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.

Neuromodulation with transcutaneous spinal stimulation reveals different groups of motor profiles during robot-guided stepping in humans with incomplete spinal cord injury.

Neuromodulation via spinal stimulation has been investigated for improving motor function and reducing spasticity after spinal cord injury (SCI) in humans. Despite the reported heterogeneity of outcomes, few investigations have attempted to discern commonalities among individual responses to neuromodulation, especially the impact of stimulation frequencies. Here, we examined how exposure to continuous lumbosacral transcutaneous spinal stimulation (TSS) across a range of frequencies affects robotic torques and EMG patterns during stepping in a robotic gait orthosis on a motorized treadmill. We studied nine chronic motor-incomplete SCI individuals (8/1 AIS-C/D, 8 men) during robot-guided stepping with body-weight support without and with TSS applied at random frequencies between 1 and up to 100 Hz at a constant, individually selected stimulation intensity below the common motor threshold for posterior root reflexes. The hip and knee robotic torques needed to maintain the predefined stepping trajectory and EMG in eight bilateral leg muscles were recorded. We calculated the standardized mean difference between the stimulation conditions grouped into frequency bins and the no stimulation condition to determine changes in the normalized torques and the average EMG envelopes. We found heterogeneous changes in robotic torques across individuals. Agglomerative clustering of robotic torques identified four groups wherein the patterns of changes differed in magnitude and direction depending mainly on the stimulation frequency and stance/swing phase. On one end of the spectrum, the changes in robotic torques were greater with increasing stimulation frequencies (four participants), which coincided with a decrease in EMG, mainly due to the reduction of clonogenic motor output in the lower leg muscles. On the other end, we found an inverted u-shape change in torque over the mid-frequency range along with an increase in EMG, reflecting the augmentation of gait-related physiological (two participants) or pathophysiological (one participant) output. We conclude that TSS during robot-guided stepping reveals different frequency-dependent motor profiles among individuals with chronic motor incomplete SCI. This suggests the need for a better understanding and characterization of motor control profiles in SCI when applying TSS as a therapeutic intervention for improving gait.

Soleus H and Lower Limb Posterior Root Muscle Reflexes During Stepping After Incomplete SCI.

The goal of this study was to examine and compare the step cycle related modulation of the soleus H and posterior root muscle (PRM) reflexes in subjects with and without spinal cord injury. Ten subjects without neurological injury and fifteen subjects with spinal cord injury (SCI) underwent soleus H reflex and lower limb PRM reflex testing while standing and stepping in a robotic gait orthosis. Reflex amplitudes were evaluated during standing, mid stance and mid swing to determine if speed and/or injury altered step cycle related neuromodulation. H and PRM reflexes in the soleus underwent step cycle related modulation in injured and uninjured subjects though the degree of modulation differed between the two reflexes with the H reflex showing more step cycle related modulation. We found in the SCI group that both the soleus H and soleus PRM reflex amplitudes were higher relative to the non-injured group and modulated less during the step cycle. We also found that modulation of the soleus H reflex, but not soleus PRM reflex, correlated to the lower extremity motor scores in individuals with SCI. Our evidence suggests that the inability to provide appropriate step cycle related reflex modulation may be due to decreased supra-spinal regulation of motoneuron and spinal excitability and could be an indicator of the severity of injury as it relates to clinically measured lower extremity motor scores.

Deleterious effects of whole-body vibration on the spine: A review of in vivo, ex vivo, and in vitro models.

