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 DESIGN: Consensus process. OBJECTIVES: To 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. SETTING: Committee with 16 ISNCSCI experts and datasets from the European Multicenter Study about Spinal Cord Injury (EMSCI). METHODS: Occurrence frequencies of applicable ZPPs were determined in an EMSCI cohort consisting of two ISNCSCI examinations from 665 individuals with traumatic SCI. RESULTS: Motor 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). CONCLUSIONS: The 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. SPONSORSHIP: N/A.

Lower Motoneuron Dysfunction Impacts Spontaneous Motor Recovery in Acute Cervical Spinal Cord Injury.

Paresis after spinal cord injury (SCI) is caused by damage to upper and lower motoneurons (LMNs) and may differentially impact neurological recovery. This prospective monocentric longitudinal observational study investigated the extent and severity of LMN dysfunction and its impact on upper extremity motor recovery after acute cervical SCI. Pathological spontaneous activity at rest and/or increased discharge rates of motor unit action potentials recorded by needle electromyography (EMG) were taken as parameters for LMN dysfunction and its relation to the extent of myelopathy in the first available spine magnetic resonance imaging (MRI) was determined. Motor recovery was assessed by standardized neurological examination within the first four weeks (acute stage) and up to one year (chronic stage) after injury. Eighty-five muscles of 17 individuals with cervical SCI (neurological level of injury from C1 to C7) and a median age of 54 (28-59) years were examined. The results showed that muscles with signs of LMN dysfunction peaked at the lesion center (Χ2 [2, n = 85] = 6.6, p = 0.04) and that the severity of LMN dysfunction correlated with T2-weighted hyperintense MRI signal changes in routine spine MRI at the lesion site (Spearman ρ = 0.31, p = 0.01). Muscles exhibiting signs of LMN dysfunction, as indicated by pathological spontaneous activity at rest and/or increased discharge rates of motor unit action potentials, were associated with more severe paresis in both the acute and chronic stages after SCI (Spearman ρ acute = -0.22, p = 0.04 and chronic = -0.31, p = 0.004). Moreover, the severity of LMN dysfunction in the acute stage was also associated with a greater degree of paresis (Spearman ρ acute = -0.24, p = 0.03 and chronic = -0.35, p = 0.001). While both muscles with and without signs of LMN dysfunction were capable of regaining strength over time, those without LMN dysfunctions had a higher potential to reach full strength. Muscles with signs of LMN dysfunction in the acute stage displayed increased amplitudes of motor unit action potentials with chronic-stage needle EMG, indicating reinnervation through peripheral collateral sprouting as compensatory mechanism (Χ2 [1, n = 72] = 4.3, p = 0.04). Thus, LMN dysfunction represents a relevant factor contributing to motor impairment and recovery in acute cervical SCI. Defined recovery mechanisms (peripheral reinnervation) may at least partially underlie spontaneous recovery in respective muscles. Therefore, assessment of LMN dysfunction could help refine prediction of motor recovery after SCI.

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

STUDY DESIGN: Literature review and survey. OBJECTIVES: To 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. SETTING: Not applicable. METHODS: Literature review according to three organizing concepts for evaluation of Health Information Products (reach, usefulness, and use) was conducted. RESULTS: While 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. CONCLUSIONS: Validated 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.

Metadata Definition in Registries: What Is a Data Element?

Observational research benefits from a rich methodological foundation of registry development and operation published in international and national guidelines. Metadata management is an essential part of registry implementation based on concepts of data elements and value sets. The metadata from six German registries revealed vastly divergent interpretations of the concept of data elements. The different perspectives of research questions, data acquisition and data storage were all represented in the registries' catalogs of data elements. Consequently, the whole life cycle of a registry needs to be accompanied by a catalog of data elements, which has to be continuously adapted to the changing perspectives. A standard for the representation of those metadata is still missing. The FAIR Guiding Principles introduce important methodological requirements, but the tools for their fulfillment in respect to the management of metadata are still in its infancy.

Impact of Heterotopic Ossification on Functional Recovery in Acute Spinal Cord Injury.

