Objective:To determine if neurofilament light (NfL), glial fibrillary acidic protein (GFAp), tau, and ubiquitin C-terminal hydrolase-L1 (UCH-L1) measured in serum relate to traumatic brain injury (TBI) diagnosis, injury severity, brain volume, and diffusion tensor imaging (DTI) measures of traumatic axonal injury (TAI) in patients with TBI.Methods:Patients with TBI (n=162) and controls (n=68) were prospectively enrolled between 2009–2018. Of the 162 patients, 102 underwent repeated serum, functional outcome, brain MRI volumetry, and DTI assessments at 30, 90, and 180 days, and 1, 2, 3, 4, and 5 years after TBI.Results:At enrolment, patients with TBI had increased serum NfL compared to controls (p<0.0001). Serum NfL decreased over the course of five years, but remained significantly elevated compared to controls. Serum NfL at 30 days distinguished patients with mild, moderate, and severe TBI from controls with Area Under the Receiver-Operating Characteristic Curve (AUROC) of 0.84, 0.92, and 0.92, respectively. At enrolment, serum GFAp was elevated in TBI patients compared to controls (p<0.001). GFAp showed a biphasic release in serum, with levels decreasing during the first six months of injury, whereafter increased over the subsequent study visits. The highest AUROC for GFAp was measured at 30 days distinguishing moderate and severe TBI patients from controls (both 0.89). Serum tau and UCH-L1 showed weak associations to TBI severity and neuroimaging measures. Longitudinally, serum NfL was the only biomarker that was associated with the likely rate of MRI brain atrophy and DTI measures of progression of TAI.Conclusions:Serum NfL shows greater diagnostic and prognostic utility than GFAp, tau, and UCH-L1 for subacute and chronic TBI.Classification of Evidence:This study provides Class III evidence that serum NfL distinguishes patients with mild TBI from healthy controls.

Objective:To determine if serum neurofilament light (NfL) correlates with cerebrospinal fluid (CSF) NfL, TBI diagnosis, injury severity, brain volume, and diffusion tensor imaging (DTI) estimates of traumatic axonal injury (TAI).Methods:Participants were prospectively enrolled in Sweden and the United States between 2011-2019. The Swedish cohort included 45 hockey players with acute concussion (AC) sampled at six days, 31 repetitive concussion (RC) with persistent post-concussive symptoms (PCS) assessed with paired CSF and serum (median, 1.3 years after concussion), 28 preseason controls, and 14 non-athletic controls. Our second cohort included 230 clinic-based participants (162 with TBI and 68 controls. Patients with TBI also underwent serum, functional outcome, and imaging assessments at 30 (n=30), 90 (n=48), and 180 (n=59) days, and 1 (n=84), 2 (n=57), 3 (n=46), 4 (n=38), and 5 (n=29) years after injury.Results:In athletes with paired specimens, CSF and serum NfL were correlated (r=0.71, p<0.0001). CSF and serum NfL distinguished players with PCS >1-year from PCS ≤1-year (Area Under the Receiver-Operating Characteristic Curve [AUROC], 0.81 and 0.80). The AUROC for PCS >1-year vs preseason controls were 0.97. In the clinic-based cohort, NfL at enrolment distinguished patients with mild vs moderate vs severe TBI (p<0.001 and p=0.048). Serum NfL decreased over the course of five years (ß=–0.09 log pg/mL, p<0.0001), but remained significantly elevated compared to controls. Serum NfL correlated with measures of functional outcome, MRI brain atrophy, and DTI estimates of TAI.Conclusions:Serum NfL shows promise as a biomarker for acute and repetitive sports-related concussion and patients with subacute and chronic TBI.Classification of Evidence:This study provides Class III evidence that increased concentrations of NfL distinguish TBI from controls.

The Kv1.1 null mouse is a potential model for SUDEP in patients who experience ictal and postictal bradycardia. It offers the opportunity for evaluation of the combination of factors, in addition to vagal activation, necessary to produce a terminal asystole following seizure. It is notable that long-term studies that evaluate electroencephalography (EEG) and cardiorespiratory events surrounding nonfatal seizures may provide indices predictive of terminal seizure.

Resilience is associated with bouncing back from adversity, and the term currently enjoys significant popular appeal. However, understanding of resilience is often superficial. The current paper examined 105 primary and high school students' experiences of resilience and bullying, and considered resilience as a hierarchical factorial model. The study found that higher levels of resilience subfactors were a protective factor regarding depression and anxiety; that individuals with poorer resilience were more likely to engage in bullying behaviors; that individuals with poorer levels of resilience were more likely to be victims of bullying; and, that gender did not appear to be a major variable regarding resilience and bullying. These findings suggest that resilience interventions that focus on improving specific resilience elements including optimism, trust, tolerance, sensitivity, and impairment may be more efficacious than interventions focused on other resilience elements.

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Anti-bullying policies and interventions are the main approach addressing bullying behaviours in Australian schools. However, the evidence supporting these approaches is inconsistent and its theoretical underpinning may be problematic. The current study examined the effects of a martial arts based psycho-social intervention on participants’ ratings of resilience and self-efficacy, delivered as a randomised controlled trial to 283 secondary school students. Results found a consistent pattern for strengths-based wellbeing outcomes. All measures relating to resilience and self-efficacy improved for the intervention group, whereas results declined for the control group. These findings suggest that a martial arts based psycho-social intervention may be an efficacious method of improving wellbeing outcomes including resilience and self-efficacy. The study proposes utilising alternatives to the anti-bullying approach and that interventions should be aimed towards helping individuals develop strengths and cope more effectively, which has specific relevance to bullying and more generalised importance to positive mental health.

Traumatic brain injury (TBI) is linked to long-term symptoms in a sub-set of patients who sustain an injury, but this risk is not universal, leading us and others to question the nature of individual variability in recovery trajectories. Extracellular vesicles (EVs) are a promising, novel avenue to identify blood-based biomarkers for TBI. Here, our aim was to determine if glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) measured 1-year postinjury in EVs could distinguish patients from controls, and whether these biomarkers relate to TBI severity or recovery outcomes. EV GFAP and EV NfL were measured using an ultrasensitive assay in 72 TBI patients and 20 controls. EV GFAP concentrations were elevated in moderate and severe TBI compared to controls (p’s < 0.001) and could distinguish controls from moderate (AUC = 0.86) or severe TBI (AUC = 0.88). Increased EV GFAP and EV NfL levels were associated with lower 1-year Glasgow Outcome Scale–Extended (GOS-E) score (p’s < 0.05). These findings suggest that blood-derived EV concentrations of GFAP and NfL drawn even 1 year after injury are higher in TBI patients compared to controls, and are related to injury severity and poor recovery outcomes, suggesting that TBIs alter the activity of these biomarkers, likely contributing to individual variability in recovery.

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