“We’ve always been limited in predicting recovery in these patients,” Pfyffer said.

The research team realized that better evidence of recovery might be in plain sight, in the MRI scans typically performed in such cases.

“MRI scans are often performed after a spinal cord injury, but usually to view the damage and guide surgery, not to predict outcome,” Pfyffer said.

The researchers knew that MRI scans could not only reveal the damage, but also the remaining spinal cord tissue around the site of the injury, called tissue bridges.

“We can get a measure of how much spinal cord tissue is spared and functional and still transmitting information from the spinal cord to the brain and back,” Pfyffer said. “The more tissue that’s spared, the better we would expect the recovery to be.”

Predicting recovery

In the new study, researchers retrospectively analyzed data from 227 patients admitted to three hospitals in Denver, Colorado; Murnau, Germany; and Zurich, Switzerland. The patients had cervical spinal cord injuries and no other neurological or psychiatric conditions.

Because the researchers wanted to investigate spontaneous recovery, they included only patients who were not participating in clinical trials and who received only conventional care.

They measured the width of the tissue bridges on MRI scans taken three to four weeks after the injury, when the spinal cord has stabilized and any initial swelling has subsided.

When they compared the width of the tissue bridges to the patients’ sensorimotor test scores upon admission to the hospital and upon discharge three months later, they found a clear pattern. Based on this data, they developed a statistical model that could predict how many points a patient would likely score on specific sensorimotor tests. The model took into account the patient’s age, gender, location of the injury, and baseline test scores, as well as differences between hospitals.

Tissue bridges have given our models much more predictive power. In some ways they outperform models that only take clinical factors into account.

For example, for every millimeter of tissue bridge width preserved, a patient would gain 5.9 points (out of 100) on their motor score and 6.4 points (out of 112) on their light touch score after three months.

The patients in Germany and Switzerland were followed for 12 months, allowing researchers to examine more long-term trends. In general, they found that patients experienced most of their recovery within the first three months.

Sorting patients

Promising experimental therapies for spinal cord injuries include electrical stimulation and antibody treatments that stimulate nerve regeneration, but a pressing problem in getting clinical trials off the ground is not knowing whether and to what extent some patients will recover on their own. Grouping patients with similar potential for recovery would increase the efficiency of clinical trials, requiring fewer patients to achieve statistical validity.

The new research shows that tissue bridges significantly improve the ability to classify patients into groups with a similar prognosis.

“What was most surprising is that tissue bridges added so much predictive power to our models — in some ways they outperformed models that included only clinical factors,” Pfyffer said.

Models that combined tissue bridge measurements with clinical assessments achieved the most consistent sorting results across all three centers. And consistent results across datasets is the goal, Pfyffer said.

“You don’t want to see differences in prediction because that would mean the study results can’t be replicated between centers,” he said.

Nothing special

The researchers are now working on ways to further improve the prognosis with tissue bridges. They are applying machine learning to make more objective measurements with MRI scans and to use additional scans to measure all dimensions of the spared tissue. This would allow them to identify the specific pathways of the spinal cord, innervating individual parts of the body, that remain viable.

But the benefits of tissue bridge measurements are already accessible in most hospitals that treat spinal cord injuries. “We’ve gotten these measurements from conventional MRI scans that are done in many centers, so these are not expensive MRI scans that take a lot of time,” Pfyffer said. “It’s pretty easy to get that information.”

Researchers from Craig Hospital, University of Colorado School of Medicine, BG Trauma Center Murnau, Balgrist University Hospital, University of College London and The Ohio State University contributed to the work.

The research received funding from Wings for Life, Austria; the International Foundation for Research in Paraplegia; the EU project Horizon 2020; and the ERA-NET NEURON framework.