The relative contributions of muscle deformation and ischaemia to pressure ulcer development

Pressure ulcers are localised areas of soft tissue breakdown that develop over bony prominences as a result of sustained mechanical loading. They are particularly common in bedridden and wheelchair-bound individuals, and represent one of the most common secondary complications in spinal cord injured subjects. A specific form of pressure ulcers is termed deep tissue injury (DTI), which is defined as pressure-related injury to subcutaneous tissues such as skeletal muscle, initially under intact skin. DTI represents a severe problem, because tissue damage at the skin surface only becomes apparent at an advanced stage, and is associated with a variable prognosis. Therefore, early identification and subsequent treatment of DTI are critical to reduce comorbidities and the financial and manpower burdens associated with treatment. This requires a better understanding of its underlying aetiology, in order to develop appropriate risk assessment tools and early detection methods. Therefore, the main goal of the present thesis was to study the aetiology of DTI. In addition, some explorative studies were performed to examine potential methods for the early detection of DTI. The aetiological factors were investigated using a combination of experiments and numerical models. This involved an established rat model for DTI that has previously been used to study the effects of deformation due to 2 h continuous loading. In the present thesis, different loading regimens were applied to further investigate the role of deformation. In addition, a previously developed finite element model to estimate muscle deformations during loading, was substantially improved to enable a local comparison of deformation with damage. Furthermore, the duration of the experiments was extended to 6 h to investigate the effects of ischaemia and reperfusion. It was found that deformation is the primary trigger for muscle damage for loading periods up to 2 h when a specific deformation threshold is exceeded. Ischaemia started to cause changes in muscle tissue between 2-4 h loading. Therefore, the damage development in skeletal muscle during prolonged loading is determined by deformation, ischaemia, and reperfusion, each mechanism exhibiting a unique time profile. The developed methods were also applied to a porcine model for DTI to investigate the deformations of the different soft tissues of the buttocks during loading. In this study, it was shown that the relative mechanical properties of the different tissue layers have a large influence on the distribution of the internal deformations. The release of biochemical damage markers from injured muscle tissue into the circulation was studied to investigate the possibility of using these proteins for the early detection of DTI. Baseline variations of creatine kinase, myoglobin, heart-type fatty acid binding protein, and C-reactive protein were assessed in able-bodied and spinal cord injured human volunteers. These variations were small compared to the predicted increase in biomarker concentrations during DTI development, indicating that this combination of markers may prove appropriate for the early detection of DTI. Moreover, a considerable increase in myoglobin concentrations in blood and urine was observed in a rat model for DTI after 6 h mechanical loading. The present findings have implications for clinical practice. In particular, it is important to minimise the internal tissue deformations in subjects at risk of DTI, such as present in subjects with spinal cord injury and those positioned on hard surfaces, such as stretchers or operating tables, for prolonged periods. Furthermore, the period of loading should be limited to prevent the accumulation of ischaemic damage. The observation of increased myoglobin levels in blood and urine after mechanical loading demonstrates the potential of using biochemical markers of muscle damage for the early detection of DTI. Moreover, the increase of myoglobin levels in urine suggests that a noninvasive approach for this screening method may be satisfactory

Enhancing Nervous System Recovery through Neurobiologics, Neural Interface Training, and Neurorehabilitation.

After an initial period of recovery, human neurological injury has long been thought to be static. In order to improve quality of life for those suffering from stroke, spinal cord injury, or traumatic brain injury, researchers have been working to restore the nervous system and reduce neurological deficits through a number of mechanisms. For example, neurobiologists have been identifying and manipulating components of the intra- and extracellular milieu to alter the regenerative potential of neurons, neuro-engineers have been producing brain-machine and neural interfaces that circumvent lesions to restore functionality, and neurorehabilitation experts have been developing new ways to revitalize the nervous system even in chronic disease. While each of these areas holds promise, their individual paths to clinical relevance remain difficult. Nonetheless, these methods are now able to synergistically enhance recovery of native motor function to levels which were previously believed to be impossible. Furthermore, such recovery can even persist after training, and for the first time there is evidence of functional axonal regrowth and rewiring in the central nervous system of animal models. To attain this type of regeneration, rehabilitation paradigms that pair cortically-based intent with activation of affected circuits and positive neurofeedback appear to be required-a phenomenon which raises new and far reaching questions about the underlying relationship between conscious action and neural repair. For this reason, we argue that multi-modal therapy will be necessary to facilitate a truly robust recovery, and that the success of investigational microscopic techniques may depend on their integration into macroscopic frameworks that include task-based neurorehabilitation. We further identify critical components of future neural repair strategies and explore the most updated knowledge, progress, and challenges in the fields of cellular neuronal repair, neural interfacing, and neurorehabilitation, all with the goal of better understanding neurological injury and how to improve recovery

Neuromodulation in the treatment of symptoms of spinal cord injury

Introduction and purpose: Spinal cord injury may be associated with loss of motor and sensory functions, autonomic system functions and chronic pain. The development of technology has enabled the emergence of invasive and non-invasive methods of electrical and magnetic stimulation of the nervous system, which show a growing potential in the treatment of these symptoms in human and animal studies.The purpose of the study is a presentation of the most current studies about the selected methods of neuromodulation of the nervous system in the treatment of symptoms of spinal cord injury. Description of the state of knowledge: Neuromodulatory methods improve the functioning of patients affected by spinal cord injury. Studies on epidural stimulation of the spinal cord, transcranial magnetic stimulation, transcranial direct current stimulation transcutaneous spinal cord, and use of neuromodulation methods in combination with brain-machine interfaces stimulation show a reduction of chronic pain resistant to pharmacotherapy, improvement of motor limb function, respiratory function and bladder function. However, there are few large randomized studies with higher evidence strength.Conclusions: Neuromodulation is effective in the treatment of symptoms of spinal cord injury. Promising results should lead to further research to increase the strength of evidence for the effectiveness of these therapies, improve technology and a deeper understanding of the mechanisms behind their effectiveness

