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Object: In this paper we tested the hypothesis if patients with severe traumatic brain injury and presence of the apolipoprotein E (APOE) epsilon 4 allele are more prone to undergo the surgical procedure decompressive hemicraniectomy (DC) in order to bring the intracranial pressure (ICP) under control. Methods: In this prospective consecutive study patients with sTBI were enrolled (n = 48). Inclusion criteria were arrival to our level one trauma university hospital within 24 h after trauma, patient age between 15 and 70 years, Glasgow Coma Scale (GCS) score <= 8 at the time of intubation and sedation, an initial cerebral perfusion pressure >10 mm Hg. Venous blood was sampled for APOE genotype determination. Clinical outcome at 6 months after injury was assessed with the Extended Glasgow Outcome Scale (GOSE). All surgical procedures needed for each patient were registered. Results: Patients with the APOE epsilon 4 allele were significantly overrepresented in the DC group. In the APOE epsilon 4 + DC group, ICPmax and ICPmean mean during the first 36 h were significantly higher and GOSE was significantly worse at 6 months. Conclusion: Our data suggest that patients with the APOE epsilon 4 allele are predisposed for the need of DC more often than patients without the APOE epsilon 4 allele. Thus, it seems to be of importance to consider the APOE genotype in patients suffering severe traumatic brain injury in order to forecast the need for a more exquisite intensive care. (C) 2017 Published by Elsevier Ltd.

Gait disturbances and falls are common in patients with chronic subdural hematoma (cSDH). Postural stability is mainly visually assessed and has not been described using an objective and quantitative measurement tool. The objective of this prospective study was to evaluate postural stability in cSDH patients by measuring trunk sway during stance and gait compared to healthy elderly (HE). It was also to evaluate the relationships among postural stability and age, hematoma size, brain midline shift and hematoma location. Using a gyroscopic method, trunk sway was measured in 22 cSDH patients preoperatively, 5 postoperatively and 58 HE during seven standing and walking tasks. Trunk sway amplitude and velocity in the anterior-posterior and medial-lateral directions were assessed. Postural stability was reduced in the cSDH group compared to HE for all standing tasks. During gait, the sway angle was increased while velocity was decreased in the cSDH group. Only 18 % of the patients could perform all tasks without losing their balance. Postoperatively, postural stability was normalized in the medial-lateral direction during standing. There were no correlations among age, hematoma size, brain midline shift or location of the hematoma and trunk sway. The majority of cSDH patients had reduced postural stability that was partly reversed soon after surgery. It was not correlated to hematoma characteristics, indicating that an increased risk to fall is present regardless of hematoma size and midline shift. This must be accounted for when handling these patients and measures taken to prevent further fall accidents during hospital stays.

Objective: The association was studied of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) on S-100B and neuron-specific enolase (NSE) in severe traumatic brain injury (sTBI). The relationship was explored between biomarkers, ICP, CPP, CT-scan classifications and the clinical outcome.

Materials and methods: Data were collected prospectively and consecutively in 48 patients with Glasgow Coma Scale score ≤ 8, age 15–70 years. NSE and S-100B were analysed during 5 consecutive days. The initial and follow-up CT-scans were classified according to the Marshall, Rotterdam and Morris-Marshall classifications. Outcome was evaluated with extended Glasgow outcome scale at 3 months.

Results: Maximal ICP and minimal CPP correlated with S-100B and NSE levels. Complex relations between biomarkers and CT classifications were observed. S-100B bulk release (AUC = 0.8333, p = 0.0009), and NSE at 72 hours (AUC = 0.8476, p = 0.0045) had the highest prediction power of mortality. Combining Morris-Marshall score and S-100B bulk release improved the prediction of clinical outcome (AUC = 0.8929, p = 0.0008).

Conclusion: Biomarker levels are associated with ICP and CPP and reflect different aspects of brain injury as evaluated by CT-scan. The biomarkers might predict mortality. There are several pitfalls influencing the interpretation of biomarker data in respect to ICP, CPP, CT-findings and clinical outcome.

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 ICP_max, CPP_min 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.

Object: The aim of the study was to evaluate the early changes in pituitary hormone levels after severe traumatic brain injury (sTBI) and compare hormone levels to basic neuro-intensive care data, a systematic scoring of the CT-findings and to evaluate whether hormone changes are related to outcome.

Methods: Prospective study, including consecutive patients, 15-70 years, with sTBI, Glasgow Coma Scale (GCS) score <= 8, initial cerebral perfusion pressure > 10 mm Hg, and arrival to our level one trauma university hospital within 24 hours after head trauma (n = 48). Serum samples were collected in the morning (08-10 am) day 1 and day 4 after sTBI for analysis of cortisol, growth hormone (GH), prolactin, insulin-like growth factor 1 (IGF-1), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), follicular stimulating hormone (FSH), luteinizing hormone (LH), testosterone and sex hormone-binding globulin (SHBG) (men). Serum for cortisol and GH was also obtained in the evening (17-19 pm) at day 1 and day 4. The first CT of the brain was classified according to Marshall. Independent staff evaluated outcome at 3 months using GOS-E.

