An estimated 86,500 people are currently living with spinal cord injury (SCI) in Canada, and approximately 4,300 more will experience SCI each year. In persons with SCI, the bladder can't receive or send the signals required for normal organ function, and 80 percent of persons with SCI are affected by acute or chronic urinary tract complications that negatively influence their health, quality of life and impact their life expectancy. Currently, evaluation of bladder function is limited to periodic urodynamic testing (UDS), an invasive procedure that requires patients to have catheters inserted into the urethra and rectum. Besides being a painful and inconvenient procedure, the invasive nature of this diagnostic method exposes patients to the risk of serious complications such as urinary tract infection, trauma and bleeding that may further complicate urinary tract conditions. Dr. Babak Shadgan is investigating the use of near-infrared spectroscopy (NIRS) as a novel non-invasive diagnostic method to evaluate the physiologic mechanisms underlying bladder dysfunction in people with SCI. Detecting when the bladder has filled to a given volume or size is essential to avoid accidental incontinence and also to prevent damage to the kidneys from backpressure secondary to a full bladder. NIRS is a non-invasive optical technique that uses light to monitor changes in tissue oxygenation and changes in blood supply to the bladder as the organ fills and empties. Using NIRS for bladder monitoring in this population will demonstrate both scientific relevance and commercial potential and will lead to the development of an NIRS device capable of more effective, more comprehensive, and safer evaluation of bladder dysfunction than current methodologies. The health care burden associated with bladder dysfunction secondary to SCI is considerable; hence, the further development of NIRS for monitoring devices and diagnostic techniques for persons with SCI has potential to reduce complications associated with current invasive tests and improve the standards of care in this population.
Research Location: Vancouver Hospital & Health Sciences Centre (UBC Hospital)
Survival and Cause of Death in the British Columbian Multiple Sclerosis Population
Multiple sclerosis (MS) is a relatively common neurological disease. Because of its chronic nature and because it typically first appears in people in their mid 20s to 30s, people with MS are usually expected to live for many years following disease onset. Little is known about survival expectations, predictors of long-term survival, how survival is influenced by MS drug therapies, and causes of death in this population. Ever since immunomodulatory therapies first became available to Canadian MS patients in the mid 1990s, there has been a rapid uptake of these drugs. These medications appear to be at least partially effective in modifying some aspects of the disease, such as relapses, but they are associated with significant side effects, require frequent injections, and are expensive. The long-term impact of treatment is unknown and opportunities to study treatment-naïve patients have diminished over the years, as there are fewer patients with MS who have not taken these therapies. In British Columbia, we have a valuable data resource that includes both unexposed (untreated) and treated MS patients.
Dr. Elaine Kingwell is combining several large, powerful, clinical and administrative longitudinal datasets, including the population-based BC MS clinical database (containing data from approximately 7,000 MS patients over a 30-year period), BC Ministry of Health medical services plan registration data, BC Vital Statistics death data and BC Cancer Agency data. She will use this data set to determine the long-term health impacts of MS and how they are influenced by immunomodulatory drugs. She will specifically compare the causes of death (including cancer, suicide, heart disease and infection) between people with MS and the general population.
Dr. Kingwell will also investigate cancer survival of MS patients in comparison to the general population, which is an area of some controversy. She will determine how frequently MS is listed as an underlying or contributing cause of death, which will help to facilitate planning and interpretation of population-based studies of MS mortality trends. Findings from this study will further our understanding of the role that MS plays in long-term health outcomes, such as cancer survival, and will broaden our existing knowledge of factors associated with longevity in MS. These results will also provide a vital estimate of the impact of immunomodulatory therapy on survival and specific causes of death for MS. The findings from this research will have a profound impact on the care, monitoring and treatment of the disease.
Role of ionotropic glutamate receptors in ischemic injury and dendritic spine dynamics
Inadequate blood supply (ischemia), resulting in neuronal cell death caused by stroke, cardiac arrest or profound hypotension is a leading cause of death and permanent disability. Brain damage resulting from ischemic injury typically manifests as the immediate loss of neurons within the ischemic core, surrounded by a region of brain tissue exposed to reduced blood flow and oxygen called the penumbra or peri-infarct region. This peri-infarct region has been the target of therapeutic protection following ischemic insult (e.g. stroke), and is thought to play a potentially critical role in functional recovery following stroke. Although the precise mechanisms of underlying delayed neuronal cell death are multi-faceted, the over-activation of N-methyl-D-spartate receptors (NMDARs), is known to have a key role in mediating neuronal injury in both in vitro and in vivo models of stroke and traumatic brain injury. Dr. Allen Chan is examining the role of selective NMDAR activation and blockade on dendritic spine dynamics immediately following a focal ischemic stroke, with the aid of established pharmacological treatments and in vivo brain imaging techniques. Dendritic spines are hypothesized to be key structural substrates within the penumbra that mediate plasticity changes necessary for functional recovery after stroke. Dr. Chan’s project will increase our understanding of the mechanisms and pathology of stroke injury with respect to the damage and death caused to pivotal brain cell connections called synapses, and ways to potentially alleviate this damage and death. In so doing, rescue and protection of damaged but repairable parts of the brain may lead to treatments that enhance functional recovery and therapies that directly impact patient health and quality of life.