Occupational exposure to whole-body vibration is associated with the development of musculoskeletal, neurological, and other ailments. Low back pain and other spine disorders are prevalent among those exposed to whole-body vibration in occupational and military settings. Although standards for limiting exposure to whole-body vibration have been in place for decades, there is a lack of understanding of whole-body vibration-associated risks among safety and healthcare professionals. Consequently, disorders associated with whole-body vibration exposure remain prevalent in the workforce and military. The relationship between whole-body vibration and low back pain in humans has been established largely through cohort studies, for which vibration inputs that lead to symptoms are rarely, if ever, quantified. This gap in knowledge highlights the need for the development of relevant in vivo, ex vivo, and in vitro models to study such pathologies. The parameters of vibrational stimuli (eg, frequency and direction) play critical roles in such pathologies, but the specific cause-and-effect relationships between whole-body vibration and spinal pathologies remain mostly unknown. This paper provides a summary of whole-body vibration parameters; reviews in vivo, ex vivo, and in vitro models for spinal pathologies resulting from whole-body vibration; and offers suggestions to address the gaps in translating injury biomechanics data to inform clinical practice.

Differential cardiovascular responses to cutaneous afferent subtypes in a nociceptive intersegmental spinal reflex.

Electrical stimulation to segmental dorsal cutaneous nerves (DCNs) activates a nociceptive sensorimotor reflex and the same afferent stimulation also evokes blood pressure (BP) and heart rate (HR) responses in rats. To investigate the relationship between those cardiovascular responses and the activation of nociceptive afferents, we analyzed BP and HR responses to electrical stimulations at each DCN from T6 to L1 at 0.5 mA to activate A-fiber alone or 5 mA to activate both A- and C-fibers at different frequencies. Evoked cardiovascular responses showed a decrease and then an increase in BP and an increase and then a plateau in HR. Segmentally, both cardiovascular responses tended to be larger when evoked from the more rostral DCNs. Stimulation frequency had a larger effect on cardiovascular responses than the rostrocaudal level of the DCN input. Stimulation strength showed a large effect on BP changes dependent on C-fibers whereas HR changes were dependent on A-fibers. Additional A-fiber activation by stimulating up to 4 adjacent DCNs concurrently, but only at 0.5 mA, affected HR but not BP. These data support that cutaneous nociceptive afferent subtypes preferentially contribute to different cardiovascular responses, A-fibers to HR and C-fibers to BP, with temporal (stimulation frequency) and spatial (rostrocaudal level) dynamics.

Central Plasticity of Cutaneous Afferents Is Associated with Nociceptive Hyperreflexia after Spinal Cord Injury in Rats.

Electrical stimulations of dorsal cutaneous nerves (DCNs) at each lumbothoracic spinal level produce the bilateral cutaneus trunci muscle (CTM) reflex responses which consist of two temporal components: an early and late responses purportedly mediated by Aδ and C fibers, respectively. We have previously reported central projections of DCN A and C fibers and demonstrated that different projection patterns of those afferent types contributed to the somatotopic organization of CTM reflex responses. Unilateral hemisection spinal cord injury (SCI) was made at T10 spinal segments to investigate the plasticity of early and late CTM responses 6 weeks after injury. Both early and late responses were drastically increased in response to both ipsi- and contralateral DCN stimulations both above (T6 and T8) and below (T12 and L1) the levels of injury demonstrating that nociceptive hyperreflexia developed at 6 weeks following hemisection SCI. We also found that DCN A and C fibers centrally sprouted, expanded their projection areas, and increased synaptic terminations in both T7 and T13, which correlated with the size of hemisection injury. These data demonstrate that central sprouting of cutaneous afferents away from the site of injury is closely associated with enhanced responses of intraspinal signal processing potentially contributing to nociceptive hyperreflexia following SCI.

Application of electrophysiological measures in spinal cord injury clinical trials: a narrative review.