Results: Profound changes were found for most pituitary-dependent hormones in the acute phase after sTBI, i.e. low levels of thyroid hormones, strong suppression of the pituitary-gonadal axis and increased levels of prolactin. The main findings of this study were: 1) A large proportion (54% day 1 and 70% day 4) of the patients showed morning s-cortisol levels below the proposed cut-off levels for critical illness related corticosteroid insufficiency (CIRCI), i.e. < 276 nmol/L (= 10 ug/dL), 2) Low s-cortisol was not associated with higher mortality or worse outcome at 3 months, 3) There was a significant association between early (day 1) and strong suppression of the pituitary-gonadal axis and improved survival and favorable functional outcome 3 months after sTBI, 4) Significantly lower levels of fT3 and TSH at day 4 in patients with a poor outcome at 3 months. 5) A higher Marshall CT score was associated with higher day 1 LH/FSH-and lower day 4 TSH levels 6) In general no significant correlation between GCS, ICP or CPP and hormone levels were detected. Only ICPmax and LH day 1 in men was significantly correlated.

Conclusion: Profound dynamic changes in hormone levels are found in the acute phase of sTBI. This is consistent with previous findings in different groups of critically ill patients, most of which are likely to be attributed to physiological adaptation to acute illness. Low cortisol levels were a common finding, and not associated with unfavorable outcome. A retained ability to a dynamic hormonal response, i.e. fast and strong suppression of the pituitary-gonadal axis (day 1) and ability to restore activity in the pituitary-thyroid axis (day 4) was associated with less severe injury according to CT-findings and favorable outcome.

Based on the Corticosteroid Randomisation after Significant Head Injury (CRASH) trial database, a prognosis calculator has been developed for the prediction of outcome in an individual patient with a head injury. In 47 patients with severe traumatic brain injury (sTBI) prospectively treated using an intracranial pressure (ICP) targeted therapy, the individual prognosis for mortality at 14 days and unfavourable outcome at 6 months was calculated and compared with the actual outcome. An overestimation of the risk of mortality and unfavourable outcome was found. The mean risk for mortality and unfavourable outcome were estimated to be 44.6 +/- 32.5% (95% confidence interval [CI], 35.1-54.2%) and 69.3 +/- 23.7% (95% CI, 62.3-76.2%). The actual outcome was 4.3% and 42.6% respectively. The absolute risk reduction (ARR) for mortality was 33.1% and for unfavourable outcome 29.8%. A logistic fit for outcome at 6 months shows a statistically significant difference (p < 0.01). A receiver operating characteristic (ROC) curve analysis shows an area under the curve (AUC) of 0.691. The CRASH prognosis calculator overestimates the risk of mortality and unfavourable outcome in patients with sTBI treated with an ICP-targeted therapy based on the Lund concept. We do not advocate the use of the calculator for treatment decisions in individual patients. We further conclude that patients with blunt sTBI admitted within 8 hours of trauma should be treated regardless of their clinical status as long as the initial cerebral perfusion pressure is > 10 mmHg.

In this article we tested the hypothesis that the level of two biochemical markers of brain injury may be associated with the apolipoprotein E (APOE) epsilon 4 allele. In this prospective consecutive study patients with sTBI were included (n = 48). Inclusion criteria were Glasgow Coma Scale (GCS) score a parts per thousand currency signaEuro parts per thousand 8 at the time of intubation and sedation, patient age between 15 and 70 years, an initial cerebral perfusion pressure > 10 mmHg, and arrival to our level-one trauma university hospital within 24 h after trauma. Blood samples for neuron-specific enolase (NSE) and S-100B were collected as soon as possibly after arrival, and then twice daily (12-h intervals) for 5 consecutive days. Venous blood was used for APOE genotype determination. Clinical outcome at 3 months after injury was assessed with the Extended Glasgow Outcome Scale (GOSE). Significantly higher levels of the maximal S-100B (S-100B(max)) and area under the curve (S-100B(AUC)) were found in subjects with the APOE epsilon 4 allele compared to those with non-epsilon 4. A similar tendency was observed for NSEmax and NSEAUC, though not statistically significant. Our data indicate that there might be a gene-induced susceptibility to severe traumatic brain injury and that patients with the APOE epsilon 4 allele may be more predisposed to brain cellular damage measured as S-100B and NSE. Thus, it seems to be of importance to consider the APOE genotype in interpreting the levels of the biomarkers.

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.

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 (CT_init) and follow-up CT-scans (CT_24h) 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 (ICP_max) and minimal CPP (CPP_min) 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.