The study group cohorts identified demonstrated distinct recovery profiles throughout rehabilitation. The baseline characteristics of the analysed groups were compared to a reference group of 477 patients. CONCLUSION: URP-CTREE enables inclusive trial design by revealing the distribution of outcome cohorts, discerning distinct recovery profiles and projecting potential patient enrolment by providing estimates of the relative frequencies of cohorts to improve the design of clinical trials in SCI and beyond.