The Use of Skeletal Muscle to Amplify Action Potentials in Transected Peripheral Nerves

Upper limb amputees suffer with problems associated with control and attachment of prostheses. Skin-surface electrodes placed over the stump, which detect myoelectric signals, are traditionally used to control hand movements. However, this method is unintuitive, the electrodes lift-off, and signal selectivity can be an issue. One solution to these limitations is to implant electrodes directly on muscles. Another approach is to implant electrodes directly into the nerves that innervate the muscles. A significant challenge with both solutions is the reliable transmission of biosignals across the skin barrier. In this thesis, I investigated the use of implantable muscle electrodes in an ovine model using myoelectrodes in combination with a bone-anchor, acting as a conduit for signal transmission. High-quality readings were obtained which were significantly better than skin-surface electrode readings. I further investigated the effect of electrode configurations to achieve the best signal quality. For direct recording from nerves, I tested the effect of adsorbed endoneural basement membrane proteins on nerve regeneration in vivo using microchannel neural interfaces implanted in rat sciatic nerves. Muscle and nerve signal recordings were obtained and improvements in sciatic nerve function were observed. Direct skeletal fixation of a prosthesis to the amputation stump using a bone-anchor has been proposed as a solution to skin problems associated with traditional socket-type prostheses. However, there remains a concern about the risk of infection between the implant and skin. Achieving a durable seal at this interface is therefore crucial, which formed the final part of the thesis. Bone-anchors were optimised for surface pore size and coatings to facilitate binding of human dermal fibroblasts to optimise skin-implant seal in an ovine model. Implants silanised with Arginine-Glycine-Aspartic Acid experienced significantly increased dermal tissue infiltration. This approach may therefore improve the soft tissue seal, and thus success of bone-anchored implants. By addressing both the way prostheses are attached to the amputation stump, by way of direct skeletal fixation, as well as providing high fidelity biosignals for high-level intuitive prosthetic control, I aim to further the field of limb loss rehabilitation

Assessment of Intrinsic Hand Neuromuscular Physiology

Alterations to the peripheral nervous system and neuromuscular physiology may impact hand function in a typical or clinical population, such as individuals with ulnar neuropathy. The mechanisms that influence these positive and negative changes are still not well understood. The three studies within my thesis aim to validate the reliability of decomposition-based quantitative electromyography (DQEMG) measurements and explore the changes in intrinsic hand neuromuscular physiology in a typical aging population and individuals recovering from a surgical intervention for severe ulnar neuropathy. The purpose of the first study was to determine the test-retest reliability of near-fibre (NF) jiggle, a measure of motor unit stability. I found that NF jiggle had good measurement reliability with low error, especially when contrasted with traditional jiggle. The context of this reliability was specific to the intrinsic hand muscles: first dorsal interosseus (FDI), abductor digiti minimi (ADM), and fourth dorsal interosseous (4DI). The purpose of the second study was to compare the intrinsic hand neuromuscular physiology of a typical aging population using multivariate analyses. I determined that with aging, there are decreases in motor unit number estimations (MUNE) and motor unit stability (NF jiggle) with increases to motor unit potential (MUP) area in the intrinsic hand muscles. Using a multivariate approach allowed for age-related differences and the relationship between the variables to be further elucidated. The purpose of the third study was to describe the responses, functional outcome, and motor unit physiology of three participants following an ulnar nerve transfer surgery to treat severe ulnar neuropathy and the rehabilitation that followed. I determined that functional outcomes were associated with improvements to neuromuscular physiology and may be influenced by rehabilitation adherence. Also, factors such as comorbidities, psychosocial barriers and delay in treatment may affect functional outcomes and rehabilitation adherence. Overall, the progression of quantitative EMG measurements and exploring mechanisms of neuromuscular changes in aging and clinical populations provide foundational knowledge that may impact rehabilitation and treatment approaches. I hope that my thesis may provide new avenues of assessment, treatment, and prognosis for persons with pathologies that influence hand function and neuromuscular physiology

Brachial Plexus Injury

In this book, specialists from different countries and continents share their knowledge and experience in brachial plexus surgery. It discusses the different types of brachial plexus injury and advances in surgical treatments

CIR-Myo News: Abstracts of the 2015 Spring Padua Muscle Days

Not available

Analysis of Tissue Sparing and Circuit Regeneration in Spinal Cord Injuries Treated with Biomaterials and Gene Therapy

