P112. Role of metabolites in bio-fluids as a prognostic indicator of neurological recovery in acute spinal cord injury (ASCI)

Abstract

BACKGROUND CONTEXT Acute spinal cord injury (ASCI) is still having substantial morbidity and mortality despite of advanced therapeutics. Major obstacles are paucity of monitoring tools or biomarkers for severity determination, recovery and prognostication. A prospective case control pilot study with serum 1H NMR spectroscopic metabolic profiling was carried out to evaluate metabolites perturbations and its relationship with recovery and to see role of stem cells in facilitating neurological recovery. PURPOSE A pilot study with serum 1H NMR spectroscopic metabolic profiling was carried out to evaluate metabolites perturbations and its relationship with recovery and to see role of stem cells in facilitating neurological recovery. STUDY DESIGN/SETTING A prospective case control pilot study was conducted in the spinal cord injury (SCI) unit of the Department of Orthopaedic Surgery in collaboration with the Department of Neurology, Department of Biochemistry, King George's Medical University (KGMU), Lucknow and Department of CBMR, Sanjay Gandhi Post Graduate Institute of Medical Science (SGPGIMS), Lucknow from December 2012 to July 2018. PATIENT SAMPLE A total of 135 subjects were enrolled in the study. OUTCOME MEASURES NMR data of serum and urine samples were quantified and subjected to multivariate analysis using supervised OSC-PCA followed by OPLS-DA was performed in the full study. This finding was further validated in the VIP scores. METHODS A prospective case control pilot study total of 135 subjects were enrolled in the study; 65ASCI subjects, divided into two groups. Fixation alone (FA, n= 34). Fixation with stem cells therapy (FST, n= 31). Seventy healthy subjects (HCs) were enrolled. Serum and urine samples were collected at admission (baseline), sixth week, third month and after sixth month (follow-up). RESULTS Gender analysis revealed that 103 out of 135 participants were male. The age group of 18 to 30 years was found most prone to SCI. Fall from height and road traffic accidents were the two most common modes of injuries. Most common injured segments of thoraco-lumbar spine were T10-L2 levels. On AIS grading, highly significant improvement was observed in FST group in comparison to FA group. In FST group, 61.29% subjects remained in AIS A and the percentage improvements to AIS B, C and D were 12.90%, 16.13% and 9.68%, respectively, whereas in FA group these values were 67.65%, 17.64%, 11.76% and 2.94%, respectively. At the sixth month follow-up, improvements in sensory and motor scores were observed in both cases groups (FST and FA), but FST group showed better results. In the spectra of urine biofluid, 43 metabolites were identified and assigned and t28 metabolites were identified and assigned in serum biofluid. Predominantly amino acids and ketone bodies played vital role in the differentiation of groups. An OSC-PCA and OPLS-DA model was created for investigating the role of metabolites in differentiation amid all ASCI subjects against healthy control at baseline as well as at final follow-up. Statistical comparison was validated by OSC-PCA as well as OPLS-DA methods and multivariate data analysis resulted in to R2 value of 0.91 and 0.81 and Q2 value of 0.81 and 0.67, respectively. The generated model was robust enough for evaluating the differentiation among the present data set. The 3D OSC-PCA model generated resulted to the total explained variance of 50.21% and 50.67%, respectively. The 3D scattered score plots represented the shifting of more ASCI subjects towards healthy control in the final follow-up, which is suggestive of improved health status and an indicator of better prognosis in ASCI subjects. CONCLUSIONS Serum and urine NMR spectroscopy reveals certain metabolites perturbations having clear correlation with pattern of recovery in treated ASCI subject. Stem cells treatment group had comparatively effective recovery. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.