Here’s a look at a paper that came out a few days ago in Lancet Neurology
, “MRI investigation of the sensorimotor cortex and the corticospinal tract after acute spinal cord injury: a prospective longitudinal study
.” Sounds complicated but it means using MRI scans to see what’s going on with the cord itself in the area above the injury.
This work is from a joint research effort between the University of Zurich, University Hospital Balgrist, and University College London.
The headlines picked up in my SCI research filters set this up as breaking news: Damage from SCI causes irreversible tissue loss within 40 days of injury
– much less time than most scientists thought. But don’t get stuck on the ominous tone of irreversibility. It’s not only about the size or timing of the damage – although they do point out that earlier degeneration means poorer outcome. In the broader picture, the research hopes to address the timing of interventions to arrest and perhaps repair the damage.
Says the paper, “Structural volumetric and microstructural MRI protocols remote from the site of spinal cord injury could serve as neuroimaging biomarkers in acute spinal cord injury.”
Translation: The idea is to establish what they call biomarkers – measurable changes in the degeneration of the spinal cord, detected by MRI.
Image on right shows MRI protocol. Red: This shows dynamic tissue loss in the corticospinal tract and sensorimotor cortex after twelve months of spinal cord injury. Green: These are spots with reduced myelin layer.
Credit: Picture: UZH
From the abstact:
In our prospective longitudinal study, we enrolled patients with acute traumatic spinal cord injury and healthy controls. We assessed patients  clinically and by MRI at baseline, 2 months, 6 months, and 12 months, and controls  by MRI at the same timepoints. We assessed atrophy in white matter in the cranial corticospinal tracts and grey matter in sensorimotor cortices by tensor-based analyses of T1-weighted MRI data. We used cross-sectional spinal cord area measurements to assess atrophy at cervical level C2/C3. We used myelin-sensitive magnetisation transfer (MT) and longitudinal relaxation rate (R1) maps to assess microstructural changes associated with myelin. We also assessed associations between MRI parameters and clinical improvement.
The extent of degeneration does coincide with the clinical outcome. “Patients with a greater tissue loss above the injury site recovered less effectively than those with less changes,” said Patrick Freund, the main author of the study at the Paraplegic Center Balgrist.
What they found: degeneration, and earlier than expected. What does this mean? A commentary to the journal article, “Will imaging biomarkers transform spinal cord injury trials
?,” was published simultaneously, co-authored by Canadian neurosurgeon and scientist Michael Fehlings
(a principal investigator in Reeve’s North American Clinical Trials Network - NACTN). It helps frame the Lancet study.
Fehlings is stoked about the emergence of better tools to assess damage, and to use biomarkers as “surrogates” to assess effectiveness of therapies.
From his comment:
An alternative strategy for assessment of patients is to use a surrogate endpoint that shows changes in the intended target of new therapeutic agents. The work presented by Patrick Freund and colleagues in this issue of The Lancet Neurology provides a clever example of an imaging biomarker that could be used as a surrogate for clinical examination. Use of such a technique in the context of a therapeutic intervention would reduce the reliance on broad classification schemes and offer the prospect of less expensive and more efficient clinical trials than we have at present.
…. Imaging biomarkers can potentially be used at any stage of spinal cord injury, from acute to subacute to chronic dependent on the intended target of the therapeutic intervention. Furthermore, they are capable of targeting a multitude of substrates within the CNS, from motor to sensory to autonomic pathways.
…. As discussed by many leading authors in the specialty, an individual therapeutic strategy is unlikely to serve as the magic bullet for restoration of function after injury. Rather, a combination of strategies at different timepoints is probably needed—for example, the use of neuroprotective strategies during the acute phase followed by neuroregenerative therapies in later stages of recovery, after hostile, secondary injury mechanisms have subsided. Through a combination of treatment strategies and adoption of imaging biomarkers, the next generation of clinical trials will have the potential to personalise the care of patients with spinal cord injury.
"This study is an excellent example of the value of combining the complementary expertise of the two universities," said Alan Thompson, one of the senior authors of the paper. "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."