| 1. |
- Andersson, Emma, et al.
(författare)
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A prospective outcome study observing patients with severe traumatic brain injury over 10-15 years
- 2017
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 61:5, s. 502-512
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Tidskriftsartikel (refereegranskat)abstract
- Background: Severe traumatic brain injury (sTBI) can be divided into primary and secondary injuries. Intensive care protocols focus on preventing secondary injuries. This prospective cohort study was initiated to investigate outcome, including mortality, in patients treated according to the Lund Concept after a sTBI covering 10-15 years post-trauma. Methods: Patients were included during 2000-2004 when admitted to the neurointensive care unit, Sahlgrenska University Hospital. Inclusion criteria were: Glasgow coma scale score of 8, need for artificial ventilation and intracranial monitoring. Glasgow Outcome Scale (GOS) was used to evaluate outcome both at 1-year and 10-15 years post-trauma. Results: Ninety-five patients, (27 female and 68 male), were initially included. Both improvement and deterioration were noted between 1- and 10-15 years post-injury. Mortality rate (34/95) was higher in the studied population vs. a matched Swedish population, (Standard mortality rate (SMR) 9.5; P < 0.0001). When dividing the cohort into Good (GOS 4-5) and Poor (GOS 2-3) outcome at 1-year, only patients with Poor outcome had a higher mortality rate than the matched population (SMR 7.3; P < 0.0001). Further, good outcome (high GOS) at 1-year was associated with high GOS 10-15 years post-trauma (P < 0.0001). Finally, a majority of patients demonstrated symptoms of mental fatigue. Conclusion: This indicates that patients with severe traumatic brain injury with Good outcome at 1-year have similar survival probability as a matched Swedish population and that high Glasgow outcome scale at 1-year is related to good long-term outcome. Our results further emphasise the advantage of the Lund concept.
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| 2. |
- Andersson, Emma, et al.
(författare)
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Acute-Phase Neurofilament Light and Glial Fibrillary Acidic Proteins in Cerebrospinal Fluid Predict Long-Term Outcome After Severe Traumatic Brain Injury
- 2024
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Ingår i: NEUROCRITICAL CARE. - 1541-6933 .- 1556-0961.
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Tidskriftsartikel (refereegranskat)abstract
- Background This study investigated trajectory profiles and the association of concentrations of the biomarkers neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in ventricular cerebrospinal fluid (CSF) with clinical outcome at 1 year and 10-15 years after a severe traumatic brain injury (sTBI).Methods This study included patients with sTBI at the Neurointensive Care Unit at Sahlgrenska University Hospital, Gothenburg, Sweden. The injury was regarded as severe if patients had a Glasgow Coma Scale <= 8 corresponding to Reaction Level Scale >= 4. CSF was collected from a ventricular catheter during a 2-week period. Concentrations of NfL and GFAP in CSF were analyzed with enzyme-linked immunosorbent assay. The Glasgow Outcome Scale (GOS) was used to assess the 1-year and 10-15-year outcomes. After adjustment for age and previous neurological diseases, logistic regression was performed for the outcomes GOS 1 (dead) or GOS 2-5 (alive) and GOS 1-3 (poor) or GOS 4-5 (good) versus the independent continuous variables (NfL and GFAP).Results Fifty-three patients with sTBI were investigated; forty-seven adults are presented in the article, and six children (aged 7-18 years) are described in Supplement 1. The CSF concentrations of NfL gradually increased over 2 weeks post trauma, whereas GFAP concentrations peaked on days 3-4. Increasing NfL and GFAP CSF concentrations increased the odds of GOS 1-3 outcome 1 year after trauma (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.07-2.80, p = 0.025; and OR 1.61, 95% CI 1.09-2.37, p = 0.016, respectively). Similarly, increasing CSF concentrations of NfL and GFAP increased the odds for GOS 1-3 outcome 10-15 years after trauma (OR 2.04, 95% CI 1.05-3.96, p = 0.035; and OR 1.60, 95% CI 1.02-2.00, p = 0.040).Conclusions This study shows that initial high concentrations of NfL and GFAP in CSF are both associated with higher odds for GOS 1-3 outcome 1 year and 10-15 years after an sTBI, implicating its potential usage as a prognostic marker in the future.
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| 3. |
- Csajbok, Ludvig Z, 1964, et al.
(författare)
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Apolipoprotein E polymorphism in aneurysmal subarachnoid haemorrhage in West Sweden.
