Currently, there are no established
biomarkers for diagnosing preclinical vasospasm or monitoring its progression. Two areas of extensive
biomarker research are neuroimaging and
biochemical markers in body fluids, such as cerebrospinal fluid (CSF). We performed a review of studies conducted over the past 2 decades summarizing the science to date and the evolution of CSF
biomarkers in
subarachnoid hemorrhage (SAH). A Medline search performed using the search terms "
subarachnoid hemorrhage marker AND cerebrospinal fluid," limited to the period January 1, 1990 to June 1, 2009, returned 62 references. Abstracts that did not deal primarily with SAH and potential markers in the CSF of humans were excluded, resulting in 27 abstracts. Only articles providing sufficient information for a substantiated analysis were selected. In addition, articles identified in reference lists of individual articles were selected if considered appropriate. Evidence was classified as class I-IV and recommendations were classified as category A-C according to European Federation of Neurological Societies guidelines. We evaluated CSF markers in SAH patients and divided them into 3 categories: A, markers with auspicious value; B, candidate markers; and C, noncandidate markers. Category A markers included
tumor necrosis factor (TNF)-α, soluble
tumor necrosis factor receptor I (sTNFR-I), and
interleukin (IL)-1 receptor antagonist (IL-1ra), as well as the
neurofilament proteins NFL and NfH. Category B markers included
apolipoprotein E (
ApoE),
F2-isoprostane (F2-IsoP), NOx, and the indicators for
thrombin activity membrane-bound
tissue factor (mTF) and
thrombin-antithrombin III complex (TAT) for neurologic outcome prediction, as well as
E-selectin,
lactate, alpha-II
spectrin breakdown products (SBDPs), asymmetric
dimethyl-L-arginine (ADMA), and
monocyte chemoattractant protein-1 (MCP-1) for vasospasm prognostication. Category C markers included S100B,
platelet-derived growth factor (PDGF), YKL-40,
chitotriosidase,
intercellular adhesion molecule-1 (ICAM-1),
vascular cell adhesion molecule-1 (VCAM-1), and
IL-8.
Cytokines and their receptors, as well as neuronal intracellular
proteins, seem to be potential markers for outcome determination in patients after SAH.