Novel Metabolites as Potential Indicators of Recovery After Large Vessel Occlusion Stroke: A Pilot Study

Introduction: Serum metabolome changes after acute ischemic stroke (AIS), but the significance of this is poorly understood. We evaluated whether this change is associated with AIS outcomes in patients with large vessel occlusion (LVO). To improve validity, we combined cross-sectional and longitudinal designs and analyzed serum using Nuclear Magnetic Resonance (NMR) and Liquid Chromatography-Mass Spectrometry (LC-MS). Methodology: In the cross-sectional part, we compared serum metabolome from 48 LVO strokes, collected at 48-72 h, and analyzed with NMR, while in the longitudinal part, we compared metabolome from 15 LVO strokes, collected at <24 h, 48-72 h, 5-7 days, and 80-120 days, and analyzed with LC-MS between patients with modified Rankin Scores (mRS) of 0-3 and 4-6 at 90 days. We hypothesized that compounds elevated in patients with mRS 0-3 in the cross-sectional part would also be elevated in the longitudinal part, and vice versa. We used regression for the analysis and TSBH for multiple testing. Results: In the cross-sectional part, cholesterol, choline, phosphoglycerides, sphingomyelins, and phosphatidylethanolamines had lower levels in patients with an mRS of 0-3 compared to an mRS of 4-6. In the longitudinal part, lower levels of sphingomyelin (d18:1/19:0, d19:1/18:0)* significantly correlated with an mRS of 0-3 in patients with small infarction volume, while lower levels of sphingolipid N-palmitoyl-sphingosine (d18:1/16:0), 1-palmitoyl-2-docosahexaenoyl-GPC (16:0/22:6), 1-palmitoyl-2-docosahexaenoyl-GPE, palmitoyl-docosahexaenoyl-glycerol (16:0/22:6), campesterol, and 3beta-hydroxy-5-cholestenoate correlated with an mRS of 0-3 in patients with large infarction volume. Conclusions: This pilot study showed that lower levels of lipidomic components nerve cell membrane correlate with good AIS outcomes. If proven on large-scale studies, these compounds may become important AIS outcome markers.