Spinal Cord Injury Muscle Research Articles

Induced Muscle Fiber Regeneration In Permanent Skeletal Muscle Denervation: Implication For Functional Electrical Stimulation Of Denervated Degenerated Muscles In Spinal Cord Injury

Induced Muscle Fiber Regeneration In Permanent Skeletal Muscle Denervation: Implication For Functional Electrical Stimulation Of Denervated Degenerated Muscles In Spinal Cord Injury

Skeletal muscle hypertrophy and attenuation of cardio-metabolic risk factors (SHARC) using functional electrical stimulation-lower extremity cycling in persons with spinal cord injury: study protocol for a randomized clinical trial

BackgroundPersons with spinal cord injury (SCI) are at heightened risks of developing unfavorable cardiometabolic consequences due to physical inactivity. Functional electrical stimulation (FES) and surface neuromuscular electrical stimulation (NMES)-resistance training (RT) have emerged as effective rehabilitation methods that can exercise muscles below the level of injury and attenuate cardio-metabolic risk factors. Our aims are to determine the impact of 12 weeks of NMES + 12 weeks of FES-lower extremity cycling (LEC) compared to 12 weeks of passive movement + 12 weeks of FES-LEC on: (1) oxygen uptake (VO2), insulin sensitivity, and glucose disposal in adults with SCI; (2) skeletal muscle size, intramuscular fat (IMF), and visceral adipose tissue (VAT); and (3) protein expression of energy metabolism, protein molecules involved in insulin signaling, muscle hypertrophy, and oxygen uptake and electron transport chain (ETC) activities.Methods/DesignForty-eight persons aged 18–65 years with chronic (> 1 year) SCI/D (AIS A-C) at the C5-L2 levels, equally sub-grouped by cervical or sub-cervical injury levels and time since injury, will be randomized into either the NMES + FES group or Passive + FES (control group). The NMES + FES group will undergo 12 weeks of evoked RT using twice-weekly NMES and ankle weights followed by twice-weekly progressive FES-LEC for an additional 12 weeks. The control group will undergo 12 weeks of passive movement followed by 12 weeks of progressive FES-LEC. Measurements will be performed at baseline (B; week 0), post-intervention 1 (P1; week 13), and post-intervention 2 (P2; week 25), and will include: VO2 measurements, insulin sensitivity, and glucose effectiveness using intravenous glucose tolerance test; magnetic resonance imaging to measure muscle, IMF, and VAT areas; muscle biopsy to measure protein expression and intracellular signaling; and mitochondrial ETC function.DiscussionTraining through NMES + RT may evoke muscle hypertrophy and positively impact oxygen uptake, insulin sensitivity, and glucose effectiveness. This may result in beneficial outcomes on metabolic activity, body composition profile, mitochondrial ETC, and intracellular signaling related to insulin action and muscle hypertrophy. In the future, NMES-RT may be added to FES-LEC to improve the workloads achieved in the rehabilitation of persons with SCI and further decrease muscle wasting and cardio-metabolic risks.Trial registrationClinicalTrials.gov, NCT02660073. Registered on 21 Jan 2016.

Regeneration of Denervated Skeletal Muscles - Brunelli's CNS-PNS Paradigm.

