Post-traumatic Headache After Pediatric Traumatic Brain Injury: Prevalence, Risk Factors, and Association With Neurocognitive Outcomes.

Post-traumatic headache is common after pediatric traumatic brain injury and affects thousands of children every year, but little is known about how headache affects recovery after traumatic brain injury in other symptom domains. We aimed to determine the association between headache and other common symptoms after pediatric traumatic brain injury and explore whether subjective complaints of headache are associated with objective deficits on specialized neurocognitive testing. We conducted a retrospective cohort study of children ages 3-19 years following traumatic brain injury with a completed Sports Concussion Assessment Tool (SCAT) questionnaire. Post-traumatic headache was defined by a score more than 2 on the SCAT question for headache and define headache groups for comparison. In our cohort, we analyzed data from the Delis-Kaplan Executive Function System and the Wechsler Abbreviated Scale of Intelligence, Second Edition (WASI-II). Headache was reported in 40 (33%) patients presenting for post-traumatic brain injury care among 121 pediatric traumatic brain injury patients and did not differ by injury severity. Median total SCAT symptom score in the headache group was 5-fold higher compared to patients without headache (median 45.5 vs 9; P < .001). Significantly lower-scaled scores in color naming, matrix reasoning, letter sequencing, and letter switching were also found in the headache group (all P ≤ .03). Our study shows that headache, as reported by patients on the SCAT, is associated with higher symptom scores in all other symptom domains, including sleep, mood, sensory, and cognitive. Headache was also associated with worse objective neurocognitive measures and may identify patients who could benefit from specialized follow-up care and management.

Epithelial sodium channel is regulated by SNAP-23/syntaxin 1A interplay.

Sodium-selective amiloride-sensitive epithelial channel (ENaC) located in the apical membrane is involved in the reabsorption of sodium in tight epithelia. The soluble N-ethylmaleimide-sensitive attachment receptors (SNAREs) mediate vesicle trafficking in a variety of cell systems. Syntaxin (a t-SNARE) has been shown to interact with and functionally regulate a number of ion channels including ENaC. In this study, we investigated the role of SNAP-23, another SNARE protein, on ENaC activity in the HT-29 colonic epithelial cell system and Xenopus oocytes. Recording of amiloride-sensitive currents in both systems suggest that SNAP-23 modulates channel function, though a much higher concentration is required to inhibit ENaC in Xenopus oocytes. The introduction of Botulinum toxin A (a neurotoxin which cleaves SNAP-23), but not Botulinum toxin B or heat-inactivated Botulinum toxin A, reversed the inhibitory effect of SNAP-23 on amiloride-sensitive currents. However, syntaxin 1A and SNAP-23 combined portray a complex scenario that suggests that this channel interacts within a quaternary complex. Synaptotagmin expression neither interacts with, nor showed any effect on amiloride-sensitive currents when co-expressed with ENaC. Pull down assays suggest mild interaction between ENaC and SNAP-23, which gets stronger in the presence of syntaxin 1A. Data further suggest that SNAP-23 possibly interacts with the N-terminal alphaENaC. These functional and biochemical approaches provide evidence for a complex relationship between ENaC and the exocytotic machinery. Our data suggest that SNARE protein interplay defines the fine regulation of sodium channel function.