Edelle C. Field-Fote

Priming Neural Circuits to Modulate Spinal Reflex Excitability

While priming is most often thought of as a strategy for modulating neural excitability to facilitate voluntary motor control, priming stimulation can also be utilized to target spinal reflex excitability. In this application, priming can be used to modulate the involuntary motor output that often follows central nervous system injury. Individuals with spinal cord injury (SCI) often experience spasticity, for which antispasmodic medications are the most common treatment. Physical therapeutic/electroceutic interventions offer an alternative treatment for spasticity, without the deleterious side effects that can accompany pharmacological interventions. While studies of physical therapeutic/electroceutic interventions have been published, a systematic comparison of these approaches has not been performed. The purpose of this study was to compare four non-pharmacological interventions to a sham-control intervention to assess their efficacy for spasticity reduction. Participants were individuals (nu2009=u200910) with chronic SCI (≥1u2009year) who exhibited stretch-induced quadriceps spasticity. Spasticity was quantified using the pendulum test before and at two time points after (immediate, 45u2009min delayed) each of four different physical therapeutic/electroceutic interventions, plus a sham-control intervention. Interventions included stretching, cyclic passive movement (CPM), transcutaneous spinal cord stimulation (tcSCS), and transcranial direct current stimulation (tDCS). The sham-control intervention consisted of a brief ramp-up and ramp-down of knee and ankle stimulation while reclined with legs extended. The order of interventions was randomized, and each was tested on a separate day with at least 48u2009h between sessions. Compared to the sham-control intervention, stretching, CPM, and tcSCS were associated with a significantly greater reduction in spasticity immediately after treatment. While the immediate effect was largest for stretching, the reduction persisted for 45u2009min only for the CPM and tcSCS interventions. tDCS had no immediate or delayed effects on spasticity when compared to sham-control. Interestingly, the sham-control intervention was associated with significant within-session increases in spasticity, indicating that spasticity increases with immobility. These findings suggest that stretching, CPM, and tcSCS are viable non-pharmacological alternatives for reducing spasticity, and that CPM and tcSCS have prolonged effects. Given that the observed effects were from a single-session intervention, future studies should determine the most efficacious dosing and timing strategies.

The experience of spasticity after spinal cord injury: perceived characteristics and impact on daily life

Study designCross-sectional survey.ObjectivesDetermine the impact of motor control characteristics attributed to spasticity, such as spasms, stiffness, and clonus on the daily life of people with spinal cord injury (SCI).SettingNationwide, United States.MethodsInternet-administered questionnaire, the Patient Reported Impact of Spasticity Measure (PRISM) and items describing characteristics of spasticity including stiffness, spasms, clonus, and pain.ResultsOf the 145 respondents, 113 (78%) reported a PRISM score of at least 5/164, indicating spasticity had some impact on their daily lives. Stiffness impact was highly correlated (ρu2009=u20090.84; pu2009<u20090.01) with the PRISM negative impact on Daily Activities subscale and moderately correlated with the other PRISM subscales (ρu2009=u20090.55–0.63; pu2009<u20090.01). Spasm presence had a negligible or low correlation with PRISM negative impact subscales (ρu2009=u20090.29–0.47; pu2009<u20090.01). Trunk muscle stiffness and spasms had a low correlation with PRISM Need for Assistance and Daily activities (ρu2009=u20090.42 and ρu2009=u20090.41, pu2009<u20090.01, respectively). Anti-spasticity medications were ineffective for 58% of respondents. Pain in the legs was reported by 57% of respondents.ConclusionsThe experience of spasticity is highly individualized, and is often distributed differently across arms, trunk, and legs. Despite the fact that traditional definitions of spasticity focus on reflex responsiveness, the stiffness associated with spasticity appears to be more problematic than spasms or clonus. The self-described characteristics of spasticity and its physiological presentation are complex and related to pain. This varied presentation lends support to the concept that management of spasticity may be best achieved by multimodality strategies.

Dose-Response Outcomes Associated with Different Forms of Locomotor Training in Persons with Chronic Motor-Incomplete Spinal Cord Injury.