The restoration of voluntary muscle activity in posttraumatic paraplegia in both animal experiments and other clinical applications requires reproducibility of a technically-demanding microsurgical procedure, limited by physicians’ understanding of Brunelli’s spinal cord grafting paradigm. The insufficient clinical investigation of the long-term benefits of the CNS-PNS graft application warrants additional inquiry.The objective of this study is to explore the potential benefits of the first replicated, graft-induced neuroregeneration of denervated skeletal muscle regarding long-term clinical outcomes and to investigate the effect of Cerebrolysin on neuromodulation.A randomized study evaluating 30 rats, approved by the National Animal Ethics Advisory Committee was performed. The medication was administered postoperatively. For 14 days, 12 rats received Cerebrolysin (serum), 11 received NaCl 0.9% (shams), and 7 were controls. For microsurgery, the lateral corticospinal tract T10 was grafted to the denervated internal obliquus abdominal muscle. On day 90, intraoperative proof of reinnervation was observed. On day 100, 15 rats were euthanized for fixation, organ removal, and extensive histology-morphology examination, and the Wei-Lachin statistical procedure was employed.After an open revision of 16 rats, 8 were CMAP positive. After intravenous Vecuronium application, two (Cerebrolysin, NaCl) out of two rats showed an incomplete compound muscle action potential (CMAP) loss due to glutamatergic and cholinergic co-transmission, while two others showed a complete loss of amplitude.Cerebrolysin medication initiated larger restored muscle fiber diameters and less scarring. FB+ neurons were not observed in the brain but were observed in the Rexed laminae.Brunelli’s concept was successfully replicated, demonstrating the first graft induced existence of cholinergic and glutamatergic neurotransmission in denervated grafted muscles. Statistics of the histometric count of muscle fibers revealed larger fiber diameters after Cerebrolysin.Brunelli’s CNS-PNS experimental concept is suitable to analyze graft-neuroplasticity focused on the voluntary restoration of denervated skeletal muscles in spinal cord injury. Neuroprotection by Cerebrolysin is demonstrated.

Local immunomodulation and muscle progenitor cells induce recovery in atrophied muscles in spinal cord injury patients

Objectives:Restore muscular trophism and voluntary contractile capacity through cell therapy in atrophied muscles in SCI patients.Setting:Out Patient Treatment, Universidad Maimonides, Buenos Aires, Argentina.Methods:After receiving spinal cord cell therapy and intensive rehabilitation, 7 chronic complete spinal cord injury (SCI) patients (4 people with paraplegia and 3 people with quadriplegia) regained muscular electrical activity in previously denervated territories. However, signs of severe muscular atrophy persisted. Looking to reverse chronic muscular atrophy, atrophied muscles with electrical activity were implanted with autologous type 1 macrophages (Mo1) and autologous tissue-specific T helper 1 Cells (Th1) associated with autologous muscular progenitor cells (MPC). The Mo1 and Th1 used cells were named Effector Cells (EC). Each muscle received between 6 to 8 implants, one every 6 weeks. Cellular therapy was combined with intensive rehabilitation program.Results:Sonogram and histological signs of recovery started eight weeks after the first implant. Sonograms showed progressively muscle volume increasing and gradually replacement of hyperechogenic muscle tissue by hypoechogenic muscle bands (resembling normal muscular structure). New bands were distributed parallel to the main muscle axis, along the entire muscular length. Histological samples of hypoechogenic bands showed new and normal muscular tissue. Changes were seen in 7/7 patients. Non-significant side events were detected in any patient over the 24 months of follow up.Conclusions:The results presented here suggest that the combination of immune and regenerative cell therapy may play an important therapeutic role in clinical and histological recovery of chronic muscular atrophy.

Musculoskeletal Health in the Context of Spinal Cord Injury

This review assembles recent understanding of the profound loss of muscle and bone in spinal cord injury (SCI). It is important to try to understand these changes, and the context in which they occur, because of their impact on the wellbeing of SC-injured individuals, and the urgent need for viable preventative therapies. Recent research provides new understanding of the effects of age and systemic factors on the response of bone to loading, of relevance to attempts to provide load therapy for bone in SCI. The rapidly growing dataset describing the biochemical crosstalk between bone and muscle, and the cell and molecular biology of myokines signalling to bone and osteokines regulating muscle metabolism and mass, is reviewed. The ways in which this crosstalk may be altered in SCI is summarised. Therapeutic approaches to the catabolic changes in muscle and bone in SCI require a holistic understanding of their unique mechanical and biochemical context.