STUDY DESIGN: Narrative review. OBJECTIVES: To discuss how electrophysiology may contribute to future clinical trials in spinal cord injury (SCI) in terms of: (1) improvement of SCI diagnosis, patient stratification and determination of exclusion criteria; (2) the assessment of adverse events; and (3) detection of therapeutic effects following an intervention. METHODS: An international expert panel for electrophysiological measures in SCI searched and discussed the literature focused on the topic. RESULTS: Electrophysiology represents a valid method to detect, track, and quantify readouts of nerve functions including signal conduction, e.g., evoked potentials testing long spinal tracts, and neural processing, e.g., reflex testing. Furthermore, electrophysiological measures can predict functional outcomes and thereby guide rehabilitation programs and therapeutic interventions for clinical studies. CONCLUSION: Objective and quantitative measures of sensory, motor, and autonomic function based on electrophysiological techniques are promising tools to inform and improve future SCI trials. Complementing clinical outcome measures, electrophysiological recordings can improve the SCI diagnosis and patient stratification, as well as the detection of both beneficial and adverse events. Specifically composed electrophysiological measures can be used to characterize the topography and completeness of SCI and reveal neuronal integrity below the lesion, a prerequisite for the success of any interventional trial. Further validation of electrophysiological tools with regard to their validity, reliability, and sensitivity are needed in order to become routinely applied in clinical SCI trials.

Temporal and spatial dynamics of spinal sensorimotor processing in an intersegmental cutaneous nociceptive reflex.

The cutaneus trunci muscle (CTM) reflex produces a skin "shrug" in response to pinch on a rat's back through a three-part neural circuit: 1) A-fiber and C-fiber afferents in segmental dorsal cutaneous nerves (DCNs) from lumbar to cervical levels, 2) ascending propriospinal interneurons, and 3) the CTM motoneuron pool located at the cervicothoracic junction. We recorded neurograms from a CTM nerve branch in response to electrical stimulation. The pulse trains were delivered at multiple DCNs (T6-L1), on both sides of the midline, at two stimulus strengths (0.5 or 5 mA, to activate Aδ fibers or Aδ and C fibers, respectively) and four stimulation frequencies (1, 2, 5, or 10 Hz) for 20 s. We quantified both the temporal dynamics (i.e., latency, sensitization, habituation, and frequency dependence) and the spatial dynamics (spinal level) of the reflex. The evoked responses were time-windowed into Early, Mid, Late, and Ongoing phases, of which the Mid phase, between the Early (Aδ fiber mediated) and Late (C fiber mediated) phases, has not been previously identified. All phases of the response varied with stimulus strength, frequency, history, and DCN level/side stimulated. In addition, we observed nociceptive characteristics like C fiber-mediated sensitization (wind-up) and habituation. Finally, the range of latencies in the ipsilateral responses were not very large rostrocaudally, suggesting a myelinated neural path within the ipsilateral spinal cord for at least the A fiber-mediated Early-phase response. Overall, these results demonstrate that the CTM reflex shares the temporal dynamics in other nociceptive reflexes and exhibits spatial (segmental and lateral) dynamics not seen in those reflexes.NEW & NOTEWORTHY We have physiologically studied an intersegmental reflex exploring detailed temporal, stimulus strength-based, stimulation history-dependent, lateral and segmental quantification of the reflex responses to cutaneous nociceptive stimulations. We found several physiological features in this reflex pathway, e.g., wind-up, latency changes, and somatotopic differences. These physiological observations allow us to understand how the anatomy of this reflex may be organized. We have also identified a new phase of this reflex, termed the "mid" response.

Comparison of peak oxygen consumption response to aquatic and robotic therapy in individuals with chronic motor incomplete spinal cord injury: a randomized controlled trial.