Objective: In spinal cord injury (SCI), heterotopic ossification is a frequent secondary complication, commonly associated with limited range of motion of affected joints, which could lead to secondary disability in activities of daily living. Additionally, heterotopic ossifications might challenge the effect of regeneration-promoting therapies on neurological and functional recovery. This study evaluated the impact of heterotopic ossification on clinical recovery within the first year after SCI. Methods: The study was conducted as a monocentric longitudinal paired cohort study. Recruitment was based on consecutive sampling in the framework of the European Multicenter about Spinal Cord Injury (EMSCI). Recovery profiles were determined using standardized neurological and functional clinical assessments within the 1st year following SCI. All study participants underwent at least two comprehensive standardized neurological and functional clinical examinations according to the International Standards for Neurological Classification of SCI and the Spinal Cord Independence Measure, respectively. Data regarding the diagnosis and treatment of heterotopic ossification were obtained by reviewing the patient medical records. The most similar "digital twin" from the entire EMSCI database were matched in terms of age, acute neurological and functional status to each individual with SCI, and heterotopic ossification. Results: Out of 25 participants diagnosed with heterotopic ossification, 13 individuals were enrolled and matched to control individuals. Most individuals presented with motor complete injury (75%). Ossifications were most frequently located at the hip joints (92%) and mainly occurred within the first 3 months after SCI. Individuals with heterotopic ossification achieved around 40% less functional improvement over time compared to their matched counterparts, whereas neurological recovery was not altered in individuals with SCI and heterotopic ossification. Conclusion: Heterotopic ossification-a common complication of SCI-unfavorably affects functional recovery, which in the end is most relevant for the best possible degree of independence in activities of daily living. Upon presentation with heterotopic ossification, neurological improvement achieved through potential restorative therapies might not translate into clinically meaningful functional improvement. Diagnostic algorithms and effective early prevention/treatment options for heterotopic ossification need to be established to ensure the best possible functional outcome. Clinical Trial Registration: NCT01571531 (https://clinicaltrials.gov).

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

OBJECTIVES: Since 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). METHODS: The 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. RESULTS: The 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. CONCLUSIONS: The possibility of multilingual implementations independent from software developers opens the use of ISNCSCI computer algorithms as an efficient training tool on a larger scale.

A taxonomy for consistent handling of conditions not related to the spinal cord injury (SCI) in the International Standards for Neurological Classification of SCI (ISNCSCI).

STUDY DESIGN: Committee consensus process including additional structured feedback from spinal cord injury (SCI) experts attending a focus group workshop. OBJECTIVES: To define a taxonomy for standardized documentation of non-SCI-related conditions in the International Standards for Neurological Classification of SCI (ISNCSCI). SETTING: Americal Spinal Injury Association (ASIA) International Standards Committee with 16 international ISNCSCI experts. METHODS: With the new taxonomy, not-normal sensory or motor scores should be tagged with an asterisk ("*"), if they are impacted by a non-SCI condition such as burns, casts, joint contractures, peripheral nerve injuries, amputations, pain, or generalized weakness. The non-SCI condition and instructions on how to handle the "*"-tagged scores during classification should be detailed in the comments box. While sum scores are always calculated based on examined scores, classification variables such as the neurological level of injury (NLI) or the ASIA Impairment Scale (AIS) grades are tagged with an "*", when they have been determined on the basis of clinical assumptions. RESULTS: With the extended "*"-tag concept, sensory and motor examination results impacted by non-SCI conditions above, at, or below the NLI can be consistently documented, scored, and classified. Feedback from workshop participants confirms agreement on its clinical relevance, logic and soundness, easiness of understanding, communicability, and applicability in daily work. CONCLUSIONS: After multiple internal revisions, a taxonomy for structured documentation of conditions superimposed on the impairments caused by the SCI together with guidelines for consistent scoring and classification was released with the 2019 ISNCSCI revision. This taxonomy is intended to increase the accuracy of ISNCSCI classifications.

Theoretical and practical training improves knowledge of the examination guidelines of the International Standards for Neurological Classification of Spinal Cord Injury.

