Risk for intracranial hemorrhage in individuals after mild traumatic brain injury who are taking serotonergic antidepressants

BackgroundSerotonergic antidepressants may predispose to bleeding, but little is known of the risk for traumatic intracranial bleeding. MethodsThis was a prospective case-control study of 218 patients with mild traumatic brain injuries (TBI) who were treated at a Finnish tertiary trauma hospital. Injury-related information and clinical findings were prospectively collected in the emergency department. Detailed pre-injury health history was collected from electronic medical records. Information on the use of serotonergic antidepressants was attained from the Finnish national prescription registry. All head CT scans were reviewed by a neuroradiologist based on the Common Data Elements. Cases were patients with traumatic intracranial hemorrhage on head CT. Controls were patients from the same cohort, but without traumatic intracranial lesions on CT. The proportion with traumatic intracranial bleeding for patients on serotonergic antidepressant medication was compared to the proportion for patients not on serotonergic medication. ResultsThe study cohort consisted of 24 cases with traumatic intracranial bleeding and 194 injured controls. The median age of the sample was 70 years (interquartile range = 50-83). One fifth (21.6%) of all the patients were taking a serotonergic antidepressant. Of the patients on an antidepressant, 10.6% (5/47) had an acute hemorrhagic lesion compared to 11.1% (19/171) of those who were not on an antidepressant (p = 0.927). In the regression analysis, traumatic intracranial hemorrhage was not associated with antidepressant use. ConclusionSerotonergic antidepressant use was not associated with an increased risk of traumatic intracranial hemorrhage after a mild TBI. The patients in this relatively small cohort were mostly middle-aged and older adults. These factors limit the generalizability of the results in younger patients with mild TBI.Peer reviewe

Examining four blood biomarkers for the detection of acute intracranial abnormalities following mild traumatic brain injury in older adults

Blood-based biomarkers have been increasingly studied for diagnostic and prognostic purposes in patients with mild traumatic brain injury (MTBI). Biomarker levels in blood have been shown to vary throughout age groups. Our aim was to study four blood biomarkers, glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament light (NF-L), and total tau (t-tau), in older adult patients with MTBI. The study sample was collected in the emergency department in Tampere University Hospital, Finland, between November 2015 and November 2016. All consecutive adult patients with head injury were eligible for inclusion. Serum samples were collected from the enrolled patients, which were frozen and later sent for biomarker analyses. Patients aged 60 years or older with MTBI, head computed tomography (CT) imaging, and available biomarker levels were eligible for this study. A total of 83 patients (mean age = 79.0, SD = 9.58, range = 60–100; 41.0% men) were included in the analysis. GFAP was the only biomarker to show statistically significant differentiation between patients with and without acute head CT abnormalities [U(83) = 280, p < 0.001, r = 0.44; area under the curve (AUC) = 0.79, 95% CI = 0.67–0.91]. The median UCH-L1 values were modestly greater in the abnormal head CT group vs. normal head CT group [U (83) = 492, p = 0.065, r = 0.20; AUC = 0.63, 95% CI = 0.49–0.77]. Older age was associated with biomarker levels in the normal head CT group, with the most prominent age associations being with NF-L (r = 0.56) and GFAP (r = 0.54). The results support the use of GFAP in detecting abnormal head CT findings in older adults with MTBIs. However, small sample sizes run the risk for producing non-replicable findings that may not generalize to the population and do not translate well to clinical use. Further studies should consider the potential effect of age on biomarker levels when establishing clinical cut-off values for detecting head CT abnormalities.publishedVersionPeer reviewe

Prospective Validation of the Scandinavian Guidelines for Initial Management of Minimal, Mild, and Moderate Head Injuries in Adults

