Deputy Director and Foundation Scientist, NeuRA
Senior Principal Research Fellow, NHMRC
Conjoint Prof, UNSW
Honorary Prof, USyd and UQld
+612 9399 1617
Simon Gandevia (MD PhD DSc FAA FRACP) trained at the University of New South Wales and the Prince Henry Hospital. He has broad research interests in human movement control and he has used a wide range of techniques to examine fundamental aspects of pathophysiology in human neuroscience and clinical medicine. His work often sits at the interface between medicine and basic human neurophysiology.
Professor Gandevia is one of the four Founding Scientists of the Prince of Wales Medical Research Institute (in 1992), which was later renamed NeuRA. He was also a founder of the 3T Clinical Research Imaging Centre and is a Clinical Neurophysiologist at the Prince of Wales Hospital. He has served on many editorial boards, including the Journal of Physiology (1993-2000; 2011-) and is currently a Senior Editor. He is currently Associate Editor for the Journal of Applied Physiology (since 2005). His clinical work includes patients with neuromuscular disorders and those with spinal cord injury.
Spinal cord injury (SCI) results in the loss of function to not only voluntary motor control, but also to the regulatory systems that control bodily processes. Orthostatic (postural) hypotension (OH) is a common clinical feature in SCI patients, affecting up to 73% of patients with cervical spine and upper thoracic spine injuries during mobilisation and postural changes. This often results in symptoms of dizziness, light-headedness, fatigue and confusion, in turn limiting individual participation in physical rehabilitation and restricting progress towards regaining function and independence.
Therapeutic interventions are centred around ameliorating symptoms of OH; however, options for patients remain limited. Non-pharmacological treatments have had little success at treating hypotension in the long-term, while pharmacological interventions are used only when necessary as they may contribute to hypertension and even worsen episodes of autonomic dysreflexia, a life-threatening condition.
Functional Electrical Stimulation (FES) is one of the only interventions that has been shown to display some benefit in improving OH. Recently, stimulation of the lower limbs has been shown to acutely increase blood pressure in patients with SCI. Our recent projects have involved the use of FES applied over the abdominal muscles, termed abdominal FES, for SCI patients at risk of respiratory complications with promising results. As this same population is at risk of orthostatic hypotension, this study aims to determine whether abdominal stimulation can also be used to help this condition.
Based on our previous research, we believe that abdominal FES will increase blood pressure acutely during an orthostatic challenge in individuals with acute spinal cord injury, allowing for a longer time spent in a standing position. This will facilitate more effective rehabilitation, therefore improving quality of life and decreasing associated medical complications.
While tetraplegia is commonly associated with paralysis of all four limbs, paralysis also affects the major respiratory muscles, namely the diaphragm, abdominal and intercostal muscles. The reduction in respiratory function results in approximately 40% of tetraplegic patients requiring mechanical ventilation in the acute stage (first six weeks) of injury to support respiration. The use of mechanical ventilation increases lifelong morbidity and mortality, delays rehabilitation, results in longer hospital stays and costs the health care provider an additional $2,000 per patient per day.
Surface electrical stimulation of the abdominal muscles, termed Abdominal Functional Electrical Stimulation (FES), can contract the abdominal muscles, even when paralysed. We have shown that surface FES of the abdominal muscles, termed Abdominal FES, improves respiratory function in tetraplegia, and respiratory function is a known predictor of mechanical ventilation time. Dr McCaughey’s pilot work also shows that eight weeks of abdominal FES is a feasible method to reduce mechanical ventilation time in acute tetraplegia.
Despite these positive results, a lack of data from randomised control trials, and lack of a standard Abdominal FES protocol, has prevented this technology from being adopted as a standard clinical treatment.
This project will provide the first information on the effectiveness and cost-effectiveness of Abdominal FES to reduce mechanical ventilation duration in tetraplegia. In addition, it will provide detailed information about respiratory function and its impact on quality of life in tetraplegia.
