The International Spinal Cord Injury Blood Biomarker Longitudinal Evaluation (I-SCRIBBLE) Study

Patients (≥19 years old) with acute blunt non-penetrating traumatic SCI of AIS grade A, B, C, or D will be enrolled at participating sites. The first blood samples will be drawn within 24 hours of injury (the baseline/enrollment visit); afterwards, blood samples are drawn within each successive 24-hour period postinjury until Day 7, and then at 6 months and 12 months postinjury. Blood samples will be drawn from existing lines (eg, arterial line, central venous catheter \[CVC\] lines, and intravenous \[IV\] line) that are inserted as part of standard of care. If an existing line has been discontinued, blood will be drawn via venipuncture.

At each time point, one 15 mL sample of blood will be drawn, which will be divided into: 6 mL for serum, 4 mL for plasma, and 5 mL for RNA isolation (for transcriptomics). At any of these time points, an additional 1 mL blood sample will also be drawn for DNA extraction (for the purpose of ApoE genotyping). The samples will first be processed and temporarily stored by the sites and then sent to the coordinating center at UBC, Vancouver, Canada, for central storage and analyses. Levels of NF-L and GFAP in serum and plasma will be analyzed on the Quanterix Simoa instrument (Lexington, KY, US) for each time point collected to determine the accuracy of these biomarkers to stratify injury severity and to predict outcome.

To the extent that is possible, a full ISNCSCI examination will be completed at enrollment. A motor-only exam of the upper and lower extremities will be completed at Day 4 and Day 7 postinjury. A full ISNCSCI examination will be repeated at 6- and 12-month visits. The Spinal Cord Independence Measure (SCIM) version III will be completed at 6- and 12-month visits to assess functional recovery.

A group of patients who suffer traumatic spinal fracture and/or dislocation of the spinal column but without neurologic injury will be enrolled as non-SCI spine trauma control participants. For these participants, one 15 mL sample of blood (6 mL for serum, 4 mL for plasma, and 5 mL for RNA isolation) will be drawn within 24 hours of injury (Day 1) and either at discharge or at Day 7 postinjury, whichever comes first. No additional follow-ups (FUs) are required for these control participants.

• Accuracy of serum biomarker levels at different time points postinjury for classifying the baseline injury severity, ie, the AIS grade (A, B, C, and D). [Time frame: 1 Day - 12 months]
• Accuracy of serum biomarker levels for predicting other neurologic outcomes at 6 months postinjury [Time frame: 6 months]
• Investigate which time point(s) postinjury is/are the most accurate for classifying the baseline AIS grade and predicting neurologic outcomes at 6 months postinjury [Time frame: 6 months]
• Investigate whether accuracy of classification and prediction of neurologic outcomes at 6 months postinjury can be enhanced by combining serum NF-L and GFAP levels [Time frame: 6 months]
• Investigate whether accuracy of prediction of neurologic outcomes at 6 months postinjury can be enhanced by evaluating the change in serum biomarker levels over time during the first 7 days postinjury. [Time frame: 6 months]
• Investigate the relationship between the accuracy of serum biomarker levels for classification of baseline AIS grade and the perceived reliability of baseline ISNCSCI examination [Time frame: Baseline]
• Determine the accuracy of serum biomarker levels for predicting neurologic outcomes at 12 months postinjury [Time frame: 12 months]
• Determine the accuracy of serum biomarker levels for distinguishing acute traumatic SCI from acute spine trauma without neurologic deficit [Time frame: Baseline]
• Effect of associated trauma on serum biomarker levels [Time frame: Baseline]
• Relationship between serum and plasma levels of the biomarkers [Time frame: 12 months]
• Accuracy of ApoE genotype [Time frame: 6 and 12 months]
• Accuracy of measures of injury severity on baseline MRI [Time frame: 6 and 12 months]