Comparing surgeries to restore upper extremity function in tetraplegia: Impact on function during the perioperative period.

Context/objective: To assess short-term changes in health outcomes in people with cervical-level spinal cord injury (SCI) who underwent upper extremity (UE) reconstruction via either novel nerve transfer (NT) or traditional tendon transfer (TT) surgery with individuals who did not undergo UE surgical reconstruction.

Design: Prospective, comparative cohort pilot study.

Participants: 34 participants with cervical SCI met the following inclusion criteria: age 18 or older, greater than 6 months post-injury, and mid-cervical level SCI American Spinal Injury Association Impairment Scale (AIS) A, B or C.

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.

Spontaneous Motor Recovery after Cervical Spinal Cord Injury: Issues for Nerve Transfer Surgery Decision Making.

Study Design: Retrospective cohort study.

Objectives: To quantify spontaneous upper extremity motor recovery between 6 and 12 months after spinal cord injury (SCI) to help guide timing of nerve transfer surgery to improve upper limb function in cervical SCI.

Setting: Nineteen European SCI rehabilitation centers.

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.

Evaluation of Functional Independence in Cervical Spinal Cord Injury: Implications for Surgery to Restore Upper Limb Function.

Purpose: To help individuals make informed choices regarding the optimal type and timing of restorative surgical treatment for cervical spinal cord injury (SCI), more precise information is needed on their ability to perform activities of daily living. The goal of this work was to describe functional independence achieved by individuals with differing levels of cervical SCI.

Methods: Using the comprehensive European Multicenter Study of Spinal Cord Injury dataset, analysis was undertaken of individuals with traumatic SCI, motor-level C5-C8.

Adaptive trial designs for spinal cord injury clinical trials directed to the central nervous system.

Study Design: Narrative review.

Purpose: To provide an overview of adaptive trial designs, and describe how adaptive methods can address persistent challenges encountered by randomized controlled trials of people with spinal cord injury (SCI).

Results: With few exceptions, adaptive methodologies have not been incorporated into clinical trial designs of people with SCI.

The challenge of recruitment for neurotherapeutic clinical trials in spinal cord injury.

Study Design: Narrative review by individuals experienced in the recruitment of participants to neurotherapeutic clinical trials in spinal cord injury (SCI).

Objectives: To identify key problems of recruitment and explore potential approaches to overcoming them.

Methods: Published quantitative experience with recruitment of large-scale, experimental neurotherapeutic clinical studies targeting central nervous system and using primary outcome assessments validated for SCI over the last 3 decades was summarized.

Correction: Evidence-based scientific exercise guidelines for adults with spinal cord injury: an update and a new guideline.

Authors Victoria L. Goosey-Tolfrey and Karen M. Smith were listed under the incorrect affiliations at the time of publication.

Considerations and recommendations for selection and utilization of upper extremity clinical outcome assessments in human spinal cord injury trials.

Study Design: This is a focused review article.

Objectives: This review presents important features of clinical outcomes assessments (COAs) in human spinal cord injury research. Considerations for COAs by trial phase and International Classification of Functioning, Disability and Health are presented as well as strengths and recommendations for upper extremity COAs for research.

Evidence-based scientific exercise guidelines for adults with spinal cord injury: an update and a new guideline.

Objectives: To describe the process and outcomes of using a new evidence base to develop scientific guidelines that specify the type and minimum dose of exercise necessary to improve fitness and cardiometabolic health in adults with spinal cord injury (SCI).

Setting: International.

Methods: Using Appraisal of Guidelines, Research and Evaluation (AGREE) II reporting criteria, steps included (a) determining the guidelines' scope; (b) conducting a systematic review of relevant literature; (c) holding three consensus panel meetings (European, Canadian and International) to formulate the guidelines; (d) obtaining stakeholder feedback; and (e) process evaluation by an AGREE II consultant.

Autoregressive transitional ordinal model to test for treatment effect in neurological trials with complex endpoints.

Background: A number of potential therapeutic approaches for neurological disorders have failed to provide convincing evidence of efficacy, prompting pharmaceutical and health companies to discontinue their involvement in drug development. Limitations in the statistical analysis of complex endpoints have very likely had a negative impact on the translational process.

Methods: We propose a transitional ordinal model with an autoregressive component to overcome previous limitations in the analysis of Upper Extremity Motor Scores, a relevant endpoint in the field of Spinal Cord Injury.

