Julian Taylor

Impact of specific symptoms of spasticity on voluntary lower limb muscle function, gait and daily activities during subacute and chronic spinal cord injury

BACKGROUND Although the spasticity syndrome is an important sensorimotor disorder, the impact of grade of lower limb muscle hypertonia, spasm and clonus activity on voluntary muscle function, gait and daily activities has not been systematically analysed during subacute and chronic spinal cord injury (SCI). OBJECTIVE To determine the prevalence of spasticity signs and symptoms during SCI, and to assess their impact on motor function and activities. METHODS A descriptive transverse study of sixty-six subjects with SCI was performed by assessing injury characteristics, spasticity (modified Ashworth scale, Penn scale, SCATS scale) and motor function (lower limb manual muscle scores, WISCI II, spinal cord injury spasticity evaluation tool). RESULTS Most subjects with the spasticity syndrome presented lower limb hypertonia and spasms during both subacute and chronic SCI, interfering with daily life activities. Subjects with incomplete SCI and hypertonia revealed a loss of voluntary flexor muscle activity, while extensors spasms contributed strongly to loss of gait function. The Penn spasms scale no correlated with muscle function or gait. CONCLUSIONS Specific diagnosis of spasm activity during subacute SCI, and its impact on lower limb voluntary muscle activity, gait function and daily activities, is required to develop a more effective neurorehabilitation treatment strategy.

Spinal cord injury induced changes of nuclear receptors PPARα and LXRβ and modulation with oleic acid/albumin treatment

In previous studies with animal models of spinal cord injury (SCI) pharmacological activation of peroxisome proliferator activated receptors (PPAR) and liver X receptors (LXR) were used to reduce tissue damage and promote behavioral recovery in animal models. We have studied the endogenous expression of the transcription factors PPARα and LXRβ in the chronic stage after SCI in rats. The immunohistochemical investigation revealed a long lasting increase in the level of PPARα in white matter in the vicinity of the lesion site. The source of this signal was identified in a subpopulation of astrocytes outside of the glial scar area. Intrathecal injections of oleic acid/albumin reduced the lesion-induced PPARα immunoreactivity. In addition, ependymal cells displayed a prominent PPARα signal in the non-injured spinal cord, and continued to express the receptor as they proliferated and migrated within the damaged tissue. The nuclear receptor LXRβ was detected at similar levels after SCI as in sham operated animals. We found high levels of immunoreactivity in the gray matter, while in the white matter it was present in subpopulations of astrocytes and oligodendrocytes. Macrophages that had accumulated within the center of the lesion contained LXRβ in their cell nuclei. Possible endogenous functions of PPARα and LXRβ after SCI are discussed, specifically the control of fatty acid and cholesterol metabolism and the regulation of inflammatory reactions.

Muscle Synergies in Cycling after Incomplete Spinal Cord Injury: Correlation with Clinical Measures of Motor Function and Spasticity

Background: After incomplete spinal cord injury (iSCI), patients suffer important sensorimotor impairments, such as abnormal locomotion patterns and spasticity. Complementary to current clinical diagnostic procedures, the analysis of muscle synergies has emerged as a promising tool to study muscle coordination, which plays a major role in the control of multi-limb functional movements. Objective: Based on recent findings suggesting that walking and cycling share similar synergistic control, the analysis of muscle synergies during cycling might be explored as an early descriptor of gait-related impaired control. This idea was split into the following two hypotheses: (a) iSCI patients present a synergistic control of muscles during cycling; (b) muscle synergies outcomes extracted during cycling correlate with clinical measurements of gait performance and/or spasticity. Methods: Electromyographic (EMG) activity of 13 unilateral lower limb muscles was recorded in a group of 10 healthy individuals and 10 iSCI subjects during cycling at four different cadences. A non-negative matrix factorization (NNMF) algorithm was applied to identify synergistic components (i.e., activation coefficients and muscle synergy vectors). Reconstruction goodness scores (VAF and r2) were used to evaluate the ability of a given number of synergies to reconstruct the EMG signals. A set of metrics based on the similarity between pathologic and healthy synergies were correlated with clinical scales of gait performance and spasticity. Results: iSCI patients preserved a synergistic control of muscles during cycling. The similarity with the healthy reference was consistent with the degree of the impairment, i.e., less impaired patients showed higher similarities with the healthy reference. There was a strong correlation between reconstruction goodness scores at 42 rpm and motor performance scales (TUG, 10-m test and WISCI II). On the other hand, the similarity between the healthy and affected synergies presented correlation with some spasticity symptoms measured by Penn, Modified Ashworth and SCATS scales. Conclusion: Overall, the results of this study support the hypothesis that the analysis of muscle synergies during cycling can provide detailed quantitative assessment of functional motor impairments and symptoms of spasticity caused by abnormal spatiotemporal muscle co-activation following iSCI.