Heightened TWEAK-NF-κB signaling and inflammation-associated fibrosis in paralyzed muscles of men with chronic spinal cord injury.

Individuals with long-standing spinal cord injury (SCI) often present with extreme muscle atrophy and impaired glucose metabolism at both the skeletal muscle and whole body level. Persistent inflammation and increased levels of proinflammatory cytokines in the skeletal muscle are potential contributors to dysregulation of glucose metabolism and atrophy; however, to date no study has assessed the effects of long-standing SCI on their expression or intracellular signaling in the paralyzed muscle. In the present study, we assessed the expression of genes (TNFαR, TNFα, IL-6R, IL-6, TWEAK, TWEAK R, atrogin-1, and MuRF1) and abundance of intracellular signaling proteins (TWEAK, TWEAK R, NF-κB, and p-p65/p-50/105) that are known to mediate inflammation and atrophy in skeletal muscle. In addition, based on the effects of muscle inflammation on promotion of skeletal muscle fibrosis, we assessed the degree of fibrosis between myofibers and fascicles in both groups. For further insight into the distribution and variability of muscle fiber size, we also analyzed the frequency distribution of SCI fiber size. Resting vastus lateralis (VL) muscle biopsy samples were taken from 11 men with long-standing SCI (≈22 yr) and compared with VL samples from 11 able-bodied men of similar age. Our results demonstrated that chronic SCI muscle has heightened TNFαR and TWEAK R gene expression and NF-κB signaling (higher TWEAK R and phospho-NF-κB p65) and fibrosis, along with substantial myofiber size heterogeneity, compared with able-bodied individuals. Our data suggest that the TWEAK/TWEAK R/NF-κB signaling pathway may be an important mediator of chronic inflammation and fibrotic adaptation in SCI muscle.

Skeletal muscle conditioning may be an effective rehabilitation intervention preceding functional electrical stimulation cycling.

In our recent effort, we introduced a submaximal index that utilized ventilatory efficiency relative to CO2 production (VE/CO2) to evaluate the cardiovascular effectiveness to functional electrical stimulation lower-extremity cycling (FES-LEC) in persons with spinal cord injury (SCI) (Gorgey and Lawrence, 2016). When compared to the resting state, we found that an acute bout of FES-LEC resulted in increased ventilation during exercise and a significant decrease of approximately 22% in the VE/CO2 ratio, suggesting that this ratio could be utilized to monitor the cardiovascular response during submaximal FES-LEC in the SCI population. The study demonstrated that a potential limitation to the FES-LEC application is a heavy reliance on carbohydrate storage as a main source of substrate utilization. Reliance on carbohydrate utilization, transformation to fast-twitch fibers following SCI and random muscle recruitment are likely to introduce rapid muscle fatigue during FES-LEC applications. This may limit oxygen uptake and outcomes regarding cardiovascular profile. In this perspective, we propose that skeletal muscle conditioning via surface neuromuscular electrical stimulation (NMES) may be an essential rehabilitation intervention to improve the outcomes of FES-LEC applications.

Low force contractions induce fatigue consistent with muscle mRNA expression in people with spinal cord injury.

