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Fatigue may be among the most profound and debilitating consequences of pediatric traumatic brain injury (TBI); however, neurostructural risk factors associated with post-injury fatigue remain elusive. This prospective study aimed to evaluate the independent value of susceptibility-weighted imaging (SWI) biomarkers, over-and-above known risk factors, to predict fatigue symptom severity in children with TBI. Forty-two children were examined with structural magnetic resonance imaging (sMRI), including a SWI sequence, within eight weeks post-injury. The PedsQL Multi-Dimensional Fatigue Scale (MFS) was administered 24 months post-injury. Compared with population expectations, the TBI group displayed significantly higher levels of general fatigue (Cohen d = 0.44), cognitive fatigue (Cohen d = 0.59), sleep/rest fatigue (Cohen d = 0.37), and total fatigue (Cohen d = 0.63). In multi-variate models adjusted for TBI severity, child demographic factors, and depression, we found that subacute volume of SWI lesions was independently associated with all fatigue symptom domains. The magnitude of the brain-behavior relationship varied by fatigue symptom domain, such that the strongest relationships were observed for the cognitive fatigue and total fatigue symptom scales. Overall, we found that total subacute volume of SWI lesions explained up to 24% additional variance in multi-dimensional fatigue, over-and-above known risk factors. The subacute SWI has potential to improve prediction of post-injury fatigue in children with TBI. Our preliminary findings suggest that volume of SWI lesions may represent a novel, independent biomarker of post-injury fatigue, which could help to identify high-risk children who are likely to benefit from targeted psychoeducation and/or preventive strategies to minimize risk of long-term post-injury fatigue. [ABSTRACT FROM AUTHOR]

Although childhood traumatic brain injury (TBI) has been linked to heightened risk of impaired social skills and behavior, current evidence is weakened by small studies of variable methodological quality. To address these weaknesses, this international multi-cohort study involved synthesis of data from two large observational cohort studies of complicated mild-severe child TBI in Australia and North America. Both studies adopted a unified approach to data collection and coding procedures, providing the opportunity to merge datasets from multiple, well-characterized cohorts for which gold standard measures of social outcomes were collected during the chronic recovery phase. The study involved 218 children, including 33 children with severe TBI, 83 children with complicated mild-moderate TBI, 59 children with orthopedic injury, and 43 age- and sex-matched typically developing control children. All injured children were recruited from academic children's hospitals and underwent direct cognitive assessments including measures of theory of mind (ToM) at least 1-year post- injury. Parents rated their child's social adjustment using standardized measures of social skills, communication and behavior. Results showed a brain-injury specific effect on ToM abilities, such that children with both complicated mild to moderate and severe TBI displayed significantly poorer ToM than children without TBI. In mediator models, poorer ToM predicted poorer parent-rated self-direction and social skills, as well as more frequent behavioral symptoms. The ToM mediated the effect of severe TBI on parent ratings of communication and social skills, as well as on overall behavior symptoms. The findings suggest that deficits in ToM are evident across the spectrum of TBI severity and represent one mechanism linking severe child TBI to long-term social adjustment difficulties. The findings underscore the value of large-scale data harmonization projects to increase the quality of evidence regarding the outcomes of TBI. Clinical and scientific implications are discussed. [ABSTRACT FROM AUTHOR]