Principles of human locomotion: A review

In this article the principles of human locomotion are revisited and reviewed. This has been done in the framework of two European projects, where the elicitation of these mechanisms inform, on the one hand, the design of artificial bipedal walkers (H2R), and on the other hand the design of lower limb exoskeletons (BETTER) for rehabilitation of gait in post-stroke patients. Passive dynamics emerging from the morphology of the human musculoskeletal system, reflexes as stabilization mechanisms, modular control of movement as well as supra-spinal control of gait are reviewed to get insight on how these mechanisms can be used to explain human locomotion.

Maintenance of cutaneomuscular neuronal excitability after leg-cycling predicts lower limb muscle strength after incomplete spinal cord injury.

OBJECTIVE Controlled leg-cycling modulates H-reflex activity after spinal cord injury (SCI). Preserved cutaneomuscular reflex activity is also essential for recovery of residual motor function after SCI. Here the effect of a single leg-cycling session was assessed on cutaneomuscular-conditioned H-reflex excitability in relation to residual lower limb muscle function after incomplete SCI (iSCI). METHODS Modulation of Soleus H-reflex activity was evaluated following ipsilateral plantar electrical stimulation applied at 25-100ms inter-stimulus intervals (ISIs), before and after leg-cycling in ten healthy individuals and nine subjects with iSCI. RESULTS Leg-cycling in healthy subjects increased cutaneomuscular-conditioned H-reflex excitability between 25 and 75ms ISI (p<0.001), compared to a small loss of excitability at 75ms ISI after iSCI (p<0.05). In addition, change in cutaneomuscular-conditioned H-reflex excitability at 50ms and 75ms ISI in subjects with iSCI after leg-cycling predicted lower ankle joint hypertonia and higher Triceps Surae muscle strength, respectively. CONCLUSION Leg-cycling modulates cutaneomuscular-conditioned spinal neuronal excitability in healthy subjects and individuals with iSCI, and is related to residual lower limb muscle function. SIGNIFICANCE Cutaneomuscular-conditioned H reflex modulation could be used as a surrogate biomarker of both central neuroplasticity and lower limb muscle function, and could benchmark lower-limb rehabilitation programs in subjects with iSCI.

Abnormal cutaneous flexor reflex activity during controlled isometric plantarflexion in human spinal cord injury spasticity syndrome

Study design:Although abnormal cutaneous reflex (CR) activity has been identified during gait after incomplete spinal cord injury (SCI), this activity has not been directly compared in subjects with and without the spasticity syndrome.Objectives:Characterisation of CR activity during controlled rest and ‘ramp and hold’ phases of controlled plantarflexion in subjects with and without the SCI spasticity syndrome.Design:Transverse descriptive study with non-parametric group analysis.Setting:SCI rehabilitation hospital.Methods:Tibialis Anterior (TA) reflexes were evoked by innocuous cutaneous plantar sole stimulation during rest and ramp and hold phases of plantarflexion torque in non-injured subjects (n=10) and after SCI with (n=9) and without (n=10) hypertonia and/or involuntary spasm activity. Integrated TA reflex responses were analysed as total (50–300 ms) or short (50–200 ms) and long-latency (200–300 ms) activity.Results:Total and long-latency TA activity was inhibited in non-injured subjects and the SCI group without the spasticity syndrome during plantarflexion torque but not in the SCI spasticity group. Furthermore, loss of TA reflex inhibition during plantarflexion correlated with time after SCI (ρ=0.79, P=0.009). Moreover, TA reflex activity inversely correlated with maximum plantarflexion torque in the spasticity group (ρ=−0.75, P=0.02), despite similar non-reflex TA electromyographic activity during plantarflexion after SCI in subjects with (0.11, 0.08–0.13 mV) or without the spasticity syndrome (0.09, 0.07–0.12 mV).Conclusions:This reflex testing procedure supports previously published evidence for abnormal CR activity after SCI and may characterise the progressive disinhibition of TA reflex activity during controlled plantarflexion in subjects diagnosed with the spasticity syndrome.

The role of Omega-3 and Omega-9 fatty acids for the treatment of neuropathic pain after neurotrauma

Omega-3 polyunsaturated fatty acids (PUFAs), such as docosaexaenoic acid (DHA) and eicosapentaenoic acid (EPA), mediate neuroactive effects in experimental models of traumatic peripheral nerve and spinal cord injury. Cellular mechanisms of PUFAs include reduced neuroinflammation and oxidative stress, enhanced neurotrophic support, and activation of cell survival pathways. Bioactive Omega-9 monounsaturated fatty acids, such as oleic acid (OA) and 2-hydroxy oleic acid (2-OHOA), also show therapeutic effects in neurotrauma models. These FAs reduces noxious hyperreflexia and pain-related anxiety behavior following peripheral nerve injury and improves sensorimotor function following spinal cord injury (SCI), including facilitation of descending inhibitory antinociception. The relative safe profile of neuroactive fatty acids (FAs) holds promise for the future clinical development of these molecules as analgesic agents. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.