Spinal cord injury (SCI) is associated with muscle atrophy, transformation of muscle fibers to a fast fatigable phenotype, metabolic inflexibility (diabetes), and neurogenic osteoporosis. Electrical stimulation of paralyzed muscle may mitigate muscle metabolic abnormalities after SCI, but there is a risk for a fracture to the osteoporotic skeletal system. The goal of this study was to determine if low force stimulation (3 Hz) causes fatigue of chronically paralyzed muscle consistent with selected muscle gene expression profiles. We tested 29 subjects, nine with a SCI and 20 without and SCI, during low force fatigue protocol. Three SCI and three non‐SCI subjects were muscle biopsied for gene and protein expression analysis. The fatigue index (FI) was 0.21 ± 0.27 and 0.91 ± 0.01 for the SCI and non‐SCI groups, respectively, supporting that the low force protocol physiologically fatigued the chronically paralyzed muscle. The post fatigue potentiation index (PI) for the SCI group was increased to 1.60 ± 0.06 (P <0.001), while the non‐SCI group was 1.26 ± 0.02 supporting that calcium handling was compromised with the low force stimulation. The mRNA expression from genes that regulate atrophy and fast properties (MSTN, ANKRD1, MYH8, and MYCBP2) was up regulated, while genes that regulate oxidative and slow muscle properties (MYL3, SDHB, PDK2, and RyR1) were repressed in the chronic SCI muscle. MSTN, ANKRD1, MYH8, MYCBP2 gene expression was also repressed 3 h after the low force stimulation protocol. Taken together, these findings support that a low force single twitch activation protocol induces paralyzed muscle fatigue and subsequent gene regulation. These findings suggest that training with a low force protocol may elicit skeletal muscle adaptations in people with SCI.

The validity of anthropometric leg muscle volume estimation across a wide spectrum: From able-bodied adults to individuals with a spinal cord injury

The assessment of muscle volume, and changes over time, have significant clinical and research-related implications. Methods to assess muscle volume vary from simple and inexpensive to complex and expensive. Therefore this study sought to examine the validity of muscle volume estimated simply by anthropometry compared with the more complex proton magnetic resonance imaging ((1)H-MRI) across a wide spectrum of individuals including those with a spinal cord injury (SCI), a group recognized to exhibit significant muscle atrophy. Accordingly, muscle volume of the thigh and lower leg of eight subjects with a SCI and eight able-bodied subjects (controls) was determined by anthropometry and (1)H-MRI. With either method, muscle volumes were significantly lower in the SCI compared with the controls (P < 0.05) and, using pooled data from both groups, anthropometric measurements of muscle volume were strongly correlated to the values assessed by (1)H-MRI in both the thigh (r(2) = 0.89; P < 0.05) and lower leg (r(2) = 0.98; P < 0.05). However, the anthropometric approach systematically overestimated muscle volume compared with (1)H-MRI in both the thigh (mean bias = 2407cm(3)) and the lower (mean bias = 170 cm(3)) leg. Thus with an appropriate correction for this systemic overestimation, muscle volume estimated from anthropometric measurements is a valid approach and provides acceptable accuracy across a spectrum of adults with normal muscle mass to a SCI and severe muscle atrophy. In practical terms this study provides the formulas that add validity to the already simple and inexpensive anthropometric approach to assess muscle volume in clinical and research settings.

Skeletal muscle signaling associated with impaired glucose tolerance in spinal cord-injured men and the effects of contractile activity

The mechanisms underlying poor glucose tolerance in persons with spinal cord injury (SCI), along with its improvement after several weeks of neuromuscular electrical stimulation-induced resistance exercise (NMES-RE) training, remain unclear, but presumably involve the affected skeletal musculature. We, therefore, investigated skeletal muscle signaling pathways associated with glucose transporter 4 (GLUT-4) translocation at rest and shortly after a single bout of NMES-RE in SCI (n = 12) vs. able-bodied (AB, n = 12) men. Subjects completed an oral glucose tolerance test during visit 1 and ≈90 NMES-RE isometric contractions of the quadriceps during visit 2. Muscle biopsies were collected before, and 10 and 60 min after, NMES-RE. We assessed transcript levels of GLUT-4 by quantitative PCR and protein levels of GLUT-4 and phosphorylated- and total AMP-activated protein kinase (AMPK)-α, CaMKII, Akt, and AS160 by immunoblotting. Impaired glucose tolerance in SCI was confirmed by higher (P < 0.05) plasma glucose concentrations than AB at all time points after glucose ingestion, despite equivalent insulin responses to the glucose load. GLUT-4 protein content was lower (P < 0.05) in SCI vs. AB at baseline. Main group effects revealed higher phosphorylation in SCI of AMPK-α, CaMKII, and Akt (P < 0.05), and Akt phosphorylation increased robustly (P < 0.05) following NMES-RE in SCI only. In SCI, low skeletal muscle GLUT-4 protein concentration may, in part, explain poor glucose tolerance, whereas heightened phosphorylation of relevant signaling proteins (AMPK-α, CaMKII) suggests a compensatory effort. Finally, it is encouraging to find (based on Akt) that SCI muscle remains both sensitive and responsive to mechanical loading (NMES-RE) even ≈22 yr after injury.

