Table 4.

Genetic, non-CNS, and Extracellular Biomarkers

Biomarker	Sample source	Observations
Apolipoprotein E (ApoE4)	Blood	Presence of ApoE4 is associated with DIND [53] and unfavorable outcome [53–55] ApoE ε2- or ε4-containing genotypes are not associated with SAH outcome or cerebral infarction [56]
Haptoglobin (Hp) genotype	Blood	Presence of Hp2–2 phenotype is an independent risk factor for focal and global cerebral vasospasm and for poor functional outcome and mortality following SAH [57, 58]
Ryanodine receptor 1 gene (RYR1)	Blood	RYR1 genotype is associated with increased risk of symptomatic vasospasm [67]
Circulating microRNA	Serum	miR-4532, miR-4463, miR-1290, and miR-4793 differentiate SAH patients with DCI from those without DCI [69]
Cardiac Troponin I (cTI)	Serum	Elevated cTI is associated with death [59, 60] Peak cTI is independently predictive of death or severe disability at hospital discharge but not predictive of 3-month mRS [61, 62] Peak cTI and GCS on presentation independently predict in-hospital mortality [63]
B-type Natriuretic Peptide (BNP)	Plasma	BNP > 600 pg/mL is associated with death [59] BNP measured once after SAH (mean 5.5 ± 3.0 days) Top quartile is associated with increased odds of cerebral infarction, particularly in patients without angiographic vasospasm [66]
Glucose, lactate, lactate/pyruvate ratio (L/P ratio), glycerol	Extracellular fluid (ECF)	Lactate, L/P, and glycerol are higher in high-grade SAH [79] L/P independently predict 6- or 12-month outcome [73, 79] High L/P and low glucose are associated with neurological deficits [73] and cerebral infarction [77] “Ischemic pattern” (lactate/glucose and L/P > 20%, 20% increase in glycerol) is present in 17 of 18 patients with DIND [74] Lactate > 4 mM and glutamate > 3 mM for at least 6 consecutive hours are associated with neurological deterioration/DIND [75]

DCI delayed cerebral ischemia, DIND delayed ischemic neurological deficit, ECF extracellular fluid, GCS Glasgow Coma Scale, SAH subarachnoid hemorrhage