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The apolipoprotein E epsilon4 allele and outcome in severe traumatic brain injury treated by an intracranial pressure-targeted therapy
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
2010 (English)In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 112, no 5, 1113-1119 p.Article in journal (Refereed) Published
Abstract [en]

The presence of epsilon4 is not associated with long-term clinical outcome in patients with severe TBI treated with an ICP targeted therapy, based on the Lund concept.

Place, publisher, year, edition, pages
2010. Vol. 112, no 5, 1113-1119 p.
Keyword [en]
apolipoprotein E; ε4 allele; severe traumatic brain injury; outcome; prediction
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:umu:diva-42318DOI: 10.3171/2009.8.JNS09636PubMedID: 19747047OAI: oai:DiVA.org:umu-42318DiVA: diva2:409106
Available from: 2011-04-07 Created: 2011-04-07 Last updated: 2017-12-11Bibliographically 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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