Award Partner: International Collaboration on Repair Discoveries (ICORD)

Improving motor prognosis after spinal cord injury

Spinal cord injury (SCI) leads to devastating muscle paralysis. My research has shown that paralysis is due, not only to interruption of communication across the damaged spinal cord, but also because of damage to the nerves and muscles outside the spinal cord, which are equally as important in producing strength. This unrecognized damage may influence prognosis and how a patient responds to treatment. Unfortunately, we do not routinely test the health of these nerves and muscles. This makes it very challenging for doctors to provide patients with accurate information about prognosis and also for patients to make proper decisions about treatment options. My project will showcase the health of nerves and muscles after SCI, using a combination of routine clinical and special laboratory techniques. This information will lead to:

  1. Identification of those at risk of nerve and muscle damage.
  2. Routine assessment of nerve/muscle health in clinical practice.
  3. The development of a tool to help patients make informed decisions about treatment.

The project will be conducted by my team at GF Strong Hospital and with collaborators in three other Canadian centres.

Transcutaneous spinal cord stimulation for treating neurogenic bladder dysfunction following spinal cord injury

As much as 80 percent of people with a spinal cord injury (SCI) develop urinary bladder problems. Recovery of bladder function is consistently rated as a top treatment priority for people with SCI. Left unmanaged, bladder dysfunction can result in frequent urine leakage or unwanted urine retention that often cause kidney or urinary tract infections which drastically reduce overall quality of life. Despite the prevalence of this issue, treatment for restoring bladder function remains under-emphasized in SCI research. Of even greater concern are consequences associated with rapid, and often life-threatening, increases in blood pressure triggered by bladder care. Electrical spinal cord stimulation via surgically implanted electrodes is a potential treatment option that has been shown to promote functional recovery after SCI by modulating silent spinal circuits. However, the surgical implantation of electrodes and the stimulator is invasive, expensive and has inherent risks. We propose to improve bladder function and prevent associated blood pressure surges via non-invasive spinal cord stimulation using electrodes placed over the skin, thereby minimizing patient risk and obviating the need for invasive and expensive surgery.

Servo-controlled device to maintain physiological functioning

300,000 individuals live with spinal cord injury (SCI) in the US alone, of which 180,000 suffer from orthostatic hypotension, sudden falls in blood pressure upon standing. Such dysregulated blood pressure can also be caused by multiple sclerosis, autonomic failure, autonomic neuropathy, or neurological cancers. A high quality, efficient, and cost effective method is needed to help these individuals regulate their blood pressure.

Dr. Krassioukov has developed a device and algorithm for controlling autonomic processes in patients using electrical stimulation, based on the surprising discovery that electrical stimulation of the spinal cord circuitry caudal to SCI can control the activity of disconnected sympathetic circuitry to regulate blood pressure. The device can be individualized, and electrical output may increase or decrease based on the information received from the patient’s physiological monitor.

Dr. Krassioukov’s product may improve patients’ control of autonomic functions such as dysregulated blood pressure due to SCI or other injuries or diseases, improving their quality of life and ability to manage symptoms, at a lower cost and with improved effectiveness than current methods.

The acute impact of spinal cord injury on cardiac function, and novel hemodynamic management in SCI patients

Following acute spinal cord injury (SCI), one of the only presently available neuroprotective strategies is to try and optimize management of spinal cord blood flow. This treatment specifically aims to immediately increase blood flow to the injured spinal cord tissue to prevent the spread of injury to surrounding spinal cord tissues.
Currently, vasopressors are administered to increase blood pressure to a similar threshold in all patients; however, its efficacy in improving neurological outcomes has not been consistent, and in some patients has been found to actually worsen outcomes. A more optimized and individualized approach to blood flow management in SCI patients is needed.

High-thoracic SCI immediately impairs the brainstem and neural control of the heart. Our pilot data suggest this decentralization of the heart immediately impairs cardiac function, which could have significant implications for the acute management of blood flow in SCI patients. Dr. Williams will investigate the immediate and acute cardiac responses to high-thoracic SCI, and determine whether improvements to cardiac function can improve spinal cord blood flow and neurological outcomes in SCI patients.

Dr. Williams will conduct translational studies utilizing a porcine model of SCI. She will test the efficacy of potential novel management strategies, including restoring cardiac function alone or in combination with vasopressor therapy. A simultaneous study will look at acutely injured individuals with SCI at Vancouver General Hospital, examining heart function during the first three days after injury.

To date, very little work has characterized the impact of SCI on cardiac function in the initial period following injury. Combining invasive and integrative studies in pigs and humans provides us with the unique opportunity to conduct highly translatable studies that could have an immediate impact on SCI patient outcomes.

 

End of Award Update – July 2022

Most exciting outputs
Our research to date has identified how high-level spinal cord injuries (i.e. at or above the mid-back level) impact the heart immediately after the injury occurs. We found that those injuries impact the heart’s output within the first hours post-injury, and further identified a treatment that could harness the heart to support blood pressure and potentially reduce secondary damage to the spinal cord.

 

Impacts so far
The award has allowed us to examine alternative approaches to treating acute spinal cord injury which could ultimately improve outcomes if that approach is effective in the clinical setting. Moreover, as a trainee this award has provided the critical opportunity for me to expand my skillset in the realms of clinical and pre-clinical research, and apply gold-standard techniques to answer questions about the heart that have traditionally been overlooked in the field of spinal cord injury research.

 

Potential future influence
With the support of this award I have made significant strides in my training toward becoming an established cardiovascular researcher. First, it has allowed me to expand my expertise in the heart and its neural control. Second, I have gained invaluable experience in clinical and pre-clinical research, which truly round out my training as a physiologist. Finally, I have been able to produce and output impactful research across those domains and in doing so built strong collaborations with local and international leaders in these respective fields.

 

Next steps
We have yet to publish additional research that has stemmed from this award, looking at the long-term benefits of heart-focused approaches to treating spinal cord injury, and would like to pursue opportunities to implement such an approach in the clinical setting.

 

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