Vibration training after chronic spinal cord injury: Evidence for persistent segmental plasticity.

H-reflex paired-pulse depression is gradually lost within the first year post-SCI, a process believed to reflect reorganization of segmental interneurons after the loss of normal descending (cortical) inhibition. This reorganization co-varies in time with the development of involuntary spasms and spasticity. The purpose of this study is to determine whether long-term vibration training may initiate the return of H-reflex paired-pulse depression in individuals with chronic, complete SCI. Five men with SCI received twice-weekly vibration training (30Hz, 0.6g) to one lower limb while seated in a wheelchair. The contra-lateral limb served as a within-subject control. Paired-pulse H-reflexes were obtained before, during, and after a session of vibration. Untrained limb H-reflex depression values were comparable to chronic SCI values from previous reports. In contrast, the trained limbs of all 5 participants showed depression values that were within the range of previously-reported Acute SCI and Non-SCI H-reflex depression. The average difference between limbs was 34.98% (p=0.016). This evidence for the return of H-reflex depression suggests that even for people with long-standing SCI, plasticity persists in segmental reflex pathways. The spinal networks involved with the clinical manifestation of spasticity may thus retain adaptive plasticity after long-term SCI. The results of this study indicate that vibration training may hold promise as an anti-spasticity rehabilitation intervention.

Effect of Surgery on Gait and Sensory Motor Performance in Patients With Cervical Spondylotic Myelopathy.

BACKGROUND: Cervical spondylotic myelopathy (CSM) is a common disease of aging that leads to gait instability resulting from loss of leg sensory and motor functions. The results of surgical intervention have been studied using a variety of methods, but no test has been reported that objectively measures integrative leg motor sensory functions in CSM patients. OBJECTIVE: To determine the feasibility of using a novel single leg squat (SLS) test to measure integrative motor sensory functions in patients with CSM before and after surgery. METHODS: Fifteen patients with CSM were enrolled in this prospective study. Clinical data and scores from standard outcomes questionnaires were obtained before and after surgery. Patients also participated in experimental test protocols consisting of standard kinematic gait testing, the Purdue pegboard test, and the novel SLS test. RESULTS: The SLS test protocol was well tolerated by CSM patients and generated objective performance data over short test periods. In patients who participated in postoperative testing, the group measures of mean SLS errors decreased following surgery. Gait velocity measures followed a similar pattern of group improvement postoperatively. Practical barriers to implementing this extensive battery of tests resulted in subject attrition over time. Compared with kinematic gait testing, the SLS protocol required less space and could be effectively implemented more efficiently. CONCLUSIONS: The SLS test provides a practical means of obtaining objective measures of leg motor sensory functions in patients with CSM. Additional testing with a larger cohort of patients is required to use SLS data to rigorously examine group treatment effects. ABBREVIATIONS: BW, body weightCSM, cervical spondylotic myelopathymJOA, modified Japanese Orthopedic AssociationSLS, single leg squat.

Distinct Skeletal Muscle Gene Regulation from Active Contraction, Passive Vibration, and Whole Body Heat Stress in Humans.

UNLABELLED: Skeletal muscle exercise regulates several important metabolic genes in humans. We know little about the effects of environmental stress (heat) and mechanical stress (vibration) on skeletal muscle. Passive mechanical stress or systemic heat stress are often used in combination with many active exercise programs. We designed a method to deliver a vibration stress and systemic heat stress to compare the effects with active skeletal muscle contraction. PURPOSE: The purpose of this study is to examine whether active mechanical stress (muscle contraction), passive mechanical stress (vibration), or systemic whole body heat stress regulates key gene signatures associated with muscle metabolism, hypertrophy/atrophy, and inflammation/repair. METHODS: Eleven subjects, six able-bodied and five with chronic spinal cord injury (SCI) participated in the study. The six able-bodied subjects sat in a heat stress chamber for 30 minutes. Five subjects with SCI received a single dose of limb-segment vibration or a dose of repetitive electrically induced muscle contractions. Three hours after the completion of each stress, we performed a muscle biopsy (vastus lateralis or soleus) to analyze mRNA gene expression. RESULTS: We discovered repetitive active muscle contractions up regulated metabolic transcription factors NR4A3 (12.45 fold), PGC-1α (5.46 fold), and ABRA (5.98 fold); and repressed MSTN (0.56 fold). Heat stress repressed PGC-1α (0.74 fold change; p < 0.05); while vibration induced FOXK2 (2.36 fold change; p < 0.05). Vibration similarly caused a down regulation of MSTN (0.74 fold change; p < 0.05), but to a lesser extent than active muscle contraction. Vibration induced FOXK2 (p < 0.05) while heat stress repressed PGC-1α (0.74 fold) and ANKRD1 genes (0.51 fold; p < 0.05). CONCLUSION: These findings support a distinct gene regulation in response to heat stress, vibration, and muscle contractions. Understanding these responses may assist in developing regenerative rehabilitation interventions to improve muscle cell development, growth, and repair.