STUDY DESIGN: Prospective pre-post study. OBJECTIVES: International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) represents the most frequently used assessment to determine the level and severity of a spinal cord injury (SCI). The guidelines for ISNCSCI are complex and challenging. Knowledge of its correct execution needs to be imparted precisely. The aim of this study was to investigate whether hands-on instructional courses can increase the knowledge of the ISNCSCI examination guidelines. SETTING: European Multicenter Study about SCI. METHODS: Before and after the instructional courses, participants were asked to complete questionnaires. The set of questions covered the most important aspects of the examination guidelines. Attendees were asked to self-rate their occupation and experience in ISNCSCI. RESULTS: The comparison of pretest and posttest results of 164 attendees from 2014 to 2018 revealed an improvement of knowledge reflected by an increase of correct answers from 66 ± 17% before to 89 ± 11% after the course (p < 0.01). The improvement was not associated with occupation (p > 0.1). However, the correctness of pretest results differed concerning both the period of experience with ISNCSCI (p < 0.05) and the course language (p < 0.01), while the frequency of execution resulted in differences in the posttest (p = 0.01). CONCLUSIONS: Instructional courses substantially improve knowledge of the ISNCSCI examination guidelines. Differences in knowledge present before the course leveled off after the course. Comprehensive theoretical training is strongly recommended to ensure reliability and validity of ISNCSCI examinations in clinical routine and research. Albeit being practiced in the instructional courses, the benefit of hands-on training still needs to be systematically evaluated in future studies.

[Germany-wide, Web-based ParaReg Registry for Lifelong Monitoring of People with Spinal Cord Injury: Data Model, Ethico-legal Prerequisites and Technical Implementation]. / Das deutschlandweite, webbasierte ParaReg-Register zur lebenslangen Dokumentation von Querschnittgelähmten ­ Datenmodell, rechtlich-ethische Voraussetzungen und technische Implementierung.

OBJECTIVE: In Germany, treatment paths for patients with acute spinal cord injury (SCI) differ considerably depending on intrinsic, disease-specific and extrinsic factors. Which of these factors are associated with improved outcome with fewer subsequent complications and inpatient re-admissions is not clear. The German-wide, patient-centered, web-based ParaReg registry will be implemented to improve the long-term quality of patient care and the planning of treatment paths with increased cost-effectiveness. METHODS: In the 2017-18 conceptualization phase, the data model of the registry was developed in an iterative process of the ParaReg steering committee together with the extended DMGP board and patient representatives. In ParaReg, routine social and medical data as well as internationally established neurological, functional and participation scores will be documented. The assignment of a unique patient ID allows a lifelong, cross-center documentation of inpatient stays in one of the 27 SCI centers organized in the German-speaking Medical Society for SCI (DMGP). The ParaReg data protection concept and patient information/consent are based on the Open Source Registry for Rare Diseases (OSSE) which were extended by GDPR-relevant aspects. RESULTS: In the realization phase, which started in 2019, the information technology infrastructure was implemented according to the clinical ID management module of the Technology and Methods Platform for Networked Medical Research (TMF). In parallel, the legal and ethical prerequisites for registry operation under the patronage of the DMGP were created. Recommendations of the working group data protection of the TMF were integrated into ParaReg's data protection concept. Based on the feedback from the alpha test phase with documentation of the hospitalization data of 40 patients, the ergonomics of the electronic case report forms were improved in particular for data entry on mobile devices. CONCLUSION: After completion of the monocentric alpha test phase, the multicenter data acquisition was started in 5 DMGP-SCI centers. The sustainability of ParaReg is ensured by the structural and financial support of the DMGP after expiry of the funding by the German Federal Ministry of Education and Research (BMBF).

Revisiting the Examination of Sharp/Dull Discrimination as Clinical Measure of Spinothalamic Tract Integrity.