- 2016
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Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 133:6, s. 466-474
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Tidskriftsartikel (refereegranskat)abstract
- Aneurysmal subarachnoid haemorrhage (aSAH) is associated with high morbidity and mortality despite novel treatments. Genetic variability may explain outcome differences. Apolipoprotein E (ApoE) is a glycoprotein with a major role in brain lipoprotein metabolism. It has three isoforms encoded by distinct alleles: APOEε2, APOEε3 and APOEε4. The APOEε4 allele is associated with Alzheimer's disease and worse outcome after traumatic brain injury and ischaemic stroke. This prospective blinded study explored the influence of the APOEε4 polymorphism on the risk of aSAH, risk of cerebral vasospasm (CVS) and 1-year neurological outcome.
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| 4. |
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| 5. |
- Nylén, Karin, 1961, et al.
(författare)
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CSF -neurofilament correlates with outcome after aneurysmal subarachnoid hemorrhage.
- 2006
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Ingår i: Neurosci Lett. - : Elsevier BV. - 0304-3940. ; 404:1-2, s. 132-6
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Tidskriftsartikel (refereegranskat)abstract
- Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating event. Following the bleeding, a number of pathophysiological changes and clinical factors determine outcome. Not surprisingly, attempts to predict outcome based on a single factor have failed. The neurological status graded at admission to hospital and distributions of the blood on CT are the strongest predictors. There is evidence that cerebrospinal fluid (CSF) proteins may serve as markers of the extent of brain damage. The present study is focused on the light unit of neurofilament protein (NFL), previously not evaluated in aSAH. Lumbar puncture (LP), neurological grading according to World Federation of Neurological Surgeons (WFNS) and neurological examination according to the National Institute of Health Stroke Scale (NIHSS) were performed in 48 consecutive patients with aSAH 10-14 days after the hemorrhage. CSF-NFL concentrations were analyzed using an ELISA. Outcome was assessed after 1 year and categorised according to the extended Glasgow Outcome Scale (GOSE). A significant correlation between CSF-NFL and GOSE was detected at follow up after 1 year. CSF-NFL also correlated with WFNS and NIHSS on the day of the lumbar puncture. CSF-NFL is a biochemical marker of brain damage correlating to neurological status and long-term outcome after aneurysmal subarachnoid hemorrhage.
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| 6. |
- Nylen, K, et al.
(författare)
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Increased serum-GFAP in patients with severe traumatic brain injury is related to outcome
- 2006
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Ingår i: J Neurol Sci. - : Elsevier BV. - 0022-510X. ; 240:1-2, s. 85-91
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Several studies have established the relevance of S-100 in blood as a marker of brain damage after traumatic brain injury. However, a more specific marker is required and glial fibrillary acidic protein (GFAP) is considered to be a good candidate. METHODS: In order to assess the increase of GFAP in serum (s-GFAP) after a severe traumatic brain injury (TBI) we collected daily serum samples from 59 patients with severe TBI starting on the day of the trauma. S-GFAP was measured using a sandwich ELISA. The Glasgow outcome scale (GOS) assessed outcome after 1 year. RESULTS: All but one patient had maximal s-GFAP values above the laboratory reference value (median increased 10-fold). The highest detected levels were seen during the first days after TBI and then decreased gradually. Patients with unfavourable outcome had significantly (p<0.001) higher maximal s-GFAP values in the acute phase compared with patients with favourable outcome. All patients (n=5) with s-GFAP>15.04 microg /L died (reference level<0.15 microg/L). We found no significant difference in the maximal s-GFAP levels of patients with isolated brain injury in comparison with patients with multiple traumas. CONCLUSION: Serum-GFAP is increased during the first days after a severe traumatic brain injury and related to clinical outcome.
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| 7. |
- Nylén, Karin, 1961, et al.
(författare)
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Serum glial fibrillary acidic protein is related to focal brain injury and outcome after aneurysmal subarachnoid hemorrhage.