This is an international collaboration brings together leading research and medical teams from: Neuroscience Research Australia, the Prince of Wales Hospital, Royal North Shore Hospital, Austin Health and Fiona Stanley Hospital in Australia; The Indian Spinal Cord Injury Centre and the Christian Medical College, Vellore, in India; The Queen Elizabeth National Spinal Injuries Unit and the University of Glasgow in Scotland; Middlemore Hospital in Auckland, New Zealand, and the University of Alberta and McMaster University in Canada.
There are currently over 20,000 people living with Multiple Sclerosis (MS) in Australia. Bowel and bladder problems, mainly in the form of constipation and urinary incontinence, affect more than half of these people. These problems have traditionally been managed using a combination of manual and pharmacological interventions. However, such solutions are usually only partially effective. Therefore, a non-invasive method of improving bowel and bladder function for people with MS is urgently needed.
The abdominal muscles play a major role during defecation and urination. Surface electrical stimulation of the abdominal muscles, termed Abdominal Functional Electrical Stimulation (Abdominal FES), has been shown to improve bowel function after spinal cord injury, with a case study suggesting this technique may also improve bowel function in MS. There is also limited evidence that Abdominal FES can improve bladder control.
We are currently undertaking the first significant study to investigate the effectiveness of Abdominal FES to improve the bowel and bladder function of people with MS. By making use of the most advanced motility testing system currently available, we hope to be able to definitively assess whether Abdominal FES could be a useful treatment solution for people with MS.
Approximately 33% of critically ill patients require mechanical ventilation to support respiration. During this time the major respiratory muscles, namely the diaphragm, abdominal and intercostal muscles, weaken. This vicious cycle leads to difficulty in separating patients from mechanical ventilation, increased mortality, and more readmissions to intensive care. Interventions that maintain respiratory muscle strength and reduce atrophy during mechanical ventilation are likely to reduce ventilation duration, complications and costs, and improve quality of life.
The abdominal muscles are the primary muscle group used during forced exhalation. We have shown that surface Functional Electrical Stimulation (FES) of the abdominal muscles, termed Abdominal FES, can improve respiratory function and assist weaning from mechanical ventilation in spinal cord injury. We hypothesise that Abdominal FES in critically ill patients will reduce diaphragm and abdominal muscle atrophy, with the long term goal of this project to demonstrate reduced mechanical ventilation duration.
We are currently conducting a pilot study at the Prince of Wales Hospital, Sydney, to investigate whether Abdominal FES is a feasible technique for reducing mechanical ventilation duration in critical illness. This work is being supported by our American project partners, Liberate Medical.
While tetraplegia is often characterized by paralysis of all four limbs, paralysis also affects the major respiratory muscles, namely the diaphragm and abdominal and intercostal muscles. This reduces respiratory function, with associated respiratory complications, such as pneumonia and atelectasis. Such complications are a leading cause of illness and death for the tetraplegic population. Up to 68% of patients with tetraplegia have a respiratory complication in the first 6 weeks (i.e. the acute stage) of injury. A reduction in respiratory complications in acute tetraplegia would decrease illness and death, reduce rehabilitation time, improve quality of life, and result in a large cost saving for global health systems.
Surface electrical stimulation of the abdominal muscles, termed Abdominal Functional Electrical Stimulation (FES), can contract the abdominal muscles, even when paralysed. We have shown that the repeated application of Abdominal FES improves the respiratory function of people with tetraplegia. However, while respiratory function is a predictor of respiratory complications in tetraplegia, evidence that Abdominal FES reduces respiratory complications is only anecdotal. We will undertake the first prospective, multi-centre, randomised placebo controlled trial, to determine whether Abdominal FES reduces respiratory complications in acute tetraplegia.
Definitive evidence of the effectiveness of Abdominal FES to reduce respiratory complications in tetraplegia will drive the rapid worldwide translation of this low cost and easily applied technology for this vulnerable patient group. This will decrease illness and death, reduce rehabilitation time, improve quality of life, and result in a large cost saving for global health systems.
This international collaboration brings together leading research and medical teams from: Neuroscience Research Australia, the Prince of Wales Hospital, and the Royal North Shore Hospital in Australia; The Indian Spinal Cord Injury Centre; Chang Mai University Hospital in Thailand and The Queen Elizabeth National Spinal Injuries Unit and the University of Glasgow in Scotland.