Not just quantity: Gluteus maximus muscle characteristics in able-bodied and SCI individuals – Implications for tissue viability

Study aimSome individuals with spinal cord injury (SCI) remain pressure ulcer (PU) free whilst others experience a recurring cycle of tissue breakdown. Detailed analysis of gluteal muscle characteristics may provide insights to local tissue viability variability. The study hypothesis was that SCI individuals have altered muscle composition compared to able-bodied (AB). MaterialsTen AB and ten SCI received a supine pelvic CT scan, with contrast. MethodsCross-sectional area (CSA) and overall muscle volume were derived using image analysis. Gluteal muscle tissue type was classified at the S2/S3 sacral vertebrae midpoint, the superior greater trochanters margin (GT) and the inferior ischial tuberosities margin (IT) using the linear transformation Hounsfield Unit scale. ResultsSCI gluteal CSA was less than for AB throughout the muscle, with the greatest relative atrophy at the IT (48%). Average AB gluteal volume was nearly double SCI. Eight SCI had over 20% infiltrative adipose tissue, three with over 50%. SCI gluteal CSA and intramuscular fat infiltration were significantly negatively correlated (p < 0.05). SCI IT axial slices showed less lean muscle and higher intramuscular fat infiltration than more proximally (p < 0.05). ConclusionSCI gluteal muscle characteristics were indicative of impaired tissue viability. SCI disuse muscle atrophy was anticipated; the analytic approach further indicated that intramuscular atrophy was not uniform. SCI muscle composition showed increased proportions of both low density muscle and adipose tissue. CT scan with contrast is effective for gluteal muscle characterization. This assessment technique may contribute to determination of personalized risk for PU development and other secondary complications.

The effects of n-3 fatty acids on bone markers in osteoporotic spinal cord injured patients

Some individuals with spinal cord injury (SCI) remain pressure ulcer (PU) free whilst others experience a recurring cycle of tissue breakdown. Detailed analysis of gluteal muscle characteristics may provide insights to local tissue viability variability. The study hypothesis was that SCI individuals have altered muscle composition compared to able-bodied (AB).Ten AB and ten SCI received a supine pelvic CT scan, with contrast.Cross-sectional area (CSA) and overall muscle volume were derived using image analysis. Gluteal muscle tissue type was classified at the S2/S3 sacral vertebrae midpoint, the superior greater trochanters margin (GT) and the inferior ischial tuberosities margin (IT) using the linear transformation Hounsfield Unit scale.SCI gluteal CSA was less than for AB throughout the muscle, with the greatest relative atrophy at the IT (48%). Average AB gluteal volume was nearly double SCI. Eight SCI had over 20% infiltrative adipose tissue, three with over 50%. SCI gluteal CSA and intramuscular fat infiltration were significantly negatively correlated (p < 0.05). SCI IT axial slices showed less lean muscle and higher intramuscular fat infiltration than more proximally (p < 0.05).SCI gluteal muscle characteristics were indicative of impaired tissue viability. SCI disuse muscle atrophy was anticipated; the analytic approach further indicated that intramuscular atrophy was not uniform. SCI muscle composition showed increased proportions of both low density muscle and adipose tissue. CT scan with contrast is effective for gluteal muscle characterization. This assessment technique may contribute to determination of personalized risk for PU development and other secondary complications.

