Capillary blood protein markers of posttraumatic headache in children after concussion
Feiven Fan1,2, Franz E Babl1,3,4,5, Ella E K Swaney1,3
11Murdoch Children's Research Institute, Melbourne, Victoria.
Insights
No blood protein markers predict persistent posttraumatic headache (PTH) in children after concussion. This study found no specific signature in capillary blood to identify children at risk of PTH at 2 weeks postinjury.
Area of Science:
- Pediatric neurology
- Traumatic brain injury research
- Proteomics and biomarker discovery
Background:
- Posttraumatic headache (PTH) is a common symptom following concussion in children.
- Current methods lack objective biomarkers to predict persistent PTH, hindering early intervention.
- Identifying reliable blood protein signatures is crucial for risk stratification.
Purpose of the Study:
- To identify capillary blood protein markers for predicting persistent PTH in children within 48 hours of concussion.
- To stratify risk for early intervention in pediatric concussion management.
- To discover novel blood biomarkers for PTH prediction.
Main Methods:
- Collected capillary blood from children (8-17 years) presenting to the ED within 48 hours of concussion.
- Utilized untargeted proteomics with data-independent acquisition (DIA) on 907 identified proteins.
- Followed up participants at 2 weeks to assess PTH status.
Main Results:
- No specific blood protein signature was found to predict PTH at 2 weeks postinjury.
- Five proteins (HBZ, CSTB, CNDP1, HBG1, ZYX) showed weak associations with PTH, but lacked statistical significance.
- Eighty percent of participants had acute PTH, and one-third experienced PTH at 2-week follow-up.
Conclusions:
- Capillary blood protein analysis at ED presentation cannot predict persistent PTH in children post-concussion.
- Further research is urgently needed to discover reliable blood biomarkers for PTH risk stratification.
- Improved clinical management of pediatric concussion relies on identifying predictive biomarkers.
Objective:
Posttraumatic headache (PTH) represents the most common acute and persistent symptom in children after concussion, yet there is no blood protein signature to stratify the risk of PTH after concussion to facilitate early intervention. This discovery study aimed to identify capillary blood protein markers, at emergency department (ED) presentation within 48 hours of concussion, to predict children at risk of persisting PTH at 2 weeks postinjury.
Methods:
Capillary blood was collected using the Mitra Clamshell device from children aged 8-17 years who presented to the ED of the Royal Children's Hospital, Melbourne, Australia, within 48 hours of sustaining a concussion. Participants were followed up at 2 weeks postinjury to determine PTH status. PTH was defined per clinical guidelines as a new or worsened headache compared with preinjury. An untargeted proteomics analysis using data-independent acquisition (DIA) was performed. Principal component analysis and hierarchical clustering were used to reduce the dimensionality of the protein dataset.
Results:
A total of 907 proteins were reproducibly identified from 82 children within 48 hours of concussion. The mean participant age was 12.78 years (SD 2.54 years, range 8-17 years); 70% of patients were male. Eighty percent met criteria for acute PTH in the ED, while one-third of participants with follow-up experienced PTH at 2 weeks postinjury (range 8-16 days). Hemoglobin subunit zeta (HBZ), cystatin B (CSTB), beta-ala-his dipeptidase (CNDP1), hemoglobin subunit gamma-1 (HBG1), and zyxin (ZYX) were weakly associated with PTH at 2 weeks postinjury based on up to a 7% increase in the PTH group despite nonsignificant Benjamini-Hochberg adjusted p values.
Conclusions:
This discovery study determined that no capillary blood protein markers, measured at ED presentation within 48 hours of concussion, can predict children at risk of persisting PTH at 2 weeks postinjury. While HBZ, CSTB, CNDP1, HBG1, and ZYX were weakly associated with PTH at 2 weeks postinjury, there was no specific blood protein signature predictor of PTH in children after concussion. There is an urgent need to discover new blood biomarkers associated with PTH to facilitate risk stratification and improve clinical management of pediatric concussion.
