Johns Hopkins researchers have demonstrated that a blood test can inform acute spinal cord injury (SCI) diagnosis, prognosis and treatment.

In a recent paper published in the Journal of Clinical Investigation (JCI), Johns Hopkins neurosurgeons showed that levels of cell-free DNA from patient plasma samples correlated with SCI severity. Using machine learning to combine that information with detected alterations in four proteins (FABP3, REST, IL-6 and NF-H), physicians can derive the Spinal Cord Injury Index — a score with high sensitivity and specificity for SCI diagnosis that correlates with injury severity and predicts six-month neurologic improvement.

As the 2024–25 neurosurgery chief resident and first author Tej Azad explains, this index will allow physicians to further classify patients beyond the American Spinal Injury Association Impairment Scale, which denotes SCI as Grade A for the most severe injury.

“There’s a subset of these patients who have a very severe spinal cord injury, but they may have greater recovery potential based on this molecular index,” he says. “One of the really exciting things is that you can begin to substratify these traditional groups, use therapies that may be more beneficial, and for patients who have most severe injury, we can expedite getting them into clinical trials because we know things we have today are probably insufficient.”

Additional authors includes neurosurgeons Nicholas Theodore and Chetan Bettegowda, who is the senior author on the manuscript.

Bettegowda says that advancement in using biomarkers in cancer treatment opened the door to studying conditions such as SCI, which currently has no available biomarkers.

“The study highlights the importance of a multianalyte approach,” he adds. “Combining both DNA and protein-based biomarkers improves the test performance and biological relevance.”

The JCI paper is the first step in developing a concept demonstrated in a January 2024 review article published in the journal Biomarkers. It was also authored by Azad, Theodore and Bettegowda.

The article envisioned a liquid biopsy that would examine cell-free DNA, which can indicate damage to spinal cord neurons via tissue-specific methylation patterns, and proteins and RNA species, which can also reflect neuronal injury.

With only MRI — which is not always possible for severe injuries — and physical examination to rely on, such a test could aid in diagnosis, treatment and monitoring, and in informing prognosis, the researchers say. Monitoring these biomarkers over time could also help physicians determine the effectiveness of different treatments. Azad earned the 2024 Academy Award from the American Academy of Neurological Surgery for the paper.

Having a tool such as this could allow physicians to determine SCIs caused by routine degeneration of the spine that leads to spinal cord compression — which causes the vast majority of SCIs — rather than acute trauma, Theodore says.

“That will change our field fundamentally. I can raise my game here with a blood test and understand, on a molecular level, that a patient may be having a chronic subacute spinal cord injury from a degenerative process,” he says. “Right now, I can examine patients, I can look at MRIs and I can make a decision, and I think we’re pretty good. But the question always is, can we do better? And the answer is: absolutely.”

To contact the Johns Hopkins Neurosurgical Spine Center, call 410-955-4424.