Impacts of Diabetic Neuropathy on the Human Neuromuscular System

Diabetes mellitus (DM) imparts vascular and metabolic stressors that cause damage and dysfunction to the human nervous system. The disorder associated with this dysfunction is termed diabetic polyneuropathy (DPN). Although DPN has been associated with muscle weakness and atrophy, the extent of its impacts on the neuromuscular system is not well understood. The five studies presented in my thesis investigated how DPN affects the neuromuscular system in humans, from the motor neuron to skeletal muscle contractile properties, using a combination of electromyography (EMG), dynamometry and magnetic resonance imaging (MRI) techniques. The purpose of Studies 1 and 2 was to determine whether the neurogenic loss of motor units underlies the muscle weakness and atrophy associated with DPN, and to investigate how these changes may differ in an upper and lower limb muscle. I determined DPN patients feature reduced motor unit estimates (MUNEs) compared to controls, and progression of motor unit loss in DPN may follow a length-dependent pattern. The purpose of Study 3 was to assess the stability of neuromuscular transmission in patients with DPN compared with healthy controls, using a novel set of electrodiagnostic parameters obtained via quantitative EMG. I determined DPN patients have less stable neuromuscular transmission, and the feature intermittent conduction failure at a relatively low contraction intensity. The purpose of Study 4 was to investigate skeletal muscle contractile properties and morphology in DPN patients associated with the severity of muscle denervation. I determined DPN patients possess slowed muscle, with greater proportional amounts of non-contractile muscle tissue compared to controls. The purpose of Study 5 was to explore the fatigability of DPN patients during a sustained, maximal voluntary contraction (MVC). I determined DPN patients have less endurance than controls, and their increased fatigability may be associated with neuromuscular transmission failure. Overall these foundational explorations greatly expand our knowledge of how DPN can impact the neuromuscular system in humans. Furthermore, the studies contained within my thesis may help direct further useful studies and strategies to understand, and direct clinical support in those with DPN

Applications of EMG in Clinical and Sports Medicine

This second of two volumes on EMG (Electromyography) covers a wide range of clinical applications, as a complement to the methods discussed in volume 1. Topics range from gait and vibration analysis, through posture and falls prevention, to biofeedback in the treatment of neurologic swallowing impairment. The volume includes sections on back care, sports and performance medicine, gynecology/urology and orofacial function. Authors describe the procedures for their experimental studies with detailed and clear illustrations and references to the literature. The limitations of SEMG measures and methods for careful analysis are discussed. This broad compilation of articles discussing the use of EMG in both clinical and research applications demonstrates the utility of the method as a tool in a wide variety of disciplines and clinical fields

Coupling Robot-aided assessment and surface electromyography to evaluate wrist and forearm muscles activity, muscle fatigue and its effect on proprioception

Sensorimotor functions and an intact neural control of muscles are essential for the effective execution of movements during daily living tasks. However, despite the ability of human sensorimotor system to cope with a great diversity of internal and external demands and constraints, these mechanisms can be altered as a consequence of neurological disorders, injuries or just due to excessive effort leading to muscle fatigue. A precise assessment of both motor and sensory impairment is thus needed in order to provide useful cues to monitor the progression of the disease in pathological populations or to prevent injuries in case of workers. In particular, considering muscle fatigue, an objective assessment of its manifestation may be crucial when dealing with subjects with neuromuscular disorders for understanding how specific disease features evolve over time or for testing the efficacy of a potential therapeutic strategy. Indeed, muscle fatigue accounts for a significant portion of the disease burden in populations with neuromuscular diseases but, despite its importance, a standardized, reliable and objective method for fatigue measurement is lacking in clinical practice. The work presented in this thesis investigates a practical solution through the use of a robotic task and parameters extracted by surface electromyography signals. Moreover, a similar approach that combines robot-mediated proprioception test and muscle fatigue assessment has been developed and used in this thesis to objectively investigate the influence of muscle fatigue on position sense. Finally, the effect of posture on muscle activity, from a perspective of injuries prevention, has been examined. Data on adults and children have been collected and quantitative and objective information about muscle activity, muscle fatigue and joint sensitivity were obtained gaining useful insight both in the clinical context and in the prevention of workplace injuries. A novel method to assess muscle fatigue has been proposed together with the definition of an easy readable indicator that can help clinicians in the assessment of the patient. As for the impact of fatigue on the sensorimotor system, results obtained showed a decrease in wrist proprioceptive acuity which led also to a decline in the performance of a simple tracing task. Regarding the adoption of different muscle strategies depending on postures, results showed that muscle activity of forearm muscles was overall similar regardless from the postures

