03 Jul Spinal Cord Injury : Nerve Degeneration Occurs Within Months
MedicalResearch.com Interview with:
Dr Patrick Freund
Spinal Cord Injury Center Balgrist
University Hospital Zurich, University of Zurich
8008 Zurich, Switzerland
MedicalResearch.com: What are the main findings of the study?
Dr. Freund: Novel interventions targeting acute spinal cord injury (SCI) have entered clinical trials, but neuroimaging biomarkers reflecting structural changes within the central nervous system are still awaited. In chronic SCI, neuroimaging provided evidence of structural changes at spinal cord and brain level that could be related to disability. However, the pattern and time course of these structural changes and their potential to predict clinical outcomes is uncertain.
In a prospective longitudinal study, thirteen patients with acute traumatic SCI were assessed clinically and by longitudinal MRI (within five weeks of injury, after two, six and twelve months) and were compared to eighteen healthy controls. Cross-sectional cord area, cranial white matter (CST) and grey matter (cortex) volume decrease was evident at baseline and progressed over twelve months. Multi-parametric mapping of myelin sensitive magnetization transfer (MT) and longitudinal relaxation rate (R1) was reduced both within and beyond the areas of atrophic changes. Better neurological and functional outcomes were associated with less atrophic changes of the CST in both cord and brain.
MedicalResearch.com: Were any of the findings unexpected?
Dr. Freund: It was believed that anatomical changes, in terms of volume loss, occur slowly above the level of injury. Only in 2010 (Freund et al 2010, Brain) it was realized that the cross-sectional cord area had atrophied even many levels above the actual site of trauma. In the present study, that incorporated paraplegic and tetraplegic patients, a rapid decline of 7% of the cord area occurred already during the first year without any signs of deceleration. We were amazed that even the cranial corticospinal tract and sensorimotor areas showed significant volume loss. However, within the brain these changes followed a non-linear relationship. Crucially, less loss of nerve tissue above the level of injury identified those patients that showed a better and steeper recovery at 12 months follow-up.
MedicalResearch.com: What should clinicians and patients take away from your report?
Dr. Freund: Extensive upstream atrophic and microstructural changes of corticospinal axons and sensorimotor cortical areas occur as early as the first months after SCI and reveal a specific pattern of progression. Faster degenerative changes predicted a poorer recovery. Structural volumetric and microstructural MRI protocols remote from the site of SCI have the potential to serve as neuroimaging biomarkers to assess effects of therapeutic interventions at any given location within the CNS.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Dr. Freund: This study calls for the adoption of imaging biomarkers in future clinical trials as they have the potential to personalize the care of patients suffering from spinal cord injury. We call for a rapid adoption of these neuroimaging biomarkers in multicenter studies involving high-volume clinical centers.
MRI investigation of the sensorimotor cortex and the corticospinal tract after acute spinal cord injury: a prospective longitudinal study
Dr Patrick Freund PhD,Nikolaus Weiskopf PhD,Prof John Ashburner PhD,Katharina Wolf MD,Reto Sutter MD,Daniel R Altmann PhD,Prof Karl Friston PhD,Prof Alan Thompson MD,Prof Armin Curt MD
The Lancet Neurology – 2 July 2013
Irreversible tissue loss seen within 40 days of spinal cord injury
A spinal cord injury changes the functional state and structure of the spinal cord and the brain. For example, the patients’ ability to walk or move their hands can become restricted. How quickly such degenerative changes develop, however, has remained a mystery until now. The assumption was that it took years for patients with a spinal cord injury to also display anatomical changes in the spinal cord and brain above the injury site. For the first time, researchers from the University of Zurich and the Uniklinik Balgrist, along with English colleagues from University College London (UCL), now demonstrate that these changes already occur within 40 days of acute spinal cord injury. In light of this information, if you believe you have suffered a spinal cord injury, it is imperative that you are seen by a healthcare professional. You may need an x-ray at the very least to assess the extent of any potential injuries, please click here for more information. Additionally, depending on your unique circumstances: This means that anyone with conditions like this should file a spinal cord injury lawsuit as they could receive compensation for their injury.
Spinal cord depletes rapidly
The scientists studied 13 patients with acute spinal cord injuries every three months for a year using novel MRI (magnetic resonance imaging) protocols. They discovered that the diameter of the spinal cord had rapidly decreased and was already seven percent smaller after twelve months. A lesser volume decline was also evident in the corticospinal tract, a tract indispensable for motor control, and nerve cells in the sensorimotor cortex. The extent of the degenerative changes coincided with the clinical outcome. “Patients with a greater tissue loss above the injury site recovered less effectively than those with less changes,” explains Patrick Freund, the investigator responsible for the study at the Paraplegic Center Balgrist.
Gaining insights into effect of therapies
Treatments targeting the injured spinal cord have entered clinical trials. Gaining insights into mechanisms of repair and recovery within the first year are crucial. Thanks to the use of the new neuroimaging protocols, Freund says, we now have the possibility of displaying the effect of therapeutic treatments on the central nervous system and of rehabilitative measures more quickly. Consequently, the effect of new therapies can also be recorded more rapidly.
“This study is an excellent example of the value of combining the complementary expertise of the two universities,” says UCL’s Dean of Brain Sciences, Professor Alan Thompson, who is one of the senior authors of the study. “It provides exciting new insights into the complications of spinal cord trauma and gives us the possibility of identifying both imaging biomarkers and therapeutic targets.”
The findings are the result of a new three-year neuroscience partnership between the Neuroscience Centre Zurich (ZNZ) and UCL.
Patrick Freund, Nikolaus Weiskopf, John Ashburner, Katharina Wolf, Reto Sutter, Daniel R Altmann, Karl Friston, Alan Thompson, Armin Curt. MRI investigation of the sensorimotor cortex and corticospinal tract after acute spinal cord injury: a prospective longitudinal study. The Lancet Neurology. July 2, 2013. doi.org/10.1016/S1474-4422(13)70146-7
Contact: Dr. Patrick Freund
University of Zurich
Interview updated 7/3/2013