Spinal Cord Injury

Background

EarlyStages keyA spinal cord injury (SCI) is an insult to the spinal cord, either by trauma or disease, which results in the disruption of signal transmission between the brain and the rest of the body. SCIs most often arise secondary to a traumatic event, such as a motor vehicle accident. Non-traumatic causes of SCI can be divided into intrinsic cord pathology and extrinsic factors. Intrinsic causes include spinal cord tumors, infection, neurodegenerative disease, and spinal cord vascular disease. Extrinsic causes are more common and include intervertebral disc disease and herniation, epidural hematoma, abscess, and malignancy.

Injuries to the spinal cord are classified as complete or incomplete, with complete injuries resulting in total loss of function below the level of the lesion. Conversely, various degrees of motor/sensory function are preserved in incomplete injuries. Symptoms can range from pain at the site of injury to complete paralysis.

The incidence of spinal cord injury in the United States is approximately 12,000 patients per year. As of 2010, it is estimated that about 265,000 Americans are living with SCI. Leading causes of mortality in those that do survive their initial injury are pneumonia, pulmonary embolism, or septicemia, with suicide and alcohol-related deaths also contributing significantly. Overall, life expectances for patients with SCI are increasing, but are still below the general population.

Current Treatment

Currently, there is no known method to reverse spinal cord damage. In patients with acute SCI, treatment involves:

  • Stabilizing vital signs and immobilizing the patient to prevent further damage
  • Surgery: may be used to remove fluid or tissue that causes extrinsic pressure on the spinal cord; remove bone fragments, disk fragments, or foreign objects; fuse broken spinal bones; or place spinal braces.
  • Traction: stabilizes the spine and brings it into proper alignment.
  • Medication: if given within 8 hours of injury, some patients experience improvement as with medications that reduce damage to nerve cells and decrease inflammation.

 

To reduce long-term effects, people with SCI may also benefit from rehabilitation including:

  • Physical and occupational therapy
  • Assistive devices
  • Exercise and diet strategies as excessive weight can further complicate SCI

 

In addition, several other strategies are currently being investigated as potential treatments of SCI including:

  • Spinal cord cooling: recent data shows that relatively mild levels of hypothermia induced after traumatic or compressive SCI provides some level of functional improvement and reduces histopathological damage.
  • Functional electrical stimulation (FES): provides synchronized electrical currents to neural tissues for the purpose of restoring neuromuscular, sensory and/or autonomic function (i.e. bowel, bladder, respiratory function).
  • Neural stem cells: may promote neural repair by secreting neuronal growth factors.

Focused Ultrasound Research

Pioneering preclinical research is currently being conducted on the use of FUS to aid in delivering genetic material across the blood-spinal cord barrier (BSCB). A 2015 study entitled “Gene Delivery to the spinal cord using MRI-guided focused ultrasound” by Kullervo Hynynen and collaborators at the University of Toronto and Sunnybrook Research Institute describes the use of FUS in combination with microbubbles to transiently open the BSCB which allowed for non-surgical, targeted gene delivery in a rat model. The mechanical effects of FUS disrupt the tight junctions between endothelial cells lining this barrier, thereby increasing permeability and enabling delivery of therapeutic compounds into the spinal cord. Microbubbles may be injected to better control this process and reduce the risk of damage to the vessel. This work complements earlier research suggesting that viral vector delivery of various growth factors (i.e. neurotrophin) after spinal cord injury may be useful to induce selective regeneration of damaged axons.

Notable Papers

Weber-Adrian D, Thévenot E, O'Reilly MA, Oakden W, Akens MK, Ellens N, Markham-Coultes K, Burgess A, Finkelstein J, Yee AJ, Whyne CM, Foust KD, Kaspar BK, Stanisz GJ, Chopra R, Hynynen K, Aubert I. Gene delivery to the spinal cord using MRI-guided focused ultrasound. Gene Ther. 2015 Jul;22(7):568-77.

Y.-S. Tung, F. Vlachos, J. A. Feshitan, M. A. Borden, and E. E. Konofagou, “The mechanism of interaction between focused ultrasound and microbubbles in blood-brain barrier opening in mice.,” J. Acoust. Soc. Am., vol. 130, no. 5, pp. 3059–3067, Nov. 2011.

C. X. Deng, “Targeted drug delivery across the blood-brain barrier using ultrasound technique.,” Ther. Deliv., vol. 1, no. 6, pp. 819–848, Dec. 2010.

     

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