Changes in the Cerebrospinal Fluid Ceramide Profile After Subarachnoid Hemorrhage

Abstract

The purpose of this study was to investigate changes in the cerebrospinal fluid sphingolipid profile in patients with subarachnoid hemorrhage in relation to the occurrence of symptomatic vasospasm and outcome at hospital discharge. The ceramide profile in the cerebrospinal fluid was determined by mass spectrometry in control subjects and patients with Fisher 3 grade subarachnoid hemorrhage within 48 hours of the bleed. Patients were prospectively followed and subcategorized based on the occurrence of symptomatic vasospasm and modified Rankin Scale at discharge. Compared to control subjects, patients with subarachnoid hemorrhage had higher cerebrospinal fluid levels of total ceramide (12.4±8.8 versus 54.6±49.3 pmol/mL; P<0.001). In the subgroup analysis, total ceramide levels in individuals with symptomatic vasospasm (104.2±57.0 pmol/mL) were higher than in those with asymptomatic vasospasm (32.4±25.7 pmol/mL; P=0.006) and no vasospasm (30.9±15.7 pmol/mL; P=0.003). In addition, compared to patients with a good outcome (modified Rankin Scale ≤3), individuals with poor outcome (modified Rankin Scale ≥4) had higher cerebrospinal fluid levels of total ceramide (79±25 versus 23±6 pmol/mL; P=0.008). When the relative contributions of the different ceramide species were calculated, a higher relative concentration of C(18:0) ceramide was observed in individuals with symptomatic vasospasm (P=0.018) and poor outcome (P=0.028). Ceramide profile changes occur in subarachnoid hemorrhage. In this small case-based series elevation of levels of this sphingolipid, particularly C(18:0), was associated with the occurrence of symptomatic vasospasm and poor neurological outcome after subarachnoid hemorrhage.