Orthopedic Injured versus Uninjured Comparison Groups for Neuroimaging Research in Mild Traumatic Brain Injury

Abstract

To address controversy surrounding the most appropriate comparison group for mild traumatic brain injury (mTBI) research, mTBI patients 12-30 years of age were compared with an extracranial orthopedic injury (OI) patient group and an uninjured, typically developing (TD) participant group with comparable demographic backgrounds. Injured participants underwent subacute (within 96 h) and late (3 months) diffusion tensor imaging (DTI); TD controls underwent DTI once. Group differences in fractional anisotropy (FA) and mean diffusivity (MD) of commonly studied white matter tracts were assessed. For FA, subacute group differences occurred in the bilateral inferior frontal occipital fasciculus (IFOF) and right inferior longitudinal fasciculus (ILF), and for MD, differences were found in the total corpus callosum, right uncinate fasciculus, IFOF, ILF, and bilateral cingulum bundle (CB). In these analyses, differences (lower FA and higher MD) were generally observed between the mTBI and TD groups but not between the mTBI and OI groups. After a 3 month interval, groups significantly differed in left IFOF FA and in right IFOF and CB MD; the TD group had significantly higher FA and lower MD than both injury groups, which did not differ. There was one exception to this pattern, in which the OI group demonstrated significantly lower FA in the left ILF than the TD group, although neither group differed from the mTBI group. The mTBI and OI groups had generally similar longitudinal results. Findings suggest that different conclusions about group-level DTI analyses could be drawn, depending on the selected comparison group, highlighting the need for additional research in this area. Where possible, mTBI studies may benefit from the inclusion of both OI and TD controls.

Post-acute white matter microstructure predicts post-acute and chronic post-concussive symptom severity following mild traumatic brain injury in children

“…DTI was used to measure early post-acute (i.e., within 2-weeks post-injury) white matter microstructure. Few group differences (mild TBI vs. OI) in early post-acute DTI metrics (i.e., FA and MD) were expected given recent findings from a larger sample of adolescents and young adults (Wilde et al., 2018b). We also examined relations between post-acute DTI metrics and PCS ratings at approximately 2 weeks, 3 months, and 6 months post-injury.…”

“…DTI studies of pediatric mild TBI have generally relied on small sample sizes that have been highly heterogeneous with regards to participant and injury characteristics (Dodd et al., 2014). Age ranges of participants have varied widely between studies (Babcock et al., 2015; Chu et al., 2010; Ewing-Cobbs et al., 2019; Mayer et al., 2010; Mustafi et al., 2018; Wilde et al., 2018b, 2008; Wozniak et al., 2007). Given that childhood is a period of dynamic maturation, further investigation of a broad age range in a single, larger sample is warranted to help determine whether mild TBI affects expected age-related trajectories of white matter development.…”

“…It also does not control for post-injury factors such as psychological stress in response to trauma, pain, or effects related to medical treatment. A recent DTI study found that white matter microstructure characteristics of adolescents and young adults with mild TBI or OI were generally similar, but differed from a third group of healthy controls (Wilde et al., 2018b). Finally, practical reasons exist for including an extracranial or OI group; namely, they are more clinically relevant, given that health care providers must determine whether children with traumatic injuries sustained a mild TBI and are at risk for further complications.…”

Longitudinal Neuroimaging in Pediatric Traumatic Brain Injury: Current State and Consideration of Factors That Influence Recovery

“…While acknowledging the strengths and limitations of each group, the authors conclude that the selection of a single comparison group may contribute to the inconsistency in dMRI findings reported in the literature. Wilde et al (177) suggest that conclusions drawn from studies utilizing a typicallydeveloping comparison group may be different if the studies had instead included an orthopedically-injured comparison group and therefore recommend the use of both comparison groups, if possible; however, further investigation of this issue is clearly warranted.…”

Kids’ Outcomes And Long-term Abilities (KOALA): protocol for a prospective, longitudinal cohort study of mild traumatic brain injury in children 6 months to 6 years of age

“… 49 50 Both OI and CC groups will be be included here to ensure the findings in the mTBI group are brain injury-specific, given that previous work in this age group has not verified the comparability of OI and CC groups on all of the study variables of interest. 51 …”