Obstructive sleep apnoea (OSA) is a common disorder characterised by repetitive narrowing and collapse of the upper airway during sleep. It is associated with daytime sleepiness, neurocognitive impairment, and a variety of adverse cardiovascular consequences. The first line treatment for OSA is continuous positive airway pressure (CPAP) therapy. If tolerated, CPAP is highly effective in reducing sleep disordered breathing events. However, up to 50% of OSA patients are unable to tolerate CPAP therapy leaving many OSA patients without treatment.
Previous studies indicate that in selected obstructive sleep apnea participants a standard dose of a z-drug can shift the threshold for awakening during sleep (arousal) whilst maintaining the upper airway muscle activity required to keep the airway open. This study aims to investigate the effects of different doses of sleeping pills (Z-drugs) on how easily people wake up when the airway narrows during sleep, the activity of a major muscle located under the tongue (genioglossus) and obstructive sleep apnoea (OSA) severity and symptoms.
Not only are the breathing muscles controlled automatically from the brainstem and motor cortex, but they can be activated in response to emotion, e.g. during laughing and crying. We plan to investigate the neural pathways involved in emotional breathing in healthy volunteers.
This basic science project aims to examine the behaviour of human motoneurones during sustained activation to reveal their mechanisms of recovery after activation. We will take the fundamental findings from this study and compare the behaviour of motoneurones innervating muscles affected by neurological injury such as spinal cord injury and stroke.
Respiratory complications are the major cause of death for people with spinal cord injuries. People with a high level spinal cord injury are 150 times more likely to die from pneumonia than the general population. This is because after high level spinal cord injury, people have a reduced ability to cough and to clear secretions from the lungs. The major group of muscles that produce a cough are the abdominal muscles. If the abdominal muscles are paralysed after spinal cord injury then the strength of the cough will be severely reduced. In our lab, we are looking at ways to improve cough in people with spinal cord injury by using surface functional electrical stimulation of the abdominal muscles. We have shown that this type of stimulation can improve cough significantly. We are now looking for ways to further improve cough through muscle training as well as ways to develop a portable stimulator that would allow independent activation of a cough.
Breathing is a complex motor task that needs to be coordinated at all times while we eat, speak, exercise and even during sleep. The breathing muscles are controlled automatically from the brainstem during normal breathing but can also be controlled voluntarily from the motor cortex. The way these two drives to the breathing muscles interact is still not well understood. While there is some evidence that there are at least two independent pathways, and that integration of the pathways occurs at the spinal cord, there is some uncertainty about whether these pathways may have some interaction in the brainstem. Our current experiments are looking at voluntary and involuntary drive to the breathing muscles to try to answer this fundamental question about the neural control of breathing. In addition we are looking at the potential cortical contributions to resting breathing in respiratory disorders.
Our recent studies of the control of breathing muscles have shown a strong link between neural drive and mechanical action of the muscle. We showed that for a number of breathing muscles, the neural drive is directed to the muscles with the best mechanical effect for breathing. We termed this link between mechanics and neural drive ‘neuromechanical matching’. It is a new principle of muscle activation that allows for metabolically efficient activation of the muscles. This basic research finding is now leading to further studies in patients with respiratory disorders where muscle mechanics have changed. Chronic obstructive pulmonary disease is one such disease, where muscle mechanics are known to change. Our new studies will look at whether these patients have “adapted” to the changed muscle mechanics or whether their muscles may be activated inefficiently.