Muscle perfusion of posterior trunk and lower-limb muscles at rest and during upper-limb exercise in spinal cord-injured and able-bodied individuals

Nonrandomized-controlled trial. To assess muscle perfusion at rest and during arm-cranking exercise (ACE) in upper and lower posterior trunk and vastus lateralis (VL) muscles in individuals with spinal cord injury (SCI) and controls (C). Exercise Physiology-Biochemistry Laboratory. Eight SCI with thoracic lesion and eight C received injections of radioactive tracer to trapezius (TRAP), latissimus dorsi (LAT) and VL. Radioactive counts were recorded with a γ-camera for 10 min at rest and during ACE (60% VO(2max) for 20 min). Time-count curves were generated and the isotope clearance rate, expressed as half-life time (T(1/2),min), was calculated to assess muscle perfusion. Resting T(1/2) was lower in TRAP and LAT vs VL (P<0.05) in SCI, however, there were no differences among muscles in C. Arm-cranking increased (P<0.001) the isotope clearance in TRAP and LAT in SCI and C, whereas no effect was found on T(1/2) in VL in both groups. T(1/2) was longer (P<0.05) in SCI vs C in VL at rest and during ACE, whereas there were no differences between groups in posterior trunk muscles. Resting muscle perfusion was reduced in the paralyzed limbs of SCI compared with C, whereas there was no evidence of impaired microcirculation in upper and lower back muscles in SCI. Although ACE did not induce a hyperemic response in VL, it increased hyperemia in upper and lower posterior trunk muscles in SCI, suggesting beneficial effects of this type of activity on muscle microvasculature in this region.

Effects of electrical stimulation-induced gluteal versus gluteal and hamstring muscles activation on sitting pressure distribution in persons with a spinal cord injury

Ten participants underwent two electrical stimulation (ES) protocols applied using a custom-made electrode garment with built-in electrodes. Interface pressure was measured using a force-sensitive area. In one protocol, both the gluteal and hamstring (g+h) muscles were activated, in the other gluteal (g) muscles only. To study and compare the effects of electrically induced activation of g+h muscles versus g muscles only on sitting pressure distribution in individuals with a spinal cord injury (SCI). Ischial tuberosities interface pressure (ITs pressure) and pressure gradient. In all participants, both protocols of g and g+h ES-induced activation caused a significant decrease in IT pressure. IT pressure after g+h muscles activation was reduced significantly by 34.5% compared with rest pressure, whereas a significant reduction of 10.2% after activation of g muscles only was found. Pressure gradient reduced significantly only after stimulation of g+h muscles (49.3%). g+h muscles activation showed a decrease in pressure relief (Δ IT) over time compared with g muscles only. Both protocols of surface ES-induced of g and g+h activation gave pressure relief from the ITs. Activation of both g+h muscles in SCI resulted in better IT pressure reduction in sitting individuals with a SCI than activation of g muscles only. ES might be a promising method in preventing pressure ulcers (PUs) on the ITs in people with SCI. Further research needs to show which pressure reduction is sufficient in preventing PUs.

Immature Heterotopic Ossification in the Iliacus Muscle in Spinal Cord Injury - A Case Report -

Heterotopic ossification (HO) is a frequent complication associated with spinal cord injury and can lead to significant problems during rehabilitation. Surgical resection of HO could be applied to patients who do not respond to conservative treatment. To reduce the risk of recurrence after the operation, radiation therapy and NSAID or bisphosphonate administration may be utilized. We report the case of a 48-year-old male with a T3-sparing spinal cord injury who underwent successful treatment of immature HO in the iliacus muscle with a combination of surgical resection, radiation therapy, and NSAID administration.