Outcomes of training are thought to be related to the amount of training (training dose). Although various approaches to locomotor training have been used to improve walking function in persons with spinal cord injury (SCI), little is known about the relationship between dose of locomotor training and walking outcomes. This secondary analysis aimed to identify the relationship between training dose and improvement in walking distance and speed associated with locomotor training in participants with chronic motor-incomplete spinal cord injury (MISCI). We compared the dose-response relationships associated with each of four different locomotor training approaches. Participants were randomized to either: treadmill-based training with manual assistance (TMu2009=u200917), treadmill-based training with stimulation (TSu2009=u200918), overground training with stimulation (OGu2009=u200915), and treadmill-based training with locomotor robotic device assistance (LRu2009=u200914). Subjects trained 5 days/week for 12 weeks, with a target of 60 training sessions. The distance-dose and time-dose were calculated based on the total distance and total time, respectively, participants engaged in walking over all sessions combined. Primary outcome measures included walking distance (traversed in 2u2009min) and walking speed (over 10u2009m). Only OG training showed a good correlation between distance-dose and change in walking distance and speed walked over ground (ru2009=u20090.61, pu2009=u20090.02; ru2009=u20090.62, pu2009=u20090.01). None of the treadmill-based training approaches were associated with significant correlations between training dose and improvement of functional walking outcome. The findings suggest that greater distance achieved over the course of OG training is associated with better walking outcomes in the studied population. Further investigation to identify the essential elements that determine outcomes would be valuable for guiding rehabilitation.

Comparison of Single-Session Dose Response Effects of Whole Body Vibration on Spasticity and Walking Speed in Persons with Spinal Cord Injury

Spasticity affects approximately 65% of persons with spinal cord injury (SCI) and negatively impacts function and quality of life. Whole body vibration (WBV) appears to reduce spasticity and improve walking function; however, the optimal dose (frequency/duration) is not known. We compared single-session effects of four different WBV frequency/duration dose conditions on spasticity and walking speed, in preparation for a planned multi-session study. Thirty-five participants with motor-incomplete SCI received four different doses of WBV: high frequency (50xa0Hz)/short duration (180xa0s), high frequency/long duration (360xa0s), low frequency (30xa0Hz)/short duration, and low frequency/long duration, plus a control intervention consisting of sham electrical stimulation. In all conditions, participants stood on the WBV platform for 45-s bouts with 1xa0min rest between bouts until the requisite duration was achieved. The frequency/duration dose order was randomized across participants; sessions were separated by at least 1xa0week. Quadriceps spasticity was measured using the pendulum test at four time points during each session: before, immediately after, 15xa0min after, and 45xa0min after WBV. Walking speed was quantified using the 10-m walk test at three time points during each session: baseline, immediately after, and 45xa0min after WBV. In the full group analysis, no frequency/duration combination was significantly different from the sham-control condition. In participants with more severe spasticity, a greater reduction in stretch reflex excitability was associated with the high frequency/long duration WBV condition. The sham-control condition was associated with effects, indicating that the activity of repeated sitting and standing may have a beneficial influence on spasticity. Trial registration: NCT02340910 (assigned 01/19/2015).

Impact of spasticity on transfers and activities of daily living in individuals with spinal cord injury

Context/Objective: For persons with spinal cord injury, spasticity commonly interferes with activities of daily living such as transfers. Electromyography can be used to objectively measure muscle spasms during transfers, but how electromyographic measures relate to the impact spasticity has on life, or to clinically-rated spasticity, is unclear. We aimed to characterize relationships among spasm duration and magnitude, impact of spasticity on daily life, and a clinical measure of extensor spasticity, as well as to determine reliability of the electromyographic measures. Design: Participants (N=19) underwent electromyographic measurements of involuntary muscle activity (spasm duration and magnitude) evoked in quadriceps muscles during transfers on two days. Impact of spasticity on daily life was measured with the Spinal Cord Injury Spasticity Evaluation Tool. Clinically-rated spasticity severity was measured with the Spinal Cord Assessment Tool for Spastic reflexes. Results: No significant associations were found between impact of spasticity and spasm duration, spasm magnitude, or clinical extensor spasticity score. Absolute and normalized spasm duration were positively associated with clinical extensor spasticity score (rho=0.510-0.667, Pu2009<u20090.05). Spasm measures during transfers had good to excellent day-to-day reliability (rho=0.656-0.846, Pu2009<u20090.05). Conclusions: Electromyographic and clinical measures of involuntary activity in the lower extremity do not significantly relate to perceived impact of spasticity on daily life. However, quadriceps spasm duration during transfers is related to clinically-rated extensor spasticity. Electromyography is a reliable method of quantifying quadriceps spasms during transfers. Future investigations should identify factors that influence the impact of spasticity on life, which may help direct treatment strategies to reduce problematic impact.