Effect of Unmodulated 5-kHz Alternating Currents Versus Transcutaneous Electrical Nerve Stimulation on Mechanical and Thermal Pain, Tactile Threshold, and Peripheral Nerve Conduction: A Double-Blind, Placebo-Controlled Crossover Trial

OBJECTIVE To investigate the effect of unmodulated 5-kHz alternating current on mechanical pain threshold (MPT), heat pain threshold (HPT), tactile threshold (TT), and peripheral nerve conduction (PNC) compared with transcutaneous electrical nerve stimulation (TENS) and sham stimulation. SETTING National referral center. DESIGN Randomized, double-blind, placebo-controlled crossover trial. PARTICIPANTS Healthy volunteers (N=38). No dropouts or adverse events were reported. INTERVENTION TENS, unmodulated 5-kHz currents, and sham stimulation were applied on the radial nerve for 20 minutes with a 24-hour washout period between them and concealed intervention allocation. MAIN OUTCOME MEASURES Four measures were taken: before, during, and 2 after the interventions. Algometry was used to assess MPT, a Peltier thermode for HPT using the method of limits, Von Frey filaments for TT, and radial nerve compound action potential. RESULTS No differences were observed on MPT, HPT, and PNC when 5-kHz current and TENS were compared. However, TT increased 56.2mN (95% confidence interval [CI], 28.8-83.6) in the TENS group compared with the 5-kHz current group during intervention. Compared with sham stimulation during intervention, MPT increased 4.7N (95% CI, 0.3-9.2) using 5-kHz current and 10.4N (95% CI, 3.5-17.3) with TENS. TT increased 17.2mN (95% CI, 4.7-29.7) with 5-kHz current and 73.4mN (95% CI, 47.5-99.2) with TENS. However, HPT increased 1.0°C (95% CI, 0.2-2.0) only with TENS. For the PNC, no differences were found among the 3 groups. CONCLUSIONS Unmodulated 5-kHz current produced an increase in somatosensory thresholds that was greater than placebo but not when compared with TENS; however, participants perceived 5-kHz currents to be more comfortable and showed more habituation to them.

Assessing sensorimotor excitability after spinal cord injury: a reflex testing method based on cycling with afferent stimulation

AbstractSeveral studies have examined spinal reflex modulation during leg cycling in healthy and spinal cord injury (SCI) subjects. However, the effect of cutaneous plantar afferent input on spinal excitability during leg cycling after SCI has not been characterised. The aim of the study was to test the feasibility of using controlled leg cycling in combination with plantar cutaneous electrical stimulation (ES) cycling to assess lower limb spinal sensorimotor excitability in subjects with motor complete or incomplete SCI. Spinal sensorimotor excitability was estimated by measuring cutaneomuscular-conditioned soleus H-reflex activity. Reflex excitability was tested before and after a 10-min ES cycling session in 13 non-injured subjects, 6 subjects with motor incomplete SCI (iSCI) who had moderately impaired gait function, 4 subjects with motor iSCI who had severely impaired gait function, and 5 subjects with motor complete SCI (cSCI). No modulation of soleus H-reflex with plantar cutaneous stimuli was observed after either iSCI or cSCI when compared to non-injured subjects. However, after ES cycling, reflex excitability significantly increased in subjects with iSCI and moderately impaired gait function. ES cycling facilitated spinal sensorimotor excitability only in subjects with motor iSCI with residual gait function. Increased spinal excitability induced with a combination of exercise and afferent stimulation could be adopted with diagnostic and prognostic purposes to reveal the activity-based neurorehabilitation profile of individual subjects with motor iSCI.Trial registration: ISRCTN26172500; retrospectively registered on 15 July 2016 Graphical abstractᅟ

Clinical Trial of the Soft Extra Muscle Glove to Assess Orthotic and Long-Term Functional Gain Following Chronic Incomplete Tetraplegia: Preliminary Functional Results

The soft extra muscle (SEM) Glove is a robotic hand device with the potential to serve as an orthotic and rehabilitation tool for people with spinal cord injury (SCI). In this longitudinal study 15 participants with a high neurological level (C2–C8) chronic SCI will be selected to trial the SEM Glove for 12 weeks at home to assist with activities of daily living (ADL). The participants will be scheduled to attend assessment sessions at Week 0 (Initial), Week 6, Week 12 and Week 18. Here we present progress with results related to grip strength and the Toronto Rehabilitation Institute hand function test (TRI-HFT) from eight participants who have completed the study. There was significant improvement in gross hand grip strength between Initial and Week 12 (p = 0.045). The TRI-HFT revealed significant improvement in hand function between Initial and, Week 6 (p ~ 0.01), Week 12 (p ~ 0.02). These results suggest that home use of devices designed to improve grip function has a direct effect on hand function.