Background: Severe traumatic brain injury (sTBI) is the most common cause of
mortality in young adults. sTBI induces variable brain damage, invisible in Computer
Tomographic scans early post-trauma. Further, neurology is difficult to evaluate in
sedated patients. Therefore, biochemical neuromarkers (BNMs) in blood or
cerebrospinal fluid (CSF) may be valuable tools to both evaluate trauma and to
prognosticate patient outcome.
Aims: The aim of the thesis was to evaluate if concentrations of the BNMs; Glial
Fibrillary Acid Protein (GFAP, CSF, study IV), Neurofilament light (NFL, CSF,
study IV), Tau (CSF, study II), β-amyloid (1-42) and amyloid precursor-proteins
(CSF & plasma, study I) were enhanced after a sTBI. Further, we investigated if
these levels were correlated to outcome, neurology and patient ability of daily living
1-year post-trauma. Finally, we explored if patient-genotype, specifically
Apolipoprotein E, (gene APOE), influenced 1-year outcome in sTBI-patients,
(plasma, study III).
Methods: Patients were consecutively included if; aged ≥7 years, < 9 in Glasgow
Coma Scale, receiving an indwelling ventricular catheter allowing CSF sampling),
were artificially ventilated and admitted to the Neurointensive care unit (NICU)
within 48h post-trauma. NICU-care was performed according to a standardized
protocol. CSF samples were collected on days 0-4, 6, 8 and once on days 11-18.
Surviving patients were assessed at 1-year evaluating; 1) outcome by Glasgow
Outcome Scale (GOS), 2. neurology and 3. activities of daily living. NFL, GFAP,
Tau, β-amyloid (1-42) and amyloid precursor-proteins were all analyzed by ELISAmethods.
APOE genotyping was performed by polymerase chain reaction & solidphase
mini-sequencing.
Results: During the inclusion period, patients (n=28-96) were included into studies IIV
for CSF and /or blood sampling. Study I; β-amyloid (1-42) and amyloid
precursor-proteins increased from day 0 until day 11 in the CSF, but not in plasma. In
study II we found enhanced levels of CSF-Tau on days 2-3 correlated to mortality
(GOS 1) at 1-year. In study III we found that patients with APOE allele 4 had worse
outcome (GOS) at 1-year. Finally, in paper IV we found increased CSF levels of
GFAP and NFL both correlating to outcome (GOS) at 1-year.
Conclusions; In this thesis we have found in sTBI-patients that genetic and BNMs in
the plasma and/or CSF correlate to outcome at 1 -year post-trauma. The result may
be clinically applicable to prognosticate outcome and influence treatment paradigms
in these patients