Bench to bedside: challenges of clinical translation.

Translating a scientific discovery from the laboratory to human application involves a series of challenges. Each requirement must be satisfactorily answered before moving to the next phase. Initially, there are several issues associated with the reproducibility of the original discovery.

Identifying Homogeneous Subgroups in Neurological Disorders: Unbiased Recursive Partitioning in Cervical Complete Spinal Cord Injury.

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.

Differences in spinothalamic function of cervical and thoracic dermatomes: insights using contact heat evoked potentials.

Introduction: After spinal cord injury, contact heat evoked potentials (CHEPs) may represent a means to refine the clinical assessment of sensory function from each spinal cord segment by quantifying nociception, including conduction along the spinothalamic tract.

Methods: The influence of stimulation site (i.e.

Outcome Measures for Acute/Subacute Cervical Sensorimotor Complete (AIS-A) Spinal Cord Injury During a Phase 2 Clinical Trial.

Effective treatment after cervical spinal cord injury (SCI) is imperative as so many activities of daily living (ADLs) are dependent on functional recovery of arm and hand actions. We focus on defining and comparing neurological and functional endpoints that might be used during acute or subacute Phase 2 clinical trials involving subjects with cervical sensorimotor complete SCI (ASIA Impairment Scale [AIS-A]). For the purposes of this review, the trial would examine the effects of a pharmaceutical small molecule, drug, biologic, or cell transplant on spinal tissue.

Improving the acquisition of nociceptive evoked potentials without causing more pain.

Following nociceptive heat or laser stimulation, an early contralateral and later vertex potential can be recorded. Although more indicative of the nociceptive input, the acquisition of the contralateral N1 after contact heat stimulation (contact heat-evoked potentials [CHEPs]) remains difficult. An advantage of contact heat is that the baseline skin temperature preceding peak stimulation can be controlled.

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).

Functional motor preservation below the level of injury in subjects with American Spinal Injury Association Impairment Scale grade A spinal cord injuries.

Objective: To assess how frequently subjects with spinal cord injuries (SCIs) classified as American Spinal Injury Association Impairment Scale (AIS) grade A have substantial preserved motor function below the neurologic level of injury, despite having no preserved sensory or motor function at the S4-5 spinal cord segment.

Design: Analysis of the European Multicenter Study about Spinal Cord Injury database to determine how frequently subjects assessed as AIS A would have been AIS D based on motor scores alone (ie, had scores of ≥3 in at least half of the International Standards for Neurological Classification of Spinal Cord Injury [ISNCSCI] key muscles below the neurologic level of injury, despite having no sacral sparing).

Setting: Eighteen European centers.

Computer vision-based classification of hand grip variations in neurorehabilitation.

The complexity of hand function is such that most existing upper limb rehabilitation robotic devices use only simplified hand interfaces. This is in contrast to the importance of the hand in regaining function after neurological injury. Computer vision technology has been used to identify hand posture in the field of Human Computer Interaction, but this approach has not been translated to the rehabilitation context.

Effect of a robotic rehabilitation device on upper limb function in a sub-acute cervical spinal cord injury population.

Robotic rehabilitation devices have been suggested as a tool to increase the amount of rehabilitation delivered after a neurological injury. Clinical robotic rehabilitation studies of the upper extremity have generally focused on stroke survivors. We present the results of a multi-center pilot study where an upper-limb robotic rehabilitation device (Armeo Spring®, Hocoma AG) was incorporated into the rehabilitation program of 12 subjects with sub-acute cervical spinal cord injury (motor level C4-C6, AIS A-D).

Traversing the translational trail for trials.

The principles of spinal cord injury clinical trial programs are briefly reviewed as one example of the challenge faced by most human studies of neurologically directed therapeutic interventions, including rehabilitation strategies. Different trial protocols are reviewed, as are inclusion/exclusion criteria for study subjects, the choice of clinical endpoints, and the statistical approaches that might be used in a trial program. Potential factors that might confound the accurate interpretation of trial data are also identified.

Muscle tension estimation in the presence of neuromuscular impairment.

Static optimization approaches to estimating muscle tensions rely on the assumption that the muscle activity pattern is in some sense optimal. However, in the case of individuals with a neuromuscular impairment, this assumption is likely not to hold true. We present an approach to muscle tension estimation that does not rely on any optimality assumptions.