- 2007
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Ingår i: Stroke. - 1524-4628. ; 38:5, s. 1489-94
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Aneurysmal subarachnoid hemorrhage (aSAH) stands out from other subtypes of stroke because of the high early mortality and the risk of complications. Serum glial fibrillary acidic protein (s-GFAP) concentrations are increased after stroke. The aim of this study was to investigate whether s-GFAP could be used as a marker of brain damage and outcome after aSAH. METHODS: Serum samples were obtained on a regular basis from 116 adults during a 2-week period after aSAH and analyzed using an enzyme-linked immunosorbent assay. The World Federation of Neurological Surgeons scale was used for neurological evaluation. Outcome was assessed after 1 year and categorized according to the Extended Glasgow Outcome Scale. RESULTS: Increased s-GFAP levels were seen in 81 of the 116 patients. Maximum s-GFAP correlated with World Federation of Neurological Surgeons scale on arrival and on days 10 to 15 (r=0.37, P<0.001 and r=0.47, P<0.001, respectively). Furthermore, maximum s-GFAP levels were increased in the patient group with radiological signs of focal lesions acute or at 1 year, compared with the group without focal lesions (P<0.001 in both comparisons). Patients with secondary events (re-bleeding or ischemia) reached maximum levels later in the series and both maximum and final s-GFAP levels increased compared with the levels in patients without secondary events (P<0.001 in all 3 comparisons). Finally, maximum s-GFAP correlated with outcome (r=-0.48, P<0.001) and s-GFAP was an independent predictor of dichotomized outcome. CONCLUSIONS: s-GFAP provides information about brain injury severity and outcome after aSAH, which can be useful as a complement to clinical data.
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| 8. |
- Nylén, Karin, 1961, et al.
(författare)
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Serum levels of S100B, S100A1B and S100BB are all related to outcome after severe traumatic brain injury.
- 2008
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Ingår i: Acta neurochirurgica. - : Springer Science and Business Media LLC. - 0942-0940 .- 0001-6268. ; 150:3
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: S100B is an established marker of brain damage. Used in the context as a biochemical marker, S100B denotes a measurement of all S100 proteins, including at least one S100B monomer, i.e. the sum of the two dimers S100A1B and S100BB. Almost all published studies are based on this "sum concentration". However, the brain specificity of S100B has been questioned and increased serum levels have also been reported after trauma without head injury. Since the S100B monomer dominates in the brain, we hypothesised that the S100BB dimer should be better related to outcome after severe traumatic brain injury than S100A1B or the "sum concentration". METHODS: Daily serum samples were collected from 59 patients with severe traumatic brain injury. Three different ELISA methods were used for measurements of S100B, S100A1B and S100BB respectively. Outcome was assessed after one year and categorised according to the Glasgow Outcome Scale. RESULTS: Serum levels of S100B, S100A1B and S100BB followed the same temporal course, with early maximum and rapidly decreasing values over the first days after the trauma. Maximum serum concentrations of each of the parameters were increased in the patient group with an unfavourable outcome compared with those with a favourable outcome (p = 0.01, 0.006 and 0.004, respectively). CONCLUSION: Both S100A1B and S100BB were related to outcome after severe traumatic brain injury. Even though this study is small, it seems unlikely that separate analyses of the dimers are of any advantage compared with measuring S100B alone.
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| 9. |
- Olsson, Annika, et al.
(författare)
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Marked increase of beta-amyloid(1-42) and amyloid precursor protein in ventricular cerebrospinal fluid after severe traumatic brain injury.
- 2004
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Ingår i: Journal of neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 251:7, s. 870-6
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Tidskriftsartikel (refereegranskat)abstract
- Severe traumatic brain injury (TBI) may result in widespread damage to axons, termed diffuse axonal injury. Alzheimer's disease (AD) is characterised by synaptic and axonal degeneration together with senile plaques (SP). SP are mainly composed of aggregated beta-amyloid (Abeta), which are peptides derived from the amyloid precursor protein (APP). Apart from TBI in itself being considered a risk factor for AD, severe head injury seems to initiate a cascade of molecular events that are also associated with AD. We have therefore analysed the 42 amino acid forms of Abeta (Abeta1-42) and two soluble forms of APP (alpha-sAPP and ss-sAPP) in ventricular cerebrospinal fluid (VCSF) and Abeta(1-42) in plasma from 28 patients in a serial samples 0-11 days after TBI. The levels of alpha-sAPP, ss-sAPP and Abeta(1-42) were determined using ELISA assays. After TBI, there was a significant stepwise increase in VCSF-Abeta(1-42) up to 1173 % from day 0-1 to day 5-6 and in VCSF-beta-sAPP up to 2033 % increase from day 0-1 to day 7-11. There was also a slight but significant increase of VCSF-beta-sAPP from day 0-1 to day 5-6 and day 7-11. By contrast, the plasma- Abeta(1-42) level is unchanged after injury. The marked increase in VCSFAbeta(1-42) implies that increased Abeta expression may occur as a secondary phenomenon after TBI with axonal damage. The unchanged level of plasma-Abeta(1-42) in contrast to the marked increase in VCSF-Abeta(1-42) after severe TBI, supports the suggestion that plasma Abeta(1-42) does not reflect Abeta metabolism in the central nervous system (CNS).