Effects of brain derived neurotrophic factor Val66Met polymorphism in patients with cervical spondylotic myelopathy.

Cervical spondylotic myelopathy (CSM) is the leading cause of spinal cord related disability in the elderly. It results from degenerative narrowing of the spinal canal, which causes spinal cord compression. This leads to gait instability, loss of dexterity, weakness, numbness and urinary dysfunction. There has been indirect data that implicates a genetic component to CSM. Such a finding may contribute to the variety in presentation and outcome in this patient population. The Val66Met polymorphism, a mutation in the brain derived neurotrophic factor (BDNF) gene, has been implicated in a number of brain and psychological conditions, and here we investigate its role in CSM. Ten subjects diagnosed with CSM were enrolled in this prospective study. Baseline clinical evaluation using the modified Japanese Orthopaedic Association (mJOA) scale, Nurick and 36-Item Short Form Health Survey (SF-36) were collected. Each subject underwent objective testing with gait kinematics, as well as hand functioning using the Purdue Peg Board. Blood samples were analyzed for the BDNF Val66Met mutation. The prevalence of the Val66Met mutation in this study was 60% amongst CSM patients compared to 32% in the general population. Individuals with abnormal Met allele had worse baseline mJOA and Nurick scores. Moreover, baseline gait kinematics and hand functioning testing were worse compared to their wild type counterpart. BDNF Val66Met mutation has a higher prevalence in CSM compared to the general population. Those with BDNF mutation have a worse clinical presentation compared to the wild type counterpart. These findings suggest implication of the BDNF mutation in the development and severity of CSM.

Potential regenerative rehabilitation technology: implications of mechanical stimuli to tissue health.

BACKGROUND: Mechanical loads induced through muscle contraction, vibration, or compressive forces are thought to modulate tissue plasticity. With the emergence of regenerative medicine, there is a need to understand the optimal mechanical environment (vibration, load, or muscle force) that promotes cellular health. To our knowledge no mechanical system has been proposed to deliver these isolated mechanical stimuli in human tissue. We present the design, performance, and utilization of a new technology that may be used to study localized mechanical stimuli on human tissues. A servo-controlled vibration and limb loading system were developed and integrated into a single instrument to deliver vibration, compression, or muscle contractile loads to a single limb (tibia) in humans. The accuracy, repeatability, transmissibility, and safety of the mechanical delivery system were evaluated on eight individuals with spinal cord injury (SCI). FINDINGS: The limb loading system was linear, repeatable, and accurate to less than 5, 1, and 1 percent of full scale, respectively, and transmissibility was excellent. The between session tests on individuals with spinal cord injury (SCI) showed high intra-class correlations (>0.9). CONCLUSIONS: All tests supported that therapeutic loads can be delivered to a lower limb (tibia) in a safe, accurate, and measureable manner. Future collaborations between engineers and cellular physiologists will be important as research programs strive to determine the optimal mechanical environment for developing cells and tissues in humans.

Variability of motor cortical excitability using a novel mapping procedure.

The purpose of this study was to assess the reliability of a novel TMS motor cortex mapping procedure. The procedure was designed to take less time and be more clinically useful by delivering fewer MEPS over fewer skull locations. Resting motor evoked potentials (MEPs) were recorded from the first dorsal interosseus muscle of 6 individuals over a fixed 15-point grid. Mean MEP amplitudes, map center of gravity (CoG), and stimulus-response characteristics were assessed before and after a 30-min rest session. As a novel feature, subregions of the map were analyzed for regions of highest test-retest reliability for use as a global measure of cortical excitability. Mean MEP amplitudes between sessions were highly reliable (ICC=0.90-0.92). Reproducibility of MEPs was highest along an axis approximately 45° to the nasion-inion. Stimulus-response MEP amplitudes showed moderate to high reliability (ICC 0.54-0.95). Mean CoG shift between sessions was 2.79±1.2mm. This mapping procedure is reliable and allows efficient assessment of motor cortex excitability.

