BACKGROUND:
The detection of tissue-specific molecules in blood plays a vital role in the diagnosis and management of acute organ injury. Previous efforts to discover plasma markers of acute ischemic stroke (AIS) have focused on proteins and nucleic acids, but low sensitivity at early time points and poor correlation with injury severity have limited these approaches. We address the hypothesis that the most abundant molecules in the brain, lipids, appear in the plasma earlier after injury and correlate with severity. We focus on a specific lipid subset, sphingolipids (SL), as this subset is highly enriched in the brain compared to plasma.
METHODS:
We performed targeted lipid profiling using SL-specific extraction methods followed by HPLC-MS/MS in plasma collected after acute ischemic stroke in rodents. We validate our findings in a cohort of human patients presenting to the hospital emergently via the CODE STROKE protocol, by comparing SL levels in those ultimately diagnosed as stroke versus mimic. We construct a simple Sphingolipid Score, the summed plasma values of the top two performing SLs in the rodent stroke model, to improve the sensitivity of detection.
RESULTS:
In a rodent model of AIS, plasma collected at 24 hours after the injury revealed a dramatic increase in SL levels in the stroke compared to sham animals. Of the 45 SLs identified, 40 (89%) were elevated, on average 4 fold (max 60 fold). Top two performing species were SM 36:0 and Cer 42:1. Among 14 patients presenting via the CODE STROKE protocol, 8 (57%) were female, median age was 75 (range 41-89), NIHSS 14 (range 3-22), time from symptom onset to blood draw was 388 min (range 80-66). 44% were treated with IV tPA. Final diagnosis was MCA occlusion in 7 (50%), lacunar stroke in 2 (14%), and mimic (migraine, seizure, factitious disorder, Bell’s palsy) in the remainder. In patients with acute stroke, we identify significant increases in Sphingolipid Score for all patients (4.7 vs. 1.9, p<0.05) as well as those with blood draw within three hours of symptom onset (4.6 vs. 1.9, p<0.05). Sphingolipid score correlated linearly with DWI volume over a wide range from 1.5-236 mL (r2=0.7, p<0.05).
CONCLUSIONS:
Targeted lipid profiling may yield clinically relevant plasma markers of acute brain injury.
Multiple Recurrent Acute Ischemic Strokes Treated by Thrombectomy in a Patient with Acute Pulmonary Embolism
