Prediction value of genetic and neuromarkers in blood and liquor in patients with severe traumatic brain injury
Year: 2015
Type: dissertation
Study design: Observational Study
Abstract: Background: Severe traumatic brain injury (sTBI) is the most common cause of\nmortality in young adults. sTBI induces variable brain damage, invisible in Computer\nTomographic scans early post-trauma. Further, neurology is difficult to evaluate in\nsedated patients. Therefore, biochemical neuromarkers (BNMs) in blood or\ncerebrospinal fluid (CSF) may be valuable tools to both evaluate trauma and to\nprognosticate patient outcome.\nAims: The aim of the thesis was to evaluate if concentrations of the BNMs; Glial\nFibrillary Acid Protein (GFAP, CSF, study IV), Neurofilament light (NFL, CSF,\nstudy IV), Tau (CSF, study II), β-amyloid (1-42) and amyloid precursor-proteins\n(CSF & plasma, study I) were enhanced after a sTBI. Further, we investigated if\nthese levels were correlated to outcome, neurology and patient ability of daily living\n1-year post-trauma. Finally, we explored if patient-genotype, specifically\nApolipoprotein E, (gene APOE), influenced 1-year outcome in sTBI-patients,\n(plasma, study III).\nMethods: Patients were consecutively included if; aged ≥7 years, < 9 in Glasgow\nComa Scale, receiving an indwelling ventricular catheter allowing CSF sampling),\nwere artificially ventilated and admitted to the Neurointensive care unit (NICU)\nwithin 48h post-trauma. NICU-care was performed according to a standardized\nprotocol. CSF samples were collected on days 0-4, 6, 8 and once on days 11-18.\nSurviving patients were assessed at 1-year evaluating; 1) outcome by Glasgow\nOutcome Scale (GOS), 2. neurology and 3. activities of daily living. NFL, GFAP,\nTau, β-amyloid (1-42) and amyloid precursor-proteins were all analyzed by ELISAmethods.\nAPOE genotyping was performed by polymerase chain reaction & solidphase\nmini-sequencing.\nResults: During the inclusion period, patients (n=28-96) were included into studies IIV\nfor CSF and /or blood sampling. Study I; β-amyloid (1-42) and amyloid\nprecursor-proteins increased from day 0 until day 11 in the CSF, but not in plasma. In\nstudy II we found enhanced levels of CSF-Tau on days 2-3 correlated to mortality\n(GOS 1) at 1-year. In study III we found that patients with APOE allele 4 had worse\noutcome (GOS) at 1-year. Finally, in paper IV we found increased CSF levels of\nGFAP and NFL both correlating to outcome (GOS) at 1-year.\nConclusions; In this thesis we have found in sTBI-patients that genetic and BNMs in\nthe plasma and/or CSF correlate to outcome at 1 -year post-trauma. The result may\nbe clinically applicable to prognosticate outcome and influence treatment paradigms\nin these patients.
Author: Martin Öst
Institution: University of Gothenburg
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1635388739