STUDY DESIGN: Randomized dual center controlled clinical trial. OBJECTIVE: To determine and compare the cardiorespiratory impact of 3 months of aquatic and robotic therapy for individuals with chronic motor incomplete spinal cord injury (CMISCI). SETTINGS: Two rehabilitation specialty hospitals. METHODS: Thirty-one individuals with CMISCI with neurological level between C2-T12 at least 1 year post injury were randomized to either aquatic or robotic treadmill therapy for 36 sessions. Customized sessions lasted 40-45 min at 65-75% heart rate reserve intensity with peak oxygen consumption (peak VO2) measured during arm ergometry at baseline and post intervention. Additional peak robotic treadmill VO2 assessments were obtained before and after training for participants randomized to robotic intervention. RESULTS: Peak VO2 measured with arm ergometry was not significantly different with either aquatic intervention (8.1%, p = 0.14, n = 15) or robotic intervention (-0.7%, p = 0.31, n = 17). Peak VO2 measured with robotic treadmill ergometry demonstrated a statistical improvement (14.7%, p = 0.03, n = 17, two-tailed t-test) across the robotic intervention. Comparison between the two interventions demonstrated a trend favoring aquatic therapy for improving arm ergometry peak VO2 (ANOVA, p = 0.063). CONCLUSIONS: Neither 3-month exercise interventions statistically improved arm cycle ergometry peak VO2, our cardiorespiratory surrogate marker, although percent improvement was greater in the aquatic exercise condition. Robotic ergometry peak VO2 did improve for the robotic intervention, confirming previous work. These results suggest that either intervention may hold utility in improving cardiorespiratory fitness in CMISCI, but peak VO2 measurement technique appears critical in detecting effects. SPONSORSHIP: DOD CDMRP SCI Research Program Clinical Trial Award SC090147, FY 2009. This study is registered under ClinicalTrials.gov Identifier: NCT01407354.

Data mining the effects of testing conditions and specimen properties on brain biomechanics.

Traumatic brain injury is highly prevalent in the United States. However, despite its frequency and significance, there is little understanding of how the brain responds during injurious loading. A confounding problem is that because testing conditions vary between assessment methods, brain biomechanics cannot be fully understood. Data mining techniques, which are commonly used to determine patterns in large datasets, were applied to discover how changes in testing conditions affect the mechanical response of the brain. Data at various strain rates were collected from published literature and sorted into datasets based on strain rate and tension vs. compression. Self-organizing maps were used to conduct a sensitivity analysis to rank the testing condition parameters by importance. Fuzzy C-means clustering was applied to determine if there were any patterns in the data. The parameter rankings and clustering for each dataset varied, indicating that the strain rate and type of deformation influence the role of these parameters in the datasets.

Lower extremity outcome measures: considerations for clinical trials in spinal cord injury.

STUDY DESIGN: This is a focused review article. OBJECTIVES: To identify important concepts in lower extremity (LE) assessment with a focus on locomotor outcomes and provide guidance on how existing outcome measurement tools may be best used to assess experimental therapies in spinal cord injury (SCI). The emphasis lies on LE outcomes in individuals with complete and incomplete SCI in Phase II-III trials. METHODS: This review includes a summary of topics discussed during a workshop focusing on LE function in SCI, conceptual discussion of corresponding outcome measures and additional focused literature review. RESULTS: There are a number of sensitive, accurate, and responsive outcome tools measuring both quantitative and qualitative aspects of LE function. However, in trials with individuals with very acute injuries, a baseline assessment of the primary (or secondary) LE outcome measure is often not feasible. CONCLUSION: There is no single outcome measure to assess all individuals with SCI that can be used to monitor changes in LE function regardless of severity and level of injury. Surrogate markers have to be used to assess LE function in individuals with severe SCI. However, it is generally agreed that a direct measurement of the performance for an appropriate functional activity supersedes any surrogate marker. LE assessments have to be refined so they can be used across all time points after SCI, regardless of the level or severity of spinal injury. SPONSORS: Craig H. Neilsen Foundation, Spinal Cord Outcomes Partnership Endeavor.