Cellular-scale transport in deformed skeletal muscle following spinal cord injury

Deep tissue injury (DTI) is a severe pressure ulcer initiating in weight-bearing skeletal muscles. Being common in spinal cord injury (SCI) patients, DTI is associated with mechanical cell damage and ischaemia. Muscle microanatomy in SCI patients is characterised by reduced myofibre sizes and smaller, fewer capillaries. We hypothesise that these changes influence mass transport in SCI muscles, making DTI more probable. Using multiphysics models of microscopic cross-sections through normal and SCI muscles, we studied effects of the following factors on transport of glucose and myoglobin (potential biomarker for early DTI detection): (i) abnormal SCI muscle microanatomy, (ii) large tissue deformations and (iii) ischaemia. We found that the build-up of concentrations of glucose and myoglobin is slower for SCI muscles, which could be explained by the pathological SCI microanatomy. These findings overall suggest that microanatomical changes in muscles post-SCI play an important role in the vulnerability of the SCI patients to DTI.

Comprehensive Joint Feedback Control for Standing by Functional Neuromuscular Stimulation—A Simulation Study

Previous investigations of feedback control of standing after spinal cord injury (SCI) using functional neuromuscular stimulation (FNS) have primarily targeted individual joints. This study assesses the potential efficacy of comprehensive (trunk, hips, knees, and ankles) joint feedback control against postural disturbances using a bipedal, 3-D computer model of SCI stance. Proportional-derivative feedback drove an artificial neural network trained to produce muscle excitation patterns consistent with maximal joint stiffness values achievable about neutral stance given typical SCI muscle properties. Feedback gains were optimized to minimize upper extremity (UE) loading required to stabilize against disturbances. Compared to the baseline case of maximum constant muscle excitations used clinically, the controller reduced UE loading by 55% in resisting external force perturbations and by 84% during simulated one-arm functional tasks. Performance was most sensitive to inaccurate measurements of ankle plantar/dorsiflexion position and hip ab/adduction velocity feedback. In conclusion, comprehensive joint feedback demonstrates potential to markedly improve FNS standing function. However, alternative control structures capable of effective performance with fewer sensor-based feedback parameters may better facilitate clinical usage.

Cell-level temperature distributions in skeletal muscle post spinal cord injury as related to deep tissue injury

Deep tissue injury (DTI) is a severe pressure ulcer, which initiates in skeletal muscle tissue under intact skin. Patients with spinal cord injury (SCI) are especially vulnerable to DTI, due to their impaired motosensory capacities. The underlying mechanisms that lead to DTI are, however, still poorly understood. This study focuses on cell-level temperature distributions in muscles of patients with SCI, which typically contain thinner muscle fibers and fewer capillaries. It has been shown previously by our group that ischemic muscles of rat models of DTI cool down mildly and locally, which is very likely to slow the diffusivity of metabolites in the ischemic regions. However, it is unclear how these temperature decreases affect diffusivity at the scale of individual muscle cells in the microanatomy of SCI patients. We hypothesize that a 2 degrees C drop in the temperature of inflowing capillary blood, as shown in our animal studies, has a substantial effect on lowering the diffusivity of metabolites in skeletal muscle, but the pathological microanatomy in the chronic phase of SCI is less dominant in affecting the local temperatures in and around muscle cells. In order to test this hypothesis, two-dimensional finite element (FE) models of cross sections through the microanatomy of muscle tissue were developed using COMSOL Multiphysics software for normal and SCI muscles. The models included muscle cells, extracellular matrix (ECM), and capillaries, each with its own geometrical, thermal, and heat production properties. The SCI model configuration specifically included reduced cross section of myofibrils in favor of more ECM, less capillaries, and decreased blood inflow rate. After a 20-s heat transfer simulation, it was found that temperatures around the cells of the SCI muscle were approximately 2 degrees C lower than that in the normal muscle, that is, heat production from the muscle cell metabolism did not compensate for the lower inflowing blood temperature in the SCI model. We conclude that the temperature and rate of inflowing capillary blood are the dominant factors determining the localized temperatures in the microarchitecture of an ischemic SCI muscle tissue. The altered SCI microanatomy was shown to be less influential. Taken together with the Stokes-Einstein theory, our results indicate that diffusivity of metabolites would be approximately 50% less around the cells of SCI muscle due to local cooling, which is yet another factor compromising tissue viability in the patients with SCI.