Evaluation of the Utility of Decomposition-Enhanced Spike-Triggered Averaging Motor Unit Number Estimation as an Outcome Measure for the Study of Amyotrophic Lateral Sclerosis

OBJECTIVES: The objectives of this thesis were to review the use of outcome measures systematically across amyotrophic lateral sclerosis (ALS) clinical trials, and evaluate the utility of decomposition-enhanced spike-triggered averaging (DE-STA) motor unit number estimation (MUNE) as an outcome measure, with a particular focus on its application to the upper trapezius (UT). METHODS: First, a systematic review quantified the frequency of use of outcome measures in ALS randomized controlled trials (Chapter 2). Next, the intra- and inter-rater reliability of DE-STA MUNE was evaluated in the UT of control subjects (Chapter 3), followed by the intra-rater reliability of the technique in the UT and biceps brachii of subjects with ALS (Chapter 4). To assess validity, the results of the technique in the UT were compared between subjects with ALS and control subjects (Chapter 4). The sensitivity to change of DE-STA MUNE in the UT was compared with that of various clinical outcome measures in a longitudinal study of subjects with ALS (Chapter 5). Finally, the influence of needle electrode depth on the results of the technique in the UT was evaluated in control subjects (Chapter 6). RESULTS: The heterogeneity in the use of outcome measures across ALS randomized controlled trials was demonstrated, in addition to the infrequent use of MUNE. MUNE results demonstrated moderate intra- and inter-rater reliability for control subjects in the UT, although less favorable results were found overall for inter-rater reliability. Application of DE-STA MUNE to the UT in subjects with ALS demonstrated consistently high intra-rater reliability, the ability to detect the underlying pathophysiology of the disease, and a moderate degree of sensitivity to change for MUNE results. Further evaluation found needle electrode depth to significantly influence the results of the technique, with suggestions made for improved standardization of the protocol. SIGNIFICANCE: These studies were novel in their evaluation of MUNE in the proximal, potentially clinically relevant UT. The studies mark the first evaluations of the reliability and sensitivity to change of DE-STA MUNE in subjects with ALS, finding application to the UT to be practical and promising for use as an outcome measure. Implementation of proposed improvements to the protocol may aid in further establishing DE-STA MUNE for use as an outcome measure in studies of ALS

The effects of Hip Abductor Fatigue on Low Back Pain Development during Prolonged Standing

The goal of this thesis was to use hip abductor fatigue to perturb those who do and do not develop pain from standing and determine changes in muscular and postural responses. Forty young healthy participants performed two sessions of standing work for two hours each. Participants performed a side-lying leg raising exercise to fatigue prior to one of the standing sessions, the other session acted as a control. Surface electromyography (EMG) of six muscles bilaterally, motion capture of the trunk and lower limbs, and force plate data under each foot were measured continuously during each standing session. Self-reported pain and isometric hip abductor strength were assessed at discrete time points using 100 mm visual analog scales and uni-axial force transducers respectively. Participants were classified as pain developers (PDs) or non-pain developers (NPDs) based on a 10 mm threshold in low back pain scores during the control session. PDs (16/40) reported decreases in low back pain while standing during the fatigue session (10.9 ± 11.7 mm reduction) while NPDs reported minimal changes in pain with fatigue (1.5 ± 3.9 mm increase). Decreases in trunk (1033.9 ± 528.6 %MVIC reduction in first hour) and gluteal cocontraction indices (398.8 ± 792.4 %MVIC decrease in the 15 minute block) and increases in the number of anterior-posterior centre of pressure fidgets (13.5 ± 25.4 increase in the 30 minute block) were observed in the first hour of the fatigue session in PDs. Female PDs had more posterior pelvic tilt with fatigue (3.9 ± 9.2° more posterior with fatigue from 30 to 90 minutes), distinguishing them from male PDs (7.0 ± 11.3° more anterior with fatigue from 15 to 120 minutes). Both pain groups had similar EMG frequency shifts and strength lost due to fatigue. NPDs had longer times to fatigue than PDs (NPDs: 20.1 ± 11.2 minutes; PDs: 18.7 ± 9.3 minutes; p = 0.0106). This study provides evidence that the hip abductor musculature is likely one causative factor in the low back pain developed from standing. Also, PDs had fatiguing characteristics of persons suffering from chronic low back pain, only without any pain present