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. Clinical trial tools and designs to address recruitment challenges are identified. METHODS: The methods include a summary of topics discussed during a two-day workshop, conceptual discussion of upper extremity COAs and additional focused literature review. RESULTS: COAs must be appropriate to trial phase and particularly in mid-late-phase trials, should reflect recovery vs. compensation, as well as being clinically meaningful. The impact and extent of upper vs. lower motoneuron disease should be considered, as this may affect how an individual may respond to a given therapeutic. For trials with broad inclusion criteria, the content of COAs should cover all severities and levels of SCI. Specific measures to assess upper extremity function as well as more comprehensive COAs are under development. In addition to appropriate use of COAs, methods to increase recruitment, such as adaptive trial designs and prognostic modeling to prospectively stratify heterogeneous populations into appropriate cohorts should be considered. CONCLUSIONS: With an increasing number of clinical trials focusing on improving upper extremity function, it is essential to consider a range of factors when choosing a COA. SPONSORS: Craig H. Neilsen Foundation, Spinal Cord Outcomes Partnership Endeavor.

Rehabilitation research at the National Institutes of Health moving the field forward (executive summary).

Approximately 53 million Americans live with a disability. For decades, the National Institutes of Health (NIH) has been conducting and supporting research to discover new ways to minimize disability and enhance the quality of life of people with disabilities. After the passage of the Americans With Disabilities Act, NIH established the National Center for Medical Rehabilitation Research, with the goal of developing and implementing a rehabilitation research agenda. Currently, 17 institutes and centers at NIH invest more than $500 million per year in rehabilitation research. Recently, the director of NIH, Francis Collins, appointed a Blue Ribbon Panel to evaluate the status of rehabilitation research across institutes and centers. As a follow-up to the work of that panel, NIH recently organized a conference, "Rehabilitation Research at NIH: Moving the Field Forward." This report is a summary of the discussions and proposals that will help guide rehabilitation research at NIH in the near future. (PsycINFO Database Record

Rehabilitation Research at the National Institutes of Health:: Moving the Field Forward (Executive Summary).

Approximately 53 million Americans live with a disability. For decades, the National Institutes of Health (NIH) has been conducting and supporting research to discover new ways to minimize disability and enhance the quality of life of people with disabilities. After the passage of the American With Disabilities Act, the NIH established the National Center for Medical Rehabilitation Research with the goal of developing and implementing a rehabilitation research agenda. Currently, a total of 17 institutes and centers at NIH invest more than $500 million per year in rehabilitation research. Recently, the director of NIH, Dr Francis Collins, appointed a Blue Ribbon Panel to evaluate the status of rehabilitation research across institutes and centers. As a follow-up to the work of that panel, NIH recently organized a conference under the title "Rehabilitation Research at NIH: Moving the Field Forward." This report is a summary of the discussions and proposals that will help guide rehabilitation research at NIH in the near future.This article is being published almost simultaneously in the following six journals: American Journal of Occupational Therapy, American Journal of Physical Medicine and Rehabilitation, Archives of Physical Medicine and Rehabilitation, Neurorehabilitation and Neural Repair, Physical Therapy, and Rehabilitation Psychology. Citation information is as follows: Frontera WR, Bean JF, Damiano D, et al. Am J Phys Med Rehabil. 2017;97(4):393-403.

Rehabilitation Research at the National Institutes of Health: Moving the Field Forward (Executive Summary).

Approximately 53 million Americans live with a disability. For decades, the National Institutes of Health (NIH) has been conducting and supporting research to discover new ways to minimize disability and enhance the quality of life of people with disabilities. After the passage of the Americans With Disabilities Act, NIH established the National Center for Medical Rehabilitation Research, with the goal of developing and implementing a rehabilitation research agenda. Currently, 17 institutes and centers at NIH invest more than $500 million per year in rehabilitation research. Recently, the director of NIH, Francis Collins, appointed a Blue Ribbon Panel to evaluate the status of rehabilitation research across institutes and centers. As a follow-up to the work of that panel, NIH recently organized a conference, "Rehabilitation Research at NIH: Moving the Field Forward." This report is a summary of the discussions and proposals that will help guide rehabilitation research at NIH in the near future.