Infectious Complications after Spinal Cord Injury

Infectious diseases after spinal cord injury (SCI) are important. They can cause mortality and morbidity. The SCI patients usually stay in hospital or rehabilitation units for a long time, and this can cause several complications for them

A comparison of blood flow changes in tissues treated with therapeutic ultrasound and electrical stimulation

Context: Therapeutic ultrasound and electrical stimulation both claim to achieve many effects on the body, one of which is increasing blood flow in tissues. Research on electrical stimulation in regards to blood flow has shown both increased and decreased blood flow, due to the electrode placement and the muscular contractions elicited during the treatment, while research on therapeutic ultrasound has provided mixed results, some suggesting that increased blood flow is seen only with intolerable treatment intensities for the patients. The two treatments have not been previously compared in the same study. Objective: To compare radial artery blood flow following therapeutic ultrasound and electrical stimulation. Design: Cross-over study. Setting: University laboratory. Participants: Thirty-six healthy volunteers (22 females, 14 males; 21.19 ± 1.65 years; 170.96 ± 9.24 cm; 70.69 ± 11.54 kg). Interventions: The participants were randomly assigned to therapeutic ultrasound or electrical stimulation for the first treatment session. The participants returned seven days later to receive the treatment they did not receive during the first treatment session. Therapeutic ultrasound was delivered at 1MHz, continuous, 1.5 W/cm2, 10 minutes. The muscle belly of the flexor-pronator mass of the non-dominant forearm was used as the treatment site. Electrical stimulation was delivered at 2-Hz burst mode, 8 pulses/burst, pulse duration 180 microseconds, 15 minutes. The motor points of the flexor-pronator mass was used as the treatment site. This was determined by a visible contraction of the wrist flexors. Diagnostic ultrasound was used to measure radial artery blood flow volume. Main Outcome Measures: Radial artery blood flow volume was recorded before treatment, immediately post-treatment, 5 minutes post-treatment and 10 minutes post-treatment. Results: There were no significant differences found between blood flow measurements when comparing therapeutic ultrasound and electrical stimulation. There were also no significant differences in blood flow when comparing measurements within therapeutic ultrasound. However, there was a significant decrease in blood flow found with electrical stimulation when comparing baseline to immediately post-treatment (P = 0.04) and 5 minutes post-treatment (P = 0.01), but not at 10 minutes post-treatment (P = 0.16). Conclusions: Electrical stimulation temporarily reduces blood flow in the radial artery immediately following treatment and at 5 minutes following treatment. Electrical stimulation is useful in temporarily reducing blood flow and therefore may be beneficial in the control of edema or effusion

Acute intermittent hypoxia - a novel non-invasive therapy that promotes regeneration akin to brief electrical stimulation in peripheral nerve repair

Peripheral nerve regeneration often results in poor functional outcomes, a reality we aim to change. Injured peripheral neurons mount an intrinsic repair response as they undergo regenerative neuronal reprogramming, which can be enhanced by brief electrical stimulation (ES) of the injured nerve at the time of surgical repair, resulting in improved regeneration in rodents and humans. However, this approach is invasive. Acute intermittent hypoxia (AIH) - breathing alternate cycles of regular air and air with ~50% normal oxygen levels (11% O2) is emerging as a promising non-invasive intervention that promotes respiratory and non-respiratory motor function in spinal cord injured rats and humans. However, this therapy has the potential to globally impact the nervous system beyond the motor system. Of note, hypoxic conditions can increase neural activity in injured sensory neurons and peripheral axons and promote repair. Thus, I hypothesized that an AIH paradigm similar to that used for spinal cord repair, will improve peripheral nerve repair in a manner akin to ES, including its impact on regeneration-associated gene (RAG) expression – a predictor of growth states. To this end, alterations in early RAG expression (growth-associated protein 43, brain-derived neurotrophic factor, hypoxia-inducible factor alpha and a neural specific growth- associated protein, superior cervical ganglion 10) were examined for rats that had undergone tibial nerve transection and repair with either 2 days of normoxia treatment or AIH treatment begun two days post-repair, or 1 hour continuous ES treatment (20 Hz) at the time of repair. Three days post-repair, AIH or ES treatments effected significant and parallel elevated RAG expression relative to normoxia control treatment, most evident at the growing axon front. Behavioural, thermal and mechanical sensitivity assessments revealed that neither ES nor AIH elevated regeneration-associated pain states. Finally, ES showed significant impacts on functional recovery relative to normoxia controls in mid (25 day)- and late (70 day)-regeneration stages and AIH in mid (25 day)-regeneration stages. These indicators of an enhanced regenerative state for AIH and ES were supported by significantly increased numbers of newly myelinated fibers detected 20 mm distal to the tibial nerve repair site at 25 days post nerve repair. Collectively, these results support a role for brief AIH treatment, as a promising noninvasive adjunct therapy for improved peripheral nerve repair in a manner consistent with that observed with the more invasive direct nerve stimulation