Objective: Revisiting the sharp/dull discrimination as clinical measure of spinothalamic tract function considering the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). Three clinically relevant factors were evaluated as to their impact on reliability: (1) the localization of dermatomes in relation to the sensory level, (2) the examination tool, and (3) the threshold of correct answers for grading of a preserved sharp/dull discrimination. Design: Prospective monocentric psychometric study. Setting: Spinal Cord Injury Center, Heidelberg University Hospital, Germany. Participants: Convenient sample of 21 individuals with subacute spinal cord injury (age: 31-82 years) and 20 individuals without spinal cord injury (age: 24-63 years). Assessment: All participants underwent three assessments for sharp/dull discrimination, applying five commonly used examination tools in seven dermatomes, performed by three trained examiners under conditions in accordance with ISNCSCI. Main Outcome Measures: Assessment of interrater reliability by determining both the Fleiss kappa (κ) coefficient and the percentage agreement between raters. Data were dichotomized regarding the ISNCSCI threshold. Results: Interrater reliability in individuals with SCI was overall substantial (κ = 0.68; CI 0.679-0.681) and moderate (κ = 0.54; CI 0.539-0.543) in dermatomes below the sensory level. All applied tools led to at least moderate reliability below the sensory level (lowest κ = 0.44; CI 0.432-0.440), with the officially endorsed safety pin achieving the highest (substantial) reliability (κ = 0.64; CI 0.638-0.646). Percentage agreement differed between non-SCI (97.3%) and formally intact above level dermatomes in SCI (89.2%). Conclusions: Sharp/dull discrimination as a common clinical examination technique for spinothalamic tract function is a reliable assessment. Independent from the used examination tools, reliability was substantial, with the medium-sized safety pin delivering the most favorable results. Notwithstanding this, all other tools could be considered if a safety pin is not available. Regarding interrater reliability and guessing probability, a threshold of 80% correct responses for preserved sharp/dull discrimination appears to be most suitable, which is in line with current clinical approaches and ISNCSCI. The causal attribution of the identified differences in sharp/dull discrimination between clinically intact dermatomes of individuals with SCI and unaffected dermatomes of individuals without SCI requires future work. Clinical Trial Registration Number (German Clinical Trials Register): DRKS00015334 (https://www.drks.de).

Influence of patient isolation due to colonization with multidrug-resistant organisms on functional recovery after spinal cord injury.

STUDY DESIGN: Chart reviews were combined with neurological and functional outcome data obtained from the prospective European Multicenter Study on Spinal Cord Injury (EMSCI, www.emsci.org). OBJECTIVES: To determine if strict physical isolation of multidrug-resistant organisms (MDRO)-positive patients negatively affects neurological recovery and functional outcome in the first year after acute spinal cord injury (SCI). SETTING: SCI Center Heidelberg University Hospital. METHODS: Individuals with acute (< 6 weeks) traumatic or ischemic SCI were included. During primary comprehensive care, isolated MDRO-positive patients (n = 13) were compared with a MDRO-negative control group (n = 13) matched for functional (Spinal Cord Independence Measure-SCIM) and neurological impairment (motor scores based on the International Standards for Neurological Classification of Spinal Cord Injury-ISNCSCI) at an early stage up to 40 days after SCI. SCIM scores and motor scores were obtained at 12 weeks (intermediate stage) and 24 or 48 weeks (late stage) after SCI. RESULTS: Isolated MDRO-positive (median duration of hospitalization: 175 days, 39% of inpatient stay under isolation measures) and non-isolated MDRO-negative (median duration of hospitalization: 161 days) patients showed functional and neurological improvements, which were not statistically different between groups at the intermediate and late stage. CONCLUSION: Prolonged isolation due to MDRO colonization for over a third of the inpatient comprehensive care period does not appear to impair neurological recovery and functional outcome within the first year after SCI.

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

BACKGROUND: Accurate predictors of neurological recovery after cervical spinal cord injury are needed. Particularly, to tailor adequate rehabilitation plans. However, objective and quantifiable predictors are sparse. METHODS: Within 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. RESULTS: In 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). CONCLUSIONS: In 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.

Trainer in a pocket - proof-of-concept of mobile, real-time, foot kinematics feedback for gait pattern normalization in individuals after stroke, incomplete spinal cord injury and elderly patients.