Priming for Improved Hand Strength in Persons with Chronic Tetraplegia: A Comparison of Priming-Augmented Functional Task Practice, Priming Alone, and Conventional Exercise Training

Many everyday tasks cannot be accomplished without adequate grip strength, and corticomotor drive to the spinal motoneurons is a key determinant of grip strength. In persons with tetraplegia, damage to spinal pathways limits transmission of signals from motor cortex to spinal motoneurons. Corticomotor priming, which increases descending drive, should increase corticospinal transmission through the remaining spinal pathways resulting in increased grip strength. Since the motor and somatosensory cortices share reciprocal connections, corticomotor priming may also have potential to influence somatosensory function. The purpose of this study was to assess changes in grip (precision, power) force and tactile sensation associated with two different corticomotor priming approaches and a conventional training approach and to determine whether baseline values can predict responsiveness to training. Participants with chronic (≥1u2009year) tetraplegia (nu2009=u200949) were randomized to one of two corticomotor priming approaches: functional task practice plus peripheral nerve somatosensory stimulation (FTPu2009+u2009PNSS) or PNSS alone, or to conventional exercise training (CET). To assess whether baseline corticospinal excitability (CSE) is predictive of responsiveness to training, in a subset of participants, we assessed pre-intervention CSE of the thenar muscles. Participants were trained 2u2009h daily, 5u2009days/week for 4u2009weeks. Thirty-seven participants completed the study. Following intervention, significant improvements in precision grip force were observed in both the stronger and weaker hand in the FTPu2009+u2009PNSS group (effect size: 0.51, pu2009=u20090.04 and 0.54, pu2009=u20090.03, respectively), and significant improvements in weak hand precision grip force were associated with both PNSS and CET (effect size: 0.54, pu2009=u20090.03 and 0.75, pu2009=u20090.02, respectively). No significant changes were observed in power grip force or somatosensory scores in any group. Across all groups, responsiveness to training as measured by change in weak hand power grip force was correlated with baseline force. Change in precision grip strength was correlated with measures of baseline CSE. These findings indicate that corticomotor priming with FTPu2009+u2009PNSS had the greatest influence on precision grip strength in both the stronger and weaker hand; however, both PNSS and CET were associated with improved precision grip strength in the weaker hand. Responsiveness to training may be associated with baseline CSE.

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

Study designThis is a focused review article.ObjectivesThis 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.MethodsThe methods include a summary of topics discussed during a two-day workshop, conceptual discussion of upper extremity COAs and additional focused literature review.ResultsCOAs 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.ConclusionsWith 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.SponsorsCraig H. Neilsen Foundation, Spinal Cord Outcomes Partnership Endeavor.

Lymphedema techniques to manage edema after SCI: a retrospective analysis

Study designRetrospective analysis of treatment data for a cohort of clients with spinal cord injury (SCI) who received therapy for management of edema.ObjectiveTo evaluate the safety, feasibility, and benefit of a modified lymphedema treatment approach for treatment of chronic lower extremity edema in persons with SCI.SettingA specialty rehabilitation hospital in Atlanta, GA, USA.MethodsCertified lymphedema therapists with experience in SCI rehabilitation modified standard complete decongestive therapy (CDT) techniques to accommodate sensory and motor impairments and ensure skin safety. Therapists applied the modified CDT (mCDT) approach as part of treatment in 59 adults with SCI and lower extremity edema. Limb volume was measured using standardized volumetric measurement, pitting was scored using a standardized scale (range 0–4), and edema characteristics were determined to be present or absent. Outcomes of the mCDT intervention were analyzed for 105 lower extremities.ResultsOutcomes indicated that mCDT was associated with significant reduction in limb volumes, with a mean decrease of 11u2009±u20097.6%. Significant decreases were also observed in pitting edema and edema-specific characteristics, mean pitting scale score was reduced from a 3/4 to a 1/4. Minor adverse events were identified in a small number of patients.ConclusionsWe found the mCDT approach to be safe and well-tolerated by the patients with SCI. The intervention was associated with decreased edema, and was feasible for use in a clinical setting. We recommend considering this mCDT approach for management of edema in individuals with SCI, while remaining vigilant about skin inspection.

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

Study DesignThis is a focused review article.ObjectivesTo 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.MethodsThis 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.ResultsThere 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.ConclusionThere 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.SponsorsCraig H. Neilsen Foundation, Spinal Cord Outcomes Partnership Endeavor.

Neuromodulation in the restoration of function after spinal cord injury

Neuromodulation, the use of electrical interfaces to alter neuronal activity, has been successful as a treatment approach in several neurological disorders, including deep brain stimulation for Parkinsons disease and epidural spinal stimulation for chronic pain. Neuromodulation can also be beneficial for spinal cord injury, from assisting basic functions such as respiratory pacing and bladder control, through to restoring volitional movements and skilled hand function. Approaches range from electrical stimulation of peripheral muscles, either directly or via brain-controlled bypass devices, to stimulation of the spinal cord and brain. Limitations to widespread clinical application include durability of neuromodulation devices, affordability and accessibility of some approaches, and poor understanding of the underlying mechanisms. Efforts to overcome these challenges through advances in technology, together with pragmatic knowledge gained from clinical trials and basic research, could lead to personalised neuromodulatory interventions to meet the specific needs of individuals with spinal cord injury.