After cervical spinal cord injury (SCI), the respiratory muscles are partly or completely paralysed. This has two major clinical consequences: a decreased ability to get air into the lungs and a decreased ability to cough and remove secretions. This results in a lifetime of recurrent respiratory tract infections (2/year/person) that often progress to pneumonia with frequent and extended hospital admissions. People with cervical SCI are 150 times more likely to die from respiratory complications than the general population, as many as 28% die within the first year after injury. For those that survive the first year, a cervical SCI has a lifetime cost of $9.5million, a large proportion of which is attributed to respiratory-related complications. A recent longitudinal study of people with cervical SCI showed that respiratory muscle weakness is associated with incidental pneumonia. Respiratory muscle weakness also causes dyspnoea (breathlessness) and sleep-disordered breathing, which is 4-10 times more prevalent in people with SCI than the able-bodied population. Therefore, there is an urgent need to identify a simple and cost-effective treatment for respiratory muscles weakness to prevent respiratory complications after SCI, improve quality of life and reduce the burden on the healthcare system.
Our primary aim is to determine definitively the effectiveness of training on respiratory muscle strength, respiratory physiology and health outcomes. To do this we will conduct a randomised controlled trial 2 times bigger than the largest previous study, of respiratory muscle resistive load training in individuals with acute and chronic cervical SCI. The project will provide critical new knowledge about the efficacy of a simple and inexpensive respiratory muscle training regime, which can be applied immediately in the hospital and community, to minimise respiratory morbidity in people with SCI. This project also provides a unique opportunity to investigate other consequential effects of long-term respiratory muscle training that have never been studied in people with SCI. These include effects on cough efficacy, sleep-disordered breathing, breathlessness, respiratory morbidity, respiratory health and neural drive to the diaphragm, as well as quality of life.
We have developed novel imaging methods to measure the stiffness and movement of the upper airway muscles, and are using these together with measures of pharyngeal sensation, and electromyography to determine the patient-specific causes of obstructive sleep apnoea. We aim to use this information to tailor treatments for patients. One such treatment is a mandibular advancement splint, but currently it’s not possible to predict who will benefit from use a splint. We have a major project that aims to predict splint treatment outcome, based on our novel imaging methods.• Honours and PhD projects are available to study the neural, biomechanical and physiological aspects of obstructive sleep apnoea, including computational modelling
DR PHU HOANG
NeuRA Post-Doctoral Fellow, MS Senior Physiotherapist
: +612 9399 1832
DR MARTIN HÉROUX Research officer
DR PETER NICKOLLS
Honorary Senior Research Officer
: +612 9399 1013
DR ANNE BUTLER Research Officer
DR CHAMINDA LEWIS PhD student
DR RACHEL MCBAIN Postdoctoral fellow
DR CHAMINDA LEWIS PhD student
Four weeks of isometric strength training of the elbow flexors increased muscle strength and voluntary activation, without a change in the muscle. The improvement in activation suggests that voluntary output from the cortex was better able to recruit motoneurons and/or increase their firing rates. The lack of change in CMEPs indicates that neither corticospinal transmission nor motoneuron excitability was affected by training.
In vivo measurements of muscle architecture provide insight into inter-individual differences in muscle function and could be used to personalise musculoskeletal models. When muscle architecture is measured from ultrasound images, as is frequently done, it is assumed that fascicles are oriented in the image plane and, for some measurements, that the image plane is perpendicular to the aponeurosis at the intersection of fascicle and aponeurosis. This study presents an in vivo validation of these assumptions by comparing ultrasound image plane orientation to three-dimensional reconstructions of muscle fascicles and aponeuroses obtained with diffusion tensor imaging (DTI) and high-resolution anatomical MRI scans. It was found that muscle fascicles were oriented on average at 5.5±4.1° to the ultrasound image plane. On average, ultrasound yielded similar measurements of fascicle lengths to DTI (difference <3mm), suggesting that the measurements were unbiased. The absolute difference in length between any pair of measurements made with ultrasound and DTI was substantial (10mm or 20% of the mean), indicating that the measurements were imprecise. Pennation angles measured with ultrasound were significantly smaller than those measured with DTI (mean difference 6°). This difference was apparent only at the superficial insertion of the muscle fascicles so it was probably due to pressure on the skin applied by the ultrasound probes. It is concluded that ultrasound measurements of deep pennation angles and fascicle lengths in the medial gastrocnemius are unbiased but have a low precision and that superficial pennation angles are underestimated by approximately 10°. The low precision limits the use of ultrasound to personalise fascicle length in musculoskeletal models.