BACKGROUND: Walking disabilities negatively affect inclusion in society and quality of life and increase the risk for secondary complications. It has been shown that external feedback applied by therapists and/or robotic training devices enables individuals with gait abnormalities to consciously normalize their gait pattern. However, little is known about the effects of a technically-assisted over ground feedback therapy. The aim of this study was to assess whether automatic real-time feedback provided by a shoe-mounted inertial-sensor-based gait therapy system is feasible in individuals with gait impairments after incomplete spinal cord injury (iSCI), stroke and in the elderly. METHODS: In a non-controlled proof-of-concept study, feedback by tablet computer-generated verbalized instructions was given to individuals with iSCI, stroke and old age for normalization of an individually selected gait parameter (stride length, stance or swing duration, or foot-to-ground angle). The training phase consisted of 3 consecutive visits. Four weeks post training a follow-up visit was performed. Visits started with an initial gait analysis (iGA) without feedback, followed by 5 feedback training sessions of 2-3 min and a gait analysis at the end. A universal evaluation and FB scheme based on equidistant levels of deviations from the mean normal value (1 level = 1 standard deviation (SD) of the physiological reference for the feedback parameter) was used for assessment of gait quality as well as for automated adaptation of training difficulty. Overall changes in level over iGAs were detected using a Friedman's Test. Post-hoc testing was achieved with paired Wilcoxon Tests. The users' satisfaction was assessed by a customized questionnaire. RESULTS: Fifteen individuals with iSCI, 11 after stroke and 15 elderly completed the training. The average level at iGA significantly decreased over the visits in all groups (Friedman's test, p < 0.0001), with the biggest decrease between the first and second training visit (4.78 ± 2.84 to 3.02 ± 2.43, p < 0.0001, paired Wilcoxon test). Overall, users rated the system's usability and its therapeutic effect as positive. CONCLUSIONS: Mobile, real-time, verbalized feedback is feasible and results in a normalization of the feedback gait parameter. The results form a first basis for using real-time feedback in task-specific motor rehabilitation programs. TRIAL REGISTRATION: DRKS00011853 , retrospectively registered on 2017/03/23.

Differences in Characteristics of Error-Related Potentials Between Individuals With Spinal Cord Injury and Age- and Sex-Matched Able-Bodied Controls.

Background: Non-invasive brain-computer interfaces (BCI) represent an emerging technology for enabling persons with impaired or lost grasping and reaching functions due to high spinal cord injury (SCI) to control assistive devices. A major drawback of BCIs is a high rate of false classifications. The robustness and performance of BCIs might be improved using cerebral electrophysiological correlates of error recognition (error-related potentials, ErrPs). As ErrPs have never been systematically examined in subjects with SCI, this study compares the characteristics of ErrPs in individuals with SCI with those of able-bodied control subjects. Methods: ErrPs at FCz and Cz were analyzed in 11 subjects with SCI (9 male, median age 28 y) and in 11 sex- and age-matched controls. Moving a shoulder joystick according to a visual cue, subjects received feedback about the match/mismatch of the performed movement. ErrPs occurring after "error"-feedback were evaluated by comparing means of voltage values within three consecutive time windows after feedback (wP1, wN1, wP2 containing peak voltages P1, N1, P2) using repeated-measurement analysis of variance. Results: In the control group, mean voltage values for the "error" and "correct" feedback condition differed significantly around N1 (FCz: 254 ms, Cz: 252 ms) and P2 (FCz: 347 ms, Cz: 345 ms), but not around P1 (FCz: 181 ms, Cz: 179 ms). ErrPs of the control and the SCI group showed similar morphology, however mean amplitudes of ErrPs were significantly smaller in individuals with SCI compared to controls for wN1 (FCz: control = -1.55 µV, SCI = -0.27 µV, p = 0.02; Cz: control = -1.03 µV, SCI = 0.11 µV, p = 0.04) and wP2 (FCz: control = 2.79 µV, SCI = 1.29 µV, p = 0.011; Cz: control = 2.12 µV, SCI = 0.81 µV, p = 0.003). Mean voltage values in wP1, wN1, and wP2 did not correlate significantly with either chronicity after or level of injury. Conclusion: The morphology of ErrPs in subjects with and without SCI is comparable, however, with reduced mean amplitude in wN1 and wP2 in the SCI group. Further studies should evaluate whether ErrP-classification can be used for online correction of false BCI-commands in individuals with SCI.

