White Matter Abnormalities Associated With Prolonged Recovery in Adolescents Following Concussion

Abstract

Background: Concussion symptoms in adolescents typically resolve within 4 weeks. However, 20 – 30% of adolescents experience a prolonged recovery. Abnormalities in tracts implicated in visuospatial attention and emotional regulation (i.e., inferior longitudinal fasciculus, ILF; inferior fronto-occipital fasciculus, IFOF; uncinate fasciculus; UF) have been consistently reported in concussion; yet, to date, there are no objective markers of prolonged recovery in adolescents. Here, we evaluated the utility of diffusion MRI in outcome prediction. Forty-two adolescents (12.1 – 17.9 years; female: 44.0%) underwent a diffusion Magnetic Resonance Imaging (dMRI) protocol within the first 10 days of concussion. Based on days of injury until medical clearance, adolescents were then categorized into SHORT (<28 days; N = 21) or LONG (>28 days; N = 21) recovery time. Fractional anisotropy (FA) in the ILF, IFOF, UF, and/or concussion symptoms were used as predictors of recovery time (SHORT, LONG). Forty-two age- and sex-matched healthy controls served as reference. Higher FA in the ILF (left: adjusted odds ratio; AOR = 0.36, 95% CI = 0.15 – 0.91, P = 0.030; right: AOR = 0.28, 95% CI = 0.10 – 0.83, P = 0.021), IFOF (left: AOR = 0.21, 95% CI = 0.07 – 0.66, P = 0.008; right: AOR = 0.30, 95% CI = 0.11 – 0.83, P = 0.020), and UF (left: AOR = 0.26, 95% CI = 0.09 – 0.74, P = 0.011; right: AOR = 0.28, 95% CI = 0.10 – 0.73, P = 0.010) was associated with SHORT recovery. In additional analyses, while adolescents with SHORT recovery did not differ from HC, those with LONG recovery showed lower FA in the ILF and IFOF (P < 0.014). Notably, inclusion of dMRI findings increased the sensitivity and specificity (AUC = 0.93) of a prediction model including clinical variables only (AUC = 0.75). Our findings indicate that higher FA in long associative tracts (especially ILF) might inform a more objective and accurate prognosis for recovery time in adolescents following concussion.

Longitudinal white matter microstructural changes in pediatric mild traumatic brain injury: An A‐CAP study

“…This is indicative of more restricted water diffusion. Recent research similarly demonstrated higher FA in long association fibers in adolescents and young adults with short time to recovery and improved cognition following mTBI (Fakhran et al, 2014 ; Lima Santos et al, 2021 ; Mustafi et al, 2018 ). Higher FA is associated with greater resiliency during adolescence in typical development (Galinowski et al, 2015 ).…”

“…enhance clinical management in affected children with mTBI (Taylor et al, 2015). Inclusion of post-acute DTI metrics can increase the sensitivity and specificity of clinical prediction model for pediatric mTBI (Lima Santos et al, 2021) and FA values, specifically, were more predictive of recovery time than initial symptom burden in children and young adult (i.e., age 10-38 years) with mTBI in other studies (Fakhran et al, 2014). Previous findings also show that post-acute DTI is related to symptom burden in chronic periods after pediatric mTBI, but not differentially for children with mTBI as compared with mild OI (Ware et al, 2020).…”

“…However, no biomarker of prolonged recovery is currently available. Few studies have investigated the prognostic utility of DTI in pediatric mTBI and they have produced mixed results (Mayer et al, 2018 ) with associations between DTI metrics and symptom severity or duration found only in some of the studies (Lima Santos et al, 2021 ; Manning et al, 2017 ; Ware et al, 2020 ; Wilde et al, 2008 ). Because the neurophysiological effects of mTBI may persist after symptoms have resolved (Manning et al, 2017 ; Murdaugh et al, 2018 ) research addressing this knowledge gap is crucial for both understanding the neurobiology of mTBI and identifying objective neuroimaging biomarkers of prolonged recovery in affected children.…”

A window into eye movement dysfunction following mTBI: A scoping review of magnetic resonance imaging and eye tracking findings

“…Commonly found to show disruption in both mTBI (Jia et al., 2021 ; Lima Santos et al., 2021 ) and subconcussive impacts (Bahrami et al., 2016 ) due to its lengthy course from anterior/posterior, residing along a sagittal plane (Zhao et al., 2017 )…”

“…Numerous groups have correlated UF integrity to behavioral outcomes (C. P. Johnson et al., 2011 ), eye movement deficits (Maruta et al., 2010 ; Taghdiri et al., 2018 ), and mTBI diagnosis (Lima Santos et al., 2021 ; Murdaugh et al., 2018 ; Seo et al., 2012 )…”