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| 10. |
- Shahim, Pashtun, 1984, et al.
(författare)
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Serum neurofilament light protein predicts clinical outcome in traumatic brain injury
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Axonal white matter injury is believed to be a major determinant of adverse outcomes following traumatic brain injury (TBI). We hypothesized that measurement of neurofilament light protein (NF-L), a protein found in long white-matter axons, in blood samples, may serve as a suitable biomarker for neuronal damage in TBI patients. To test our hypotheses, we designed a study in two parts: i) we developed an immunoassay based on Single molecule array technology for quantification of NF-L in blood, and ii) in a proof-of-concept study, we tested our newly developed method on serial serum samples from severe TBI (sTBI) patients (n = 72) and controls (n = 35). We also compared the diagnostic and prognostic utility of NF-L with the established blood biomarker S100B. NF-L levels were markedly increased in sTBI patients compared with controls. NF-L at admission yielded an AUC of 0.99 to detect TBI versus controls (AUC 0.96 for S100B), and increased to 1.00 at day 12 (0.65 for S100B). Importantly, initial NF-L levels predicted poor 12-month clinical outcome. In contrast, S100B was not related to outcome. Taken together, our data suggests that measurement of serum NF-L may be useful to assess the severity of neuronal injury following sTBI.
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| 11. |
- Waldeck, Peter, 1963, et al.
(författare)
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Brood parasitism in a population of common eider (Somateria mollissima)
- 2004
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Ingår i: Behaviour. - : Brill. - 0005-7959 .- 1568-539X. ; 141, s. 725-739
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Tidskriftsartikel (refereegranskat)abstract
- The common eider differs from many other ducks in being a colonial 'capital' breeder, producing eggs from stored resources. These traits are expected to influence the occurrence of conspecific brood parasitism (CBP), which is particularly common in waterfowl. We analysed CBP in an eider population in the central Baltic Sea 2001-2002, using non-destructive egg albumen sampling combined with protein fingerprinting. This technique greatly increases the detection of parasitic eggs compared to more traditional methods. Parasitic eggs occurred in 20-22% of 164 nests studied, 6% of 754 eggs being laid by other than the host female. Parasitism increased with nest density, was rather evenly distributed over the laying season, and occurred both early and late in the laying sequence of the host. Protein fingerprinting showed that host females laid up to seven eggs, more than previously reported. Among 33 parasitised nests 22 had one parasitic egg, nine had two and two had three. In all but one case all parasitic eggs within a nest were laid by the same female. Although colonial breeding facilitates CBP, it is less frequent in this eider population than in several other diving ducks. Possible contributing reasons are the relatively small clutch size and start of incubation after egg 2 or 3, limiting the time window for successful parasitism.
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| 12. |
- Öst, Martin, 1967, et al.
(författare)
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Apolipoprotein E polymorphism and gender difference in outcome after severe traumatic brain injury.
- 2008
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Ingår i: Acta anaesthesiologica Scandinavica. - : Wiley. - 1399-6576 .- 0001-5172. ; 52:10, s. 1364-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Traumatic brain injury (TBI) is one of the most common causes of death and dismal outcome among children and young adults. The morbidity and mortality differ but more aggressive monitoring and more designated neuro intensive care units have improved the results. Studies have demonstrated a connection between apolipoprotein E (APOE) genotype and outcome after TBI, but few are prospective and none is from northern Europe. APOE has three alleles: epsilon2, epsilon3 and epsilon4. METHODS: A total of 96 patients with Glasgow coma score (GCS) < or =8 were prospectively and consecutively included. APOE genotypes were all analyzed at the same laboratory from blood samples by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: All patients were assessed at 1 year with Glasgow outcome scale extended (GOSE), National Institute of Health Stroke Scale (NIHSS) and the Barthel daily living index. The genotype was available in all patients. Twenty-six patients expressed APOE epsilon4 while 70 patients did not. Outcome demonstrated that patients with APOE epsilon4 had worse outcome vs. those lacking this allele. When subdividing patients into gender, males with APOE epsilon4 did worse, a difference not detected among female patients. CONCLUSIONS: APOE epsilon4 correlated to worse outcome in TBI patients. We also found that males with APOE epsilon4 had poor outcome while females did not. Thus, the results indicate that genetic polymorphism may influence outcome after TBI.
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| 13. |
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| 14. |
- Öst, Martin, 1967
(författare)
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Prediction value of genetic and neuromarkers in blood and liquor in patients with severe traumatic brain injury
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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