Sensory Feedback Interferes with Mu Rhythm Based Detection of Motor Commands from Electroencephalographic Signals.

Background: Electroencephalogram (EEG)-based brain-computer interfaces (BCI) represent a promising component of restorative motor therapies in individuals with partial paralysis. However, in those patients, sensory functions such as proprioception are at least partly preserved. The aim of this study was to investigate whether afferent feedback interferes with the BCI-based detection of efferent motor commands during execution of movements. Methods: Brain activity of 13 able-bodied subjects (age: 29.1 ± 4.8 years; 11 males) was compared between a motor task (MT) consisting of an isometric, isotonic grip and a somatosensory electrical stimulation (SS) of the fingertips. Modulation of the mu rhythm (8-13 Hz) was investigated to identify changes specifically related to the generation of efferent commands. A linear discriminant analysis (LDA) was used to investigate the activation pattern on a single-trial basis. Classifiers were trained with MT vs. REST (periods without MT/SS) and tested with SS and vice versa to quantify the impact of afferent feedback on the classification results. Results: Few differences in the spatial pattern between MT and SS were found in the modulation of the mu rhythm. All were characterized by event-related desynchronization (ERD) peaks at electrodes C3, C4, and CP3. Execution of the MT was associated with a significantly stronger ERD in the majority of sensorimotor electrodes [C3 (p < 0.01); CP3 (p < 0.05); C4 (p < 0.01)]. Classification accuracy of MT vs. REST was significantly higher than SS vs. REST (77% and 63%; p < 10-8). Classifiers trained on MT vs. REST were able to classify SS trials significantly above chance even though no motor commands were present during SS. Classifiers trained on SS performed better in classifying MT instead of SS. Conclusion: Our results challenge the notion that the modulation of the mu rhythm is a robust phenomenon for detecting efferent commands when afferent feedback is present. Instead, they indicate that the mu ERD caused by the processing of afferent feedback generates ERD patterns in the sensorimotor cortex that are masking the ERD patterns caused by the generation of efferent commands. Thus, processing of afferent feedback represents a considerable source of false positives when the mu rhythm is used for the detection of efferent commands.

Early Administration of Gabapentinoids Improves Motor Recovery after Human Spinal Cord Injury.

The anticonvulsant pregabalin promotes neural regeneration in a mouse model of spinal cord injury (SCI). We have also previously observed that anticonvulsants improve motor outcomes following human SCI. The present study examined the optimal timing and type of anticonvulsants administered in a large, prospective, multi-center, cohort study in acute SCI. Mixed-effects regression techniques were used to model total motor scores at 1, 3, 6, and 12 months post injury. We found that early (not late) administration of anticonvulsants significantly improved motor recovery (6.25 points over 1 year). The beneficial effect of anticonvulsants remained significant after adjustment for differences in 1-month motor scores and injury characteristics. A review of a subset of patients revealed that gabapentinoids were the most frequently administrated anticonvulsant. Together with preclinical findings, intervention with anticonvulsants represents a potential pharmacological strategy to improve motor function after SCI.

International standards for neurological classification of spinal cord injury: impact of the revised worksheet (revision 02/13) on classification performance.

STUDY DESIGN: Prospective cohort study. OBJECTIVES: Comparison of the classification performance between the worksheet revisions of 2011 and 2013 of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). SETTINGS: Ongoing ISNCSCI instructional courses of the European Multicenter Study on Human Spinal Cord Injury (EMSCI). For quality control all participants were requested to classify five ISNCSCI cases directly before (pre-test) and after (post-test) the workshop. PARTICIPANTS: One hundred twenty-five clinicians working in 22 SCI centers attended the instructional course between November 2011 and March 2015. Seventy-two clinicians completed the post-test with the 2011 revision of the worksheet and 53 with the 2013 revision. INTERVENTIONS: Not applicable. OUTCOME MEASURES: The clinicians' classification performance assessed by the percentage of correctly determined motor levels (ML) and sensory levels, neurological levels of injury (NLI), ASIA Impairment Scales and zones of partial preservations. RESULTS: While no group differences were found in the pre-tests, the overall performance (rev2011: 92.2% ± 6.7%, rev2013: 94.3% ± 7.7%; P = 0.010), the percentage of correct MLs (83.2% ± 14.5% vs. 88.1% ± 15.3%; P = 0.046) and NLIs (86.1% ± 16.7% vs. 90.9% ± 18.6%; P = 0.043) improved significantly in the post-tests. Detailed ML analysis revealed the largest benefit of the 2013 revision (50.0% vs. 67.0%) in a case with a high cervical injury (NLI C2). CONCLUSION: The results from the EMSCI ISNCSCI post-tests show a significantly better classification performance using the revised 2013 worksheet presumably due to the body-side based grouping of myotomes and dermatomes and their correct horizontal alignment. Even with these proven advantages of the new layout, the correct determination of MLs in the segments C2-C4 remains difficult.

