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The association of ICP, CPP, CT findings and the levels of S-100B and NSE in severe traumatic head injury. Prognostic value of the biomarkers.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

The first hypothesis was that biochemical markers of brain injury might be influenced by the intracranial pressure (ICP) and cerebral perfusion pressure (CPP) after severe traumatic brain injury (sTBI), in patients treated by an ICP targeted therapy. A second hypothesis was that there is a relationship between the biomarker levels and a systematic classification of the CT-scan of the brain. We also hypothesized that clinical outcome can be related to biomarker levels and that mortality may be predicted by the biomarkers. In this prospective consecutive study patients with sTBI were included. Inclusion criteria were Glasgow Coma Scale (GCS) score ≤ 8, age between 15 and 70 years, an initial cerebral perfusion pressure >10 mm Hg. Blood samples for neuron specific enolase (NSE) and S-100B were collected twice daily during five consecutive days. The initial (CTinit) and follow-up CT-scans (CT24h) were classified according to the Marshall, Rotterdam and Morris-Marshall classifications. Outcome was evaluated with extended Glasgow outcome scale (GOSE) at 3 months. There was a clear correlation of the maximal ICP (ICPmax) and minimal CPP (CPPmin) with the S-100B and NSE levels. A complex relation between biomarkers and the CT classifications were observed. Generally, the Marshall scores were correlated to the biomarker levels at 72 hrs and the Rotterdam scores correlated to the total (bulk) release. The Morris-Marshall scores correlated to all S-100B values, but not to any of the NSE values. A ROC curve analysis showed that the biomarkers had a moderate predictive value of mortality. S-100B bulk release and NSE at 72 hrs had the highest power in this prediction. A combination of the CT classification according to Morris-Marshall and the bulk release of S-100B further improved the prediction of clinical outcome.

National Category
Surgery
Research subject
Neurosurgery
Identifiers
URN: urn:nbn:se:umu:diva-85843OAI: oai:DiVA.org:umu-85843DiVA: diva2:695524
Available from: 2014-02-11 Created: 2014-02-11 Last updated: 2014-02-14Bibliographically approved
In thesis
1. Hormones, biomarkers, genetics and prognostication of patients suffering severe traumatic brain injury
Open this publication in new window or tab >>Hormones, biomarkers, genetics and prognostication of patients suffering severe traumatic brain injury
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Severe traumatic brain injury (sTBI) is a significant cause of mortality and mobidity worldwide. In Umeå University Hospital, at the department of Neurosurgery, patients with sTBI are treated by the Lund concept, which can be characterized as an intracranial pressure (ICP) targeted therapy.

In recent decades, there has been an increasing interest in trying to understand why some patients recover better and survive after sTBI, and why some do not. Also, improving the instruments of prognostication is becoming increasingly important both for relocating health resources and for the benefit of patients and relatives.

The main goal of the work described in this thesis was to explore factors influencing clinical outcome and improve the prognostication of outcome after sTBI. The ultimate goal is to improve the clinical outcome in patients suffering sTBI.

It has been proposed that the outcome after sTBI is influenced by genetic variability, including variability in apolipoprotein E (APOE). We therefore examined the relationship between the presence of APOE ε4 allele and the outcome. Except for 1 dichotomization of Glasgow outcome scale (GOS) at 3 months, the presence of the allele did not influence the outcome.

The biochemical markers of brain injury, S-100B and NSE, can be used to quantify the tissue lesion in sTBI. We investigated whether the levels of the biomarkers were associated with the APOE ε4 allele. Patients expressing the APOEε4 allele had significantly higher levels of S-100B than non-ε4 subjects. The temporal course of S-100B differed between the APOE groups. Similar, but not statistically significant results were observed for NSE. The results suggest that variations in genetics have to be considered when interpreting the biochemical markers.

We also found that serum levels of S-100B and NSE were correlated with ICPmax, CPPmin and radiological findings on brain CT quanttified by CT scoring systems and that S-100B and NSE (max and bulk release) may predict mortality.

The pituitary gland is vulnerable for traumatic events. This may be reflected in acute hormonal deviations, which can influence the clinical outcome. We found dynamic changes in hormone levels after sTBI. A large number of the patients had low cortisol levels, which were not however associated with an unfavourable outcome. We also found that a preserved capacity to a mutable hormonal response, i.e. fast and strong repression of the pituitary-gonadal axis and a capacity to re-establish activity in the pituitary-thyroid axis, was associated with less severe injury according to CT-findings and to a more favourable outcome after sTBI.

It is concluded that the presence of the APOEε4 allele did not indicate worse long-term outcome in our patient group. Patients expressing the APOEε4 allele, had significantly higher levels of S-100B than non-ε4 subjects, indicating that in some cases the genetics have to be considered when interpreting the biochemical markers. The biomarkers were also correlated to intracranial pressure and radiological findings, and may predict for mortality at 3 months. Profound hormonal changes in the acute phase occur. However, low levels of cortisol are not associated with a worse clinical outcome.

 

 

 

 

 

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2014. 60 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1624
National Category
Surgery
Research subject
Neurosurgery
Identifiers
urn:nbn:se:umu:diva-85845 (URN)978-91-7459-790-5 (ISBN)
Public defence
2014-03-07, sal E04, Norrlands universitetssjukhus, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2014-02-14 Created: 2014-02-11 Last updated: 2014-02-14Bibliographically approved

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