title: Evidence that a panel of neurodegeneration biomarkers predicts vasospasm, infarction, and outcome in aneurysmal subarachnoid hemorrhage.
abstract: Biomarkers for neurodegeneration could be early prognostic measures of brain damage and dysfunction in aneurysmal subarachnoid hemorrhage (aSAH) with clinical and medical applications. Recently, we developed a new panel of neurodegeneration biomarkers, and report here on their relationships with pathophysiological complications and outcomes following severe aSAH. Fourteen patients provided serial cerebrospinal fluid samples for up to 10 days and were evaluated by ultrasonography, angiography, magnetic resonance imaging, and clinical examination. Functional outcomes were assessed at hospital discharge and 6-9 months thereafter. Eight biomarkers for acute brain damage were quantified: calpain-derived α-spectrin N- and C-terminal fragments (CCSntf and CCSctf), hypophosphorylated neurofilament H,14-3-3 β and ζ, ubiquitin C-terminal hydrolase L1, neuron-specific enolase, and S100β. All 8 biomarkers rose up to 100-fold in a subset of patients. Better than any single biomarker, a set of 6 correlated significantly with cerebral vasospasm, brain infarction, and poor outcome. Furthermore, CSF levels of 14-3-3β, CCSntf, and NSE were early predictors of subsequent moderate-to-severe vasospasm. These data provide evidence that a panel of neurodegeneration biomarkers may predict lasting brain dysfunction and the pathophysiological processes that lead to it following aSAH. The panel may be valuable as surrogate endpoints for controlled clinical evaluation of treatment interventions and for guiding aSAH patient care.
authors.affiliation: Department of Neurosurgery, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America. siman@mail.med.upenn.edu
authors.forename: Robert
authors.initials: R
authors.lastname: Siman
authors.forename: Nicholas
authors.initials: N
authors.lastname: Giovannone
authors.forename: Nikhil
authors.initials: N
authors.lastname: Toraskar
authors.forename: Suzanne
authors.initials: S
authors.lastname: Frangos
authors.forename: Sherman C
authors.initials: SC
authors.lastname: Stein
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Levine
authors.forename: Monisha A
authors.initials: MA
authors.lastname: Kumar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000134:cerebrospinal fluid; D020520:Brain Infarction / Q000134:cerebrospinal fluid / Q000150:complications*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000134:cerebrospinal fluid / Q000150:complications*; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid / Q000150:complications* / Q000473:pathology / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome; D020301:Vasospasm, Intracranial / Q000134:cerebrospinal fluid / Q000150:complications*; D055815:Young Adult
chemical_list: D015415:Biomarkers