Motor levels in high cervical spinal cord injuries: Implications for the International Standards for Neurological Classification of Spinal Cord Injury.

CONTEXT/OBJECTIVE: To verify the hypothesis that motor levels (ML) inferred from sensory levels in the upper cervical segments C2-C4 according to the current version of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) are counterintuitive in cases where the most rostral myotomes C5 and C6 are graded as intact. DESIGN: Prospective cohort study of ISNCSCI instructional course participants completing a post-test after the workshop to determine the MLs in two variants of a complete, high cervical spinal cord injury (SCI) case scenario. Both variants were based on the same ISNCSCI sensory and MLs of C2. In the first variant myotomes C5 and C6 were bilaterally graded as intact, while in variant 2 only active movements against gravity were possible (grade 3). SETTING: Eight ISNCSCI instructional courses conducted during the study period from November 2012 until March 2015 in the framework of the European Multicenter Study on Human Spinal Cord Injury (EMSCI- http//emsci.org ). PARTICIPANTS: Ninety-two clinicians from twenty-two SCI centers. Most of the attendees were physicians (58.7%) or physical therapists (33.7%) and had less than one year (44.6%) experience in SCI medicine. INTERVENTIONS: Not applicable. OUTCOME MEASURE: The classification performance described as percentage of correctly determined MLs by the clinicians. RESULTS: Variant 2 (89.13%) was significantly (P < 0.0001) better classified than variant 1 (65.76%). In variant 1 with intact myotomes at C5 and C6, C6 was incorrectly classified as the ML by the clinicians in 33.15% of all cases, whereas in variant 2 with non-intact C5 / C6 myotomes, C6 was rarely chosen (2.17%). CONCLUSIONS: Sensory level deferred MLs in the high cervical region of C2-C4 are counterintuitive whenever the most rostral cervical myotomes are intact. An adjustment of the ML definition in ISNCSCI may be needed.

Effects of Pain and Pain Management on Motor Recovery of Spinal Cord-Injured Patients: A Longitudinal Study.

Background Approximately 60% of patients suffering from acute spinal cord injury (SCI) develop pain within days to weeks after injury, which ultimately persists into chronic stages. To date, the consequences of pain after SCI have been largely examined in terms of interfering with quality of life. Objective The objective of this study was to examine the effects of pain and pain management on neurological recovery after SCI. Methods We analyzed clinical data in a prospective multicenter observational cohort study in patients with SCI. Using mixed effects regression techniques, total motor and sensory scores were modelled at 1, 3, 6, and 12 months postinjury. Results A total of 225 individuals were included in the study (mean age: 45.8 ± 18 years, 80% male). At 1 month postinjury, 28% of individuals with SCI reported at- or below-level neuropathic pain. While pain classification showed no effect on neurological outcomes, individuals administered anticonvulsant medications at 1 month postinjury showed significant reductions in pain intensity (2 points over 1 year; P < .05) and greater recovery in total motor scores (7.3 points over 1 year; P < .05). This drug effect on motor recovery remained significant after adjustment for injury level and injury severity, pain classification, and pain intensity. Conclusion While initial pain classification and intensity did not reveal an effect on motor recovery following acute SCI, anticonvulsants conferred a significant beneficial effect on motor outcomes. Early intervention with anticonvulsants may have effects beyond pain management and warrant further studies to evaluate the therapeutic effectiveness in human SCI.