Enhancement of Operational Efficiencies for People With High Cervical Spinal Cord Injuries Using a Flexible Integrated Pointing Device Apparatus

Chen C-L, Chen H-C, Cheng P-T, Chen C-Y, Chen H-C, Chou S-W. Enhancement of operational efficiencies for people with high cervical spinal cord injuries using a flexible integrated pointing device apparatus. Objective To investigate the effectiveness of a universal integrated pointing device apparatus (IPDA), which can integrate numerous commercial pointing devices and can be controlled by various combinations of available movements, for people with cervical spinal cord injury (SCI) who cannot operate standard computer pointing devices. Design An exploratory quasi-experimental design. All subjects were required to perform specific mouse-operating (continuous-clicking, target-acquisition, drag-and-drop) tasks. People with SCI received clinical assessments and were classified into 2 groups based on pointing device used: group A, who used standard mouse devices, and group B (IPDA combinations), who were unable to use standard mouse devices. The measures of group A and group B were compared. Setting Rehabilitation science center of a medical institution. Participants Thirty-seven people with high cervical SCI and 30 able-bodied subjects. Intervention The IPDA. Main Outcome Measures The efficiency of the people with SCI in each mouse-operation task was expressed as a percentage of that for able-bodied subjects (%NL). Results Group B displayed similar operational efficiency in performing the drag-and-drop tasks (≈30% NL) to group A, although they exhibited worse efficiency than group A in performing the other tasks ( P<.05). Operational efficiencies of all tasks had negative relationships with age by using linear regression analysis (adjusted r 2>.36, P<.001). The use of pointing devices was associated with American Spinal Injury Association Impairment Scale ( P<.001), completeness ( P<.001), and muscle strength ( P<.01), particularly finger flexor muscle strength, but not with neurologic level or muscle tone. Conclusions The IPDA could help most people with high cervical SCI who could not use commercial mouse devices to achieve acceptable operational efficiencies. Pointing devices were assigned based on the underlying SCI severity and muscle strength, particularly finger flexor muscle strength.

Reflex reciprocal facilitation of antagonist muscles in spinal cord injury.

Electromyographic study in complete and incomplete spinal cord injury (SCI). To examine the changes in the pattern of reciprocal inhibition between agonist and antagonist muscles in SCI. Sensory Motor Performance Program, Rehabilitation Institute of Chicago, IL, USA. Tendon taps were delivered manually with an instrumented hammer to the tendons of the tibialis anterior and soleus muscle in positions of full-ankle dorsiflexion and plantarflexion in eight subjects with complete SCI and eight subjects with incomplete SCI. Electromyographic activity (EMG) was recorded from ankle dorsiflexor and plantarflexor muscles. Tapping force was also recorded by a force sensor mounted to the tendon hammer, indicating the stimulus onset. Measures of reflex EMG magnitude and reflex latency were obtained for both agonist and antagonist muscles. The ratio of antagonist to agonist EMG was computed based on normalized EMG. Substantial reflex responses occurred in both the stretched muscle and in its antagonist. The reflex in antagonist, which we term 'reciprocal facilitation (RF)', was most evident in subjects with incomplete SCI. The magnitude of RF was consistently greater than reflex responses in agonist muscles under all test conditions. The latency of the RF was comparable to that of monosynaptic reflex response. Following SCI, reciprocal organization of segmental reflexes at the ankle is often partially or completely suppressed, allowing reflex activation in antagonist muscles to be manifested. Possible mechanisms underlying these changes in neural organization are discussed. This study was supported by Spinal Cord Research Foundation, the Paralyzed Veterans of America.