White matter fiber morphology in persisting postconcussive symptoms and posttraumatic headache after pediatric
Feiven Fan1,2, Richard Beare1,3,4, Sila Genc4,5
11Murdoch Children's Research Institute, Parkville.
Insights
This study found no differences in white matter microstructure between children with persistent postconcussive symptoms (PCS) and recovered children 2 weeks after concussion. These findings suggest that fiber-specific imaging may not be a reliable biomarker for PCS in pediatric concussion patients.
Area of Science:
- Neuroimaging
- Pediatric Neurology
- Traumatic Brain Injury
Background:
- Posttraumatic headache (PTH) is a common persistent symptom after pediatric concussion.
- Objective biomarkers for risk stratification and early intervention in pediatric concussion are lacking.
- Fixel-based analysis (FBA) of diffusion-weighted imaging (DWI) offers improved sensitivity for detecting white matter changes compared to traditional methods.
Purpose of the Study:
- To investigate whole-brain and tract-based white matter morphology differences in children with postconcussive symptoms (PCS) and PTH.
- To assess fiber density (FD) and fiber bundle cross-section (FC) area at 2 weeks post-concussion using FBA.
- To determine if FBA can identify biomarkers for persistent symptoms after pediatric concussion.
Main Methods:
- Prospective longitudinal study of children (5-18 years) with concussion.
- Diffusion-weighted MRI acquired at 2 weeks post-injury.
- Whole-brain FBA (connectivity-based fixel enhancement) and tract-based Bayesian analysis performed.
Main Results:
- No significant differences in fiber-specific white matter microstructure (FD, FC, FDC) were found between recovered and symptomatic children, or between PTH and non-PTH groups.
- Tract-based analysis revealed no effect of PTH or recovery status on white matter fiber density.
- Results remained non-significant after adjusting for age and sex and applying family-wise error rate correction.
Conclusions:
- Fiber-specific white matter microstructure does not differ between children with and without persistent PCS 2 weeks after concussion.
- Current findings suggest that FBA may not be a sensitive biomarker for detecting PCS in pediatric concussion at this time point.
- Further validation in larger cohorts is necessary to confirm these results and explore potential biomarkers for pediatric concussion outcomes.
Objective:
Posttraumatic headache (PTH) represents the most common acute and persistent postconcussive symptom (PCS) in children after concussion, yet there remains a lack of valid and objective biomarkers to facilitate risk stratification and early intervention in this patient population. Fixel-based analysis of diffusion-weighted imaging, which overcomes constraints of traditional diffusion tensor imaging analyses, can improve the sensitivity and specificity of detecting white matter changes postconcussion. The aim of this study was to investigate whole-brain and tract-based differences in white matter morphology, including fiber density (FD) and fiber bundle cross-section (FC) area in children with PCSs and PTH at 2 weeks after concussion.
Methods:
This prospective longitudinal study recruited children aged 5-18 years who presented to the emergency department of a tertiary pediatric hospital with a concussion sustained within the previous 48 hours. Participants underwent diffusion-weighted MRI at 2 weeks postinjury. Whole-brain white matter statistical analysis was performed at the level of each individual fiber population within an image voxel (fixel) to compute FD, FC, and a combined metric (FD and bundle cross-section [FDC]) using connectivity-based fixel enhancement. Tract-based Bayesian analysis was performed to examine FD in 23 major white matter tracts.
Results:
Comparisons of 1) recovered (n = 27) and symptomatic (n = 16) children, and those with 2) PTH (n = 13) and non-PTH (n = 30; overall mean age 12.99 ± 2.70 years, 74% male) found no fiber-specific white matter microstructural differences in FD, FC, or FDC at 2 weeks postconcussion, when adjusting for age and sex (family-wise error rate corrected p value > 0.05). Tract-based Bayesian analysis showed evidence of no effect of PTH on FD in 10 major white matter tracts, and evidence of no effect of recovery group on FD in 3 white matter tracts (Bayes factor < 1/3).
Conclusions:
Using whole-brain fixel-wise and tract-based analyses, these findings indicate that fiber-specific properties of white matter microstructure are not different between children with persisting PCSs compared with recovered children 2 weeks after concussion. These data extend the limited research on white matter fiber-specific morphology while overcoming limitations inherent to traditional diffusion models. Further validation of our findings with a large-scale cohort is warranted.