The Scandinavian Guidelines for Initial Management of Minimal, Mild, and Moderate Head Injuries in Adults (Scandinavian guidelines) are the first to incorporate serum measurement of the S100 astroglial calcium-binding protein B (S100B) to emergency department (ED) triage of patients with head injury (HI). This prospective validation study was conducted in the ED of the Tampere University Hospital, Finland, between November 2015 and November 2016. All consecutive adult patients with HI presenting to the ED within 24 h from injury were eligible for inclusion. Venous blood for S100B sampling was drawn from all patients, and the result was available at the ED. Computed tomography (CT) scans of the head were performed according to the on-call physician's evaluation. Only the samples collected within 6 h after injury were used. A one-week follow-up was conducted to identify possible HI-related complications. A total of 295 patients (median age, 67.0 years, range, 18-100; women, 48.8%) were enrolled. Of those, 196 (66.4%) underwent scanning. Acute traumatic lesions were detected on 31 (15.8%) of the scans. Two of the CT-positive patients were scanned without a guidelines-based indication. These lesions did not require any specific treatment or repeated imaging. The guidelines-based sensitivity was 0.94 (95% confidence interval [CI], 0.77-0.99) and specificity 0.19 (95% CI, 0.13-0.26) for predicting traumatic intracranial CT abnormalities. The positive and negative predictive value for positive head CT was 0.18 (95% CI, 0.12-0.25) and 0.94 (95% CI, 0.78-0.99), respectively. In the mild-low risk group, no false negative S100B values were recorded. Thirteen patients (4.4%) were re-admitted to the ED, and two patients (0.7%) died one week after the primary HI. The deaths were unrelated to the injury. None of these adverse events were directly caused by a primarily undiagnosed intracranial injury. The Scandinavian guidelines incorporated with S100B are a valid means of screening clinically significant acute traumatic lesions after HI and have the potential to reduce unnecessary CT scanning

Comparing Glial Fibrillary Acidic Protein (GFAP) in Serum and Plasma Following Mild Traumatic Brain Injury in Older Adults

Objective:Identification and validation of blood-based biomarkers for the diagnosis and prognosis of mild traumatic brain injury (mTBI) is of critical importance. There have been calls for more research on mTBI in older adults. We compared blood-based protein marker glial fibrillary acidic protein (GFAP) concentrations in serum and in plasma within the same cohort of older adults and assessed their ability to discriminate between individuals based on intracranial abnormalities and functional outcome following mTBI. Methods:A sample of 121 older adults [>= 50 years old with head computed tomography (CT),n= 92] seeking medical care for a head injury [Glasgow Coma Scale scores of 14 (n= 6; 5.0%) or 15 (n= 115; 95.0%)] were enrolled from the emergency department (ED). The mean time between injury and blood sampling was 3.4 h (SD= 2.1; range = 0.5-11.7). Serum GFAP concentration was measured first using the Human Neurology 4-Plex Assay, while plasma GFAP concentration was later measured using the GFAP Discovery Kit, both on an HD-1 Single molecule array (Simoa) instrument. Glasgow Outcome Scale-Extended was assessed 1 week after injury. Results:Both serum and plasma GFAP levels were significantly higher in those with abnormal CT scans compared to those with normal head CT scans (plasma:U= 1,198,p< 0.001; serum:U= 1,253,p< 0.001). The ability to discriminate those with and without intracranial abnormalities was comparable between serum (AUC = 0.814) and plasma (AUC = 0.778). In the total sample, GFAP concentrations were considerably higher in plasma than in serum (Wilcoxon signed-rank testz= 0.42,p< 0.001,r= 0.42). Serum and plasma GFAP levels were highly correlated in the total sample and within all subgroups (Spearman'srhorange: 0.826-0.907). Both serum and plasma GFAP levels were significantly higher in those with poor compared to good functional outcome (serum:U= 1,625,p= 0.002; plasma:U= 1,539,p= 0.013). Neither plasma (AUC = 0.653) nor serum (AUC = 0.690) GFAP were adequate predictors of functional outcome 1 week after injury. Conclusions:Despite differences in concentration, serum and plasma GFAP levels were highly correlated and had similar discriminability between those with and without intracranial abnormalities on head CT following an mTBI. Neither serum nor plasma GFAP had adequate discriminability to identify patients who would have poor functional outcome