A Preliminary Cohort Study Assessing Routine Blood Analyte Levels and Neurological Outcome after Spinal Cord Injury

Abstract

There is increasing interest in the identification of biomarkers that could predict neurological outcome following a spinal cord injury (SCI). Although initial American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade is a good indicator of neurological outcome, for the patient and clinicians, an element of uncertainty remains. This preliminary study aimed to assess the additive potential of routine blood analytes following principal component analysis (PCA) to develop prognostic models for neurological outcome following SCI. Routine blood and clinical data were collected from SCI patients (n = 82) and PCA used to reduce the number of blood analytes into related factors. Outcome neurology was obtained from AIS scores at 3 and 12 months post-injury, with motor (AIS and total including all myotomes) and sensory (AIS, touch and pain) abilities being assessed individually. Multiple regression models were created for all outcome measures. Blood analytes relating to ''liver function'' and ''acute inflammation and liver function'' factors were found to significantly increase prediction of neurological outcome at both 3 months (touch, pain, and AIS sensory) and at 1 year (pain, R 2 increased by 0.025 and total motor, R 2 increased by 0.016). For some models ''liver function'' and ''acute inflammation and liver function'' factors were both significantly predictive, with the greatest combined R 2 improvement of 0.043 occurring for 3 month pain prediction. These preliminary findings support ongoing research into the use of routine blood analytes in the prediction of neurological outcome in SCI patients.

Routinely Measured Hematological Markers Can Help to Predict American Spinal Injury Association Impairment Scale Scores after Spinal Cord Injury

“…We previously published a preliminary study that highlighted the value of routinely measured blood analytes in prognostic models of SCI, and demonstrated that some blood measures, particularly markers of liver function, added modest but statistically significant value to predictions of 3- and 12-month ISNSCI AIS motor and sensory scores. 23 In this study, we have validated our findings in another, independent and larger SCI cohort. We have further developed alternative, more robust methods of modeling and have demonstrated that similar markers, including alanine transaminase (ALT) and gamma-glutamyl transferase (GGT) add value not only when predicting AIS scores at discharge and 12 months, but also with regard to Spinal Cord Independence Measure (SCIM) outcomes.…”

“…Two factors—“liver function,” consisting of alanine transaminase, alkaline phosphatase and GGT, and “liver function and inflammation,” consisting of CRP and total bilirubin—added statistically significant value to models of AIS touch and pain scores at 3 months post-injury, and AIS motor and pain scores at 12 months. 23 , 61 , 62 Total bilirubin in particular was included in five of eight penalized models and was significant in three of the non-penalized models. This provides further evidence that liver function is relevant to neurological recovery in SCI.…”

“…The results from this study suggest that routinely measured blood analytes can provide useful prognostic information for AIS scores and SCIM assessments up to 12 months post-injury, reinforcing the findings of our preliminary study. 23 Markers of liver function are of particular interest, and rehabilitation clinicians should consider the maintenance of liver health as a priority as it may be relevant to neurologic functional recovery. More research is needed to establish whether or not the relationship between SCI recovery and liver function is causal.…”

Liver inflammation before spinal cord injury worsens neuropathology, hepatic injury, metabolic syndrome and locomotor deficits

“…Here we show that perturbing the spinal cord-liver axis also damages the spinal cord and, depending on the severity of liver inflammation at the time of SCI, may even be detrimental to the brain. Notably, a clinical study of SCI subjects showed that blood analytes relating to “liver function” and “acute inflammation and liver function” including ALT were excellent predictors of neurological function at 3 and 12 months post-SCI (Brown et al ., 2020). This suggests that liver pathology after SCI is an important biomarker and imply a two-way link between hepatic inflammation/injury and the outcome from SCI.…”

“…As stated above, liver inflammation may be an important biomarker for SCI severity (Brown et al ., 2020). Our prior preclinical work shows that the liver is not only a “reporter” of injury but that the liver itself is also a “victim” of SCI, as it develops robust and persistent inflammation and lipid accumulation consistent with development of “neurogenic” NASH (Sauerbeck et al ., 2015; Goodus et al ., 2018; Goodus and McTigue, 2020).…”