A biomechanical analysis of exercise in standing, supine, and seated positions: Implications for individuals with spinal cord injury.

CONTEXT/OBJECTIVE: The distal femur is the primary fracture site in patients with osteoporosis after spinal cord injury (SCI). OBJECTIVE: To mathematically compare the compression and shear forces at the distal femur during quadriceps stimulation in the standing, supine, and seated positions. A force analysis across these positions may be a consideration for people with SCI during neuromuscular electrical stimulation of the quadriceps. DESIGN: A biomechanical model. SETTING: Research laboratory. OUTCOME MEASURES: Compression and shear forces from the standing, supine, and seated biomechanical models at the distal femur during constant loads generated by the quadriceps muscles. RESULTS: The standing model estimated the highest compressive force at 240% body weight and the lowest shear force of 24% body weight at the distal femur compared with the supine and seated models. The supine model yielded a compressive force of 191% body weight with a shear force of 62% body weight at the distal femur. The seated model yielded the lowest compressive force of 139% body weight and the highest shear force of 215% body weight. CONCLUSIONS: When inducing a range of forces in the quadriceps muscles, the seated position yields the highest shear forces and lowest compressive forces when compared with the supine and standing positions. Standing with isometric contractions generates the highest compressive loads and lowest shear forces. Early active resistive standing may provide the most effective means to prevent bone loss after SCI.

Limb segment vibration modulates spinal reflex excitability and muscle mRNA expression after spinal cord injury.

OBJECTIVE: We investigated the effect of various doses of vertical oscillation (vibration) on soleus H-reflex amplitude and post-activation depression in individuals with and without SCI. We also explored the acute effect of short-term limb vibration on skeletal muscle mRNA expression of genes associated with spinal plasticity. METHODS: Six healthy adults and five chronic complete SCI subjects received vibratory stimulation of their tibia over three different gravitational accelerations (0.3g, 0.6g, and 1.2g) at a fixed frequency (30Hz). Soleus H-reflexes were measured before, during, and after vibration. Two additional chronic complete SCI subjects had soleus muscle biopsies 3h following a single bout of vibration. RESULTS: H-reflex amplitude was depressed over 83% in both groups during vibration. This vibratory-induced inhibition lasted over 2min in the control group, but not in the SCI group. Post-activation depression was modulated during the long-lasting vibratory inhibition. A single bout of mechanical oscillation altered mRNA expression from selected genes associated with synaptic plasticity. CONCLUSIONS: Vibration of the lower leg inhibits the H-reflex amplitude, influences post-activation depression, and alters skeletal muscle mRNA expression of genes associated with synaptic plasticity. SIGNIFICANCE: Limb segment vibration may offer a long term method to reduce spinal reflex excitability after SCI.

Enhancing muscle force and femur compressive loads via feedback-controlled stimulation of paralyzed quadriceps in humans.

OBJECTIVE: To compare paralyzed quadriceps force properties and femur compressive loads in an upright functional task during conventional constant-frequency stimulation and force feedback-modulated stimulation. DESIGN: Crossover trial. SETTING: Research laboratory. PARTICIPANTS: Subjects (N=13; 12 men, 1 woman) with motor-complete spinal cord injury. INTERVENTIONS: Subjects performed 2 bouts of 60 isometric quadriceps contractions while supported in a standing frame. On separate days, subjects received constant-frequency stimulation at 20Hz (CONST) or frequency-modulated stimulation triggered by a change in force (FDBCK). During FDBCK, a computer algorithm responded to each 10% reduction in force with a 20% increase in stimulation frequency. MAIN OUTCOME MEASURES: A biomechanical model was used to derive compressive loads on the femur, with a target starting dose of load equal to 1.5 times body weight. RESULTS: Peak quadriceps force and fatigue index were higher for FDBCK than CONST (P<.05). Within-train force decline was greater during FDBCK bouts, but mean force remained above CONST values (P<.05). As fatigue developed during repetitive stimulation, FDBCK was superior to CONST for maintenance of femur compressive loads (P<.05). CONCLUSIONS: Feedback-modulated stimulation in electrically activated stance is a viable method to maximize the physiologic performance of paralyzed quadriceps muscle. Compared with CONST, FDBCK yielded compressive loads that were closer to a targeted dose of stress with known osteogenic potential. Optimization of muscle force with FDBCK may be a useful tactic for future training-based antiosteoporosis protocols.