EMG Biofeedback Videogame System for the Gait Rehabilitation of Hemiparetic Individuals

Gemstone Team CHIPWe report a novel approach to electromyographic (EMG) biofeedback for post-stroke hemiparetic gait rehabilitation, using a videogame. An integrated hardware/software system facilitates gameplay of Tiger Woods PGA Tour 2004 in driving range mode by performing rehabilitation exercises. Real-time visual EMG biofeedback is provided as the patient performs exercises. Custom-built bioamplifiers and software collect, amplify, and filter the surface EMG signals from six lower-limb muscles, and score them by feature extraction. The ball is driven a distance proportional to each score. Exercises are scored by comparing the patient's EMG activation with target profiles. The user-friendly system is controlled by prompts on a personal computer. We envision two major benefits from this system. First, the biofeedback is offered in real-time, in a clear, intuitive form, and coupled with task-specific motions. Second, we hypothesize that adopting rehabilitation exercises to control a fun videogame will lead to greater adherence to the exercise regime, with accompanying improvements in gait

Evaluating Neuromuscular Function of the Biceps Brachii after Spinal Cord Injury: Assessment of Voluntary Activation and Motor Evoked Potential Input-Output Curves Using Transcranial Magnetic Stimulation

Activation of upper limb muscles is important for independent living after cervical spinal cord injury (SCI) that results in tetraplegia. An emerging, non-invasive approach to address post-SCI muscle weakness is modulation of the nervous system. A long-term goal is to develop neuromodulation techniques to reinnervate (i.e. resupply nerve to) muscle fiber and thereby increase muscle function in individuals with tetraplegia. Towards this goal, developing monitoring techniques to quantify neuromuscular function is needed to better direct neurorehabilitation. Assessment of voluntary activation (VA) is a promising approach because the location of the stimulus can be applied cortically using transcranial magnetic stimulation (TMS) or peripherally (VAPNS) to reveal what levels of the nervous system are disrupting the innervation of muscle fibers. Voluntary activation measured with TMS (VATMS) can indicate deficits in voluntary cortical drive to innervate muscle. However, measurement of VATMS is limited by technical challenges, including the difficulty in preferential stimulation of cortical neurons projecting to the target muscle and minimal stimulation of antagonists. Thus, the motor evoked potential (MEP) response to TMS in the target muscle compared to its antagonist (i.e. MEP ratio) may be an important parameter in the assessment of VATMS. Using current methodology, VATMS cannot be reliably assessed in patient populations including individuals with tetraplegia. The overall purpose of this work was to investigate novel TMS-based methods to evaluate neuromuscular function after spinal cord injury. First, we developed and evaluated new methodology to assess VATMS in individuals with tetraplegia. The objective of the first study was to optimize the biceps/triceps MEP ratio using modulation of isometric elbow flexion angle in nonimpaired participants and participants with tetraplegia following cervical SCI (C5-C6). We hypothesized that the more flexed elbow angle would increase the MEP ratio. The MEP ratio was only modulated in the nonimpaired group but not across the entire range of voluntary efforts used to estimate VATMS. However, we established that VATMS and VAPNS in individuals with tetraplegia were repeatable across days. In a second study, we aimed to optimize MEPs during the assessment of VATMS using paired pulse TMS to elicit intracortical facilitation and short-interval intracortical inhibition. We hypothesized that intracortical facilitation would lead to an increased MEP ratio compared to single pulse and that short-interval intracortical inhibition would lead to a lower MEP ratio. The MEP ratio was modulated in both groups but not across the entire range of voluntary efforts, and did not affect VATMS estimation compared to single pulse TMS. Paired pulse TMS outcomes revealed abnormal patterns of intracortical inhibition in individuals with tetraplegia. Further, VATMS was sensitive to the linearity of the voluntary