Each year, the U.S. sees nearly 17,700 new cases of spinal cord injuries (SCIs). Despite intense rehabilitation, patients with SCIs most often suffer lifelong physical consequences and substantial increases in medical expenses per individual. While immobilization and surgery can be used for immediate stabilization of the injury, no clinical methods exist to address the subsequent inflammation and lack of tissue regeneration that further contribute to the motor and sensory deficits seen after an SCI. This dissertation aimed to understand how biomaterials and gene therapy treatment affect SCIs. In a mouse SCI model, where a left C5 hemisection results in loss of function of the left arm, a poly(lactide-co-glycolide) (PLG) scaffold or “bridge” can be implanted in place of the resected tissues. The bridge can be loaded with lentivirus for local delivery of gene therapy that can aid in control of the post-SCI microenvironment. Using lentiviral interleukin-10 (IL10), we found that IL10 animals significantly outperform animals that received a control lentivirus on a ladder beam test at 2- and 12- weeks post-injury (wpi). Closer examination of components of the forelimb motor circuitry suggest IL10 animals had increased sparing of lower motor neurons and neuromuscular junctions. Electrophysiological studies at 2 wpi showed that control injured animals had electromyogram recordings that were significantly dampened when compared to IL10 and control uninjured animals, thereby confirming that the motor circuitry remained more intact with IL10 treatment. These results, which were consistent in both male and female mice, are the first to show that IL10 spares motor circuitry directly responsible for enhanced muscle function. We then tested a combination therapy of lentiviral IL10 and brain-derived neurotrophic factor (BDNF), followed by examination of tissue sparing and regeneration. At 2 wpi, histological and electrophysiological analyses show that the tissue sparing effects of IL10 alone are only slightly enhanced by the addition of BDNF. By 12 wpi, most innervation differences among the treatment conditions disappeared, though electrophysiological examination suggests that IL10 may prevent some of the injury-associated shifts in muscle composition that result in increased fatigability in control injured animals. Within the spinal cord, we found that IL10 alone and IL10+BDNF cause a similar increase in axon growth across the injury site. 3D imaging using Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging / Immunostaining / in situ-hybridization-compatible Tissue Hydrogel (CLARITY) shows these axons do completely traverse the injury site, while electrophysiological studies suggest these axons are able to carry action potentials. These results are the first to show that regenerated axons can be electrophysiologically active. Taken together, these studies suggest early immunomodulation can have long-lasting benefits through tissue sparing, and that regenerated axons have the potential to transduce signals across an injury site. These findings provide novel insights into how the pathophysiology following an SCI can be altered using biomaterials and gene therapy. Future studies will involve identifying the synaptic targets of regenerated axons and determining how the formation of new circuits can influence motor function.PHDNeuroscienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/163028/1/chenjess_1.pd

Muscle Activity in Upper Extremity Amputees

Purpose – Three interdependent studies designed as preliminary investigations of phantom and prosthetic limb control in upper extremity amputees. The purpose was to (1) compare muscle activation patterns of the phantom limb to anatomically expected patterns (2) compare muscle activation patterns of the phantom limb and those used to control a prosthesis (3) compare the use of upper arm muscle activity in phantom limb movements between users of different types of prosthetic devices. These studies aimed to expand the understanding of the role of the peripheral nervous system in movements of phantom and prosthetic limbs. Methods – Fifteen participants with varying levels of upper extremity amputations participated. Kinesiologic EMG (surface/fine wire) was utilized to examine residual limb muscle activation patterns during movements of the phantom and prosthesis. A series of phantom movements based on level of amputation were executed. After completing phantom limb movements participants donned their prosthesis and completed movements of the device. Muscles were considered active when the threshold of activity exceeded two standard deviations above rest trial. Visual analysis of EMG activity and goodness of fit Pearson Chi-Square tests were used to examine frequency occurrences in muscle activation patterns. Results –The majority of muscle activation patterns for the completion of phantom limb movements, regardless of the level of amputation, varied from anatomically expected muscle activation patterns. The majority of participants also used different muscle activation patterns to control similar movements of the phantom limb and prosthetic device. Finally, muscle activation patterns to control the movement of a phantom hand were different based on the type of device participants used, with body-powered prosthetic users activating muscles of the upper arm more frequently than myoelectric prosthetic users. Significance – This dissertation was a preliminary study into novel theories regarding phantom and prosthetic control. Results emphasize a dire need for future research to explore the injury response of the PNS, how this impacts phantom limb experiences, how these changes impact or is impacted by the CNS, and how to utilize the body’s natural response to injury to enhance control and function of prosthetic devices

Therapy Options for Winged Scapula Patients: A Literature Review

Winged scapula is a condition characterized by lateral or medial protrusion of the scapula caused by nerve damage leading to muscular paralysis. The purpose of this systematic review of literature is to evaluate the current research literature related to the effectiveness of therapy options for winged scapula. Eleven peer reviewed English language research articles published from 1998 to present were included for evaluation. Study results revealed positive therapeutic outcomes for physical therapy and scapular bracing. Results also showed positive outcomes for the use of transcutaneous electrical nerve stimulation and acupuncture for the treatment of nerve related conditions similar to winged scapula. Additional research is needed to evaluate the effectiveness of transcutaneous electrical nerve stimulation and acupuncture for winged scapula patients specifically