Preliminary Evaluation of the Scandinavian Guidelines for Initial Management of Minimal, Mild, and Moderate Head Injuries with Glial Fibrillary Acidic Protein.

Glial fibrillary acidic protein (GFAP) has become the most promising biomarker for detecting traumatic abnormalities on head computed tomography (CT) in patients with traumatic brain injury (TBI), but most studies have not addressed the potential added value of combining the biomarker with clinical variables that confer risk for intracranial injuries. The Scandinavian Guidelines for Initial Management of Minimal, Mild, and Moderate Head Injuries in Adults were the first clinical decision rules in the field with an incorporated biomarker, the S100 astroglial calcium-binding protein B (S100B), which is used in the Mild (Low Risk) group defined by the guidelines. Our aim was to evaluate the performance of the guidelines when S100B was substituted with GFAP. The sample (N = 296) was recruited from the Tampere University Hospital's emergency department between November 2015 and November 2016, and there were 49 patients with available GFAP results who were stratified in the Mild (Low Risk) group (thus patients undergoing biomarker triaging). A previously reported cutoff of plasma GFAP ≥140 pg/mL was used. Within the Mild (Low Risk) group (n = 49), GFAP sensitivity (with 95% confidence intervals in parentheses) for detecting traumatic CT abnormalities was 1.0 (0.40-1.00), specificity 0.34 (0.19-0.53), the negative predictive value (NPV) 1.0 (0.68-1.00), and the positive predictive value (PPV) 0.16 (0.05-0.37). The sensitivity and specificity of the modified guidelines with GFAP, when applied to all imaged patients (n = 197) in the whole sample, were 0.94 (0.77-0.99) and 0.20 (0.15-0.28), respectively. NPV was 0.94 (0.80-0.99) and PPV 0.18 (0.13-0.25). In the Mild (Low Risk) group, none of the patients with GFAP results below 140 pg/mL had traumatic abnormalities on their head CT. These findings were derived from a small patient subgroup. Future researchers should replicate these findings in larger samples and assess whether GFAP has added or comparable value to S100B in acute TBI management.

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.

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

Background: Serotonergic antidepressants may predispose to bleeding, but little is known of the risk for traumatic intracranial bleeding. Methods: This 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. Results: The 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. Conclusion: Serotonergic 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.

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 test z = 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's rho range: 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.

Complicated mild traumatic brain injury in older adults: Post-concussion symptoms and functional outcome at one week post injury.

Primary Objective: Mild Traumatic Brain Injury (MTBI) is commonly categorized as complicated when injury severity criteria are mild, but an intracranial abnormality is present on acute neuroimaging. The current study examined whether functional outcomes differed at one week post injury among older adult patients based on injury severity and acute computed tomography (CT) findings.Research Design: Participants (≥55 years-old; n = 173) presenting sequentially to the emergency department with a head injury were divided into three groups: complicated MTBI (positive CT; n = 22), uncomplicated MTBI (negative CT; n = 68), and mild head injury (unperformed CT, no documented loss of consciousness or post-traumatic amnesia; n = 83).Methods and Procedures: At one week post injury, the Modified Rankin Scale (i.e., difference score between pre/post-injury ratings; ∆MRS), Glasgow Outcome Scale-Extended (GOS-E), and Rivermead Post-Concussion Symptoms Questionnaire (RPQ) were administered.Main Outcomes and Results: Participants differed on the ∆MRS and GOS-E, but not the RPQ. The complicated MTBI group had worse GOS-E ratings than the uncomplicated MTBI and mild head injury groups and worse ∆MRS than the mild head injury group, but the uncomplicated MTBI and mild head injury groups did not differ on either outcome.Conclusions: Macrostructural abnormality on CT was associated with worse functional outcome at one week post MTBI.

Age, symptoms, and functional outcome after mild traumatic brain injury.

OBJECTIVES: Previous older adult studies have examined outcome from moderate-to-severe traumatic brain injury (TBI), but fewer have focused on the effects of milder brain injuries. This study examined age-related differences in symptom reporting and whether symptoms are differentially related to functional outcome based on age. MATERIALS & METHODS: Patients presenting with a head injury at the Tampere University Hospital emergency department (N = 325, aged 18-100) were evaluated at 1 week post injury on the Modified Rankin Scale and Rivermead Post Concussion Symptoms Questionnaire (RPQ). RESULTS: A quarter of participants had missing RPQ data, with missingness associated with greater age and strongly associated with pre-existing functional impairment, dementia, and/or neurological conditions. Among participants with complete data, participants <65 years old endorsed headaches, noise/light sensitivity, irritability, and frustration/impatience at a greater frequency than participants ≥65 years old. However, no differences were found in the number of symptoms endorsed or the total symptom severity score. The correlations between the severity of symptoms and change in function were similar between the two age groups. CONCLUSIONS: Older adults tended to report fewer symptoms, but symptoms had a roughly equivalent relationship with declines in functioning across age groups. A large percentage of older adults in this study had pre-injury dementia or neurological disease that contributed to missing data on the 1-week outcome measures. The results provide insight into the impact of mild spectrum TBI on older adults compared to younger patients.

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.