moment and superimposed twitch relationship. Linearity was lower in SCI relative to nonimpaired participants. We discuss the limitations of VATMS in assessing neuromuscular impairments in tetraplegia. In a third study, we aimed to collect MEP input-output curves of the biceps in SCI and nonimpaired and evaluate curve-fitting methodology as well as their repeatability across sessions. We hypothesized that slopes would be greater in the SCI group compared to nonimpaired. Slopes obtained with linear regression were greater in tetraplegia compared to nonimpaired participants, suggesting compensatory reorganization of corticomotor pathways after SCI. Linear regression accurately represented the slope of the modeled data compared to sigmoidal function curve-fitting method. Slopes were also found to be repeatable across days in both groups. In a fourth study, we aimed to implement a low-cost navigated TMS system (\u3c $3000) that uses motion tracking, 3D printed parts and open-source software to monitor coil placement during stimulation. We hypothesized that using this system would improve coil position and orientation consistency and decrease MEP variability compared to the conventional method when targeting the biceps at rest and during voluntary contractions across two sessions in nonimpaired participants. Coil orientation error was reduced but the improvement did not translate to lower MEP variability. This low-cost approach is an alternative to expensive systems in tracking the motor hotspot between sessions and quantifying the error in coil placement when delivering TMS. Finally, we conclude and recommend future research directions to address the challenges that we identified during this work to improve our ability to monitor neuromuscular impairments and contribute to the development of more effective neurorehabilitation strategies

Isolated lumbar extension exercise as an intervention for chronic low back pain

Low back pain (LBP) is highly prevalent, generally categorised as ‘non-specific’ as clear diagnosis for pain is often absent, and further categorised into acute, sub-acute and chronic, with 69-75% of acute cases developing into chronic. This chronic LBP population accounts for the majority of economic costs worldwide associated with LBP. Although LBP is often ‘non-specific’, many physical dysfunctions are associated with it. Thus LBP can be regarded as multifactorial in nature. Dysfunctions include, but are not limited to: deconditioning of the lumbar extensor musculature, limited range of motion (ROM), gait abnormality and disc disorders. The novel approach of this thesis was to consider lumbar extensor deconditioning, LBP and its associated physical dysfunctions within a multifactorial framework, and the potential improvement of associated dysfunctions from intervention using isolated lumbar extension (ILEX) specifically aimed at addressing lumbar extensor deconditioning. Findings from three empirical studies are reported. The first examined limited ROM ILEX exercise compared with full ROM exercise. Results from this study support that limited ROM training is as effective as full ROM training at improving full ROM ILEX strength, pain and disability. The second study examined the effects of ILEX exercise upon lumbar spine kinematic waveform pattern variability during gait. Results from this study demonstrate that ILEX exercise significantly improves sagittal plane variability in chronic LBP participants. The final study examined the effects of ILEX exercise upon disc hydration determined indirectly through measurement of spinal height using seated stadiometry. Results from this study showed improved ILEX strength, pain and disability but did not demonstrate improvement in disc hydration. These results provide evidence for adopting a multifactorial conceptualisation of LBP in the use of ILEX exercise as a treatment. It is concluded that a wide range of improvements including pain, disability and various aspects of function relating to the multifactorial model are possible through use of a single minimal intervention involving ILEX. This conclusion has potential implications for considering direction of treatments from clinicians towards chronic LBP. Such a minimal intervention offering a wide range of benefits may reduce the need for costly and complex multi-disciplinary interventions