Neurofilament light as a biomarker in traumatic brain injury.

OBJECTIVE: To determine whether serum neurofilament light (NfL) correlates with CSF NfL, traumatic brain injury (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 and 2019. The Swedish cohort included 45 hockey players with acute concussion sampled at 6 days, 31 with repetitive concussion with persistent postconcussive symptoms (PCS) assessed with paired CSF and serum (median 1.3 years after concussion), 28 preseason controls, and 14 nonathletic 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 NfL 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 was 0.97. In the clinic-based cohort, NfL at enrollment distinguished patients with mild from those with moderate and severe TBI (p < 0.001 and p = 0.048). Serum NfL decreased over the course of 5 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 patients with TBI from controls.

Time course and diagnostic utility of NfL, tau, GFAP, and UCH-L1 in subacute and chronic TBI.

OBJECTIVE: To determine whether 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 2011 and 2019. 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: At enrollment, patients with TBI had increased serum NfL compared to controls (p < 0.0001). Serum NfL decreased over the course of 5 years but remained significantly elevated compared to controls. Serum NfL at 30 days distinguished patients with mild, moderate, and severe TBI from controls with an area under the receiver-operating characteristic curve (AUROC) of 0.84, 0.92, and 0.92, respectively. At enrollment, serum GFAP was elevated in patients with TBI compared to controls (p < 0.001). GFAP showed a biphasic release in serum, with levels decreasing during the first 6 months of injury but increasing over the subsequent study visits. The highest AUROC for GFAP was measured at 30 days, distinguishing patients with moderate and severe TBI from controls (both 0.89). Serum tau and UCH-L1 showed weak associations with 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.

Evidence-based systematic review of cognitive rehabilitation, emotional, and family treatment studies for children with acquired brain injury literature: From 2006 to 2017.

This paper updates guidelines for effective treatments of children with specific types of acquired brain injury (ABI) published in 2007 with more recent evidence. A systematic search was conducted for articles published from 2006 to 2017. Full manuscripts describing treatments of children (post-birth to 18) with acquired brain injury were included if study was published in peer-reviewed journals and written in English. Two independent reviewers and a third, if conflicts existed, evaluated the methodological quality of studies with an Individual Study Review Form and a Joanna Briggs Institute (JBI) Critical Appraisal Checklist. Strength of study characteristics was used in development of practice guidelines. Fifty-six peer-reviewed articles, including 27 Class I studies, were included in the final analysis. Established guidelines for writing practice recommendations were used and 22 practice recommendations were written with details of potential treatment limitations. There was strong evidence for family/caregiver-focused interventions, as well as direct interventions to improve attention, memory, executive functioning, and emotional/behavioural functioning. A majority of the practice standards and guidelines provided evidence for the use of technology in delivery of interventions, representing an important trend in the field.

Detection of text-based social cues in adults with traumatic brain injury.

OBJECTIVES: Written text contains verbal immediacy cues-word form or grammatical cues that indicate positive attitude or liking towards an object, action, or person. We asked if adults with moderate-severe traumatic brain injury (TBI) would respond to these cues, given evidence of TBI-related social communication impairments. METHODS: Sixty-nine adults with TBI and 74 healthy comparison (HC) peers read pairs of sentences containing different types of immediacy cues (e.g., speaker A said "these Canadians" vs. B said "those Canadians.") and identified which speaker (A or B) had a more positive attitude towards the underlined entity (Task 1); and pairs of sentences comprised of a context sentence (e.g., Fred is asked, "Did you visit Joan and Sue?") and a statement sentence (Fred says, "I visited Sue and Joan.") and were asked to indicate how much Fred liked or disliked the underlined words (Task 2). RESULTS: HC group scores were significantly higher on Task 1, indicating more sensitivity to cues. On Task 2, TBI and HC group ratings differed across cue types and immediacy types, and the TBI group appeared to have less sensitivity to these cues. CONCLUSIONS: Findings suggest that TBI-related impairments may reduce sensitivity to subtle social cues in text.

Cognitive-communication disorders in children with traumatic brain injury.

Children with moderate to severe traumatic brain injury (TBI) are at risk of developing cognitive-communication disorders that have devastating effects on their school life, family life, and social life. These problems can be difficult for families to describe and may be overlooked by community-based providers who are unfamiliar with TBI sequelae. To support the identification and management of cognitive-communication disorders, we review the common signs and symptoms of these disorders in children with TBI and discuss principles of assessment and intervention.