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Identifying oxidized lipid mediators as prognostic biomarkers of chronic posttraumatic headache.

ABSTRACT: Chronic posttraumatic headache (PTH) is among the most common and disabling sequelae of traumatic brain injury (TBI). Current PTH treatments are often only partially effective and have problematic side effects. We previously showed in a small randomized trial of patients with chronic nontraumatic headaches that manipulation of dietary fatty acids decreased headache frequency, severity, and pain medication use. Pain reduction was associated with alterations in oxylipins derived from n-3 and n-6 fatty acids, suggesting that oxylipins could potentially mediate clinical pain reduction. The objective of this study was to investigate whether circulating oxylipins measured in the acute setting after TBI could serve as prognostic biomarkers for developing chronic PTH. Participants enrolled in the Traumatic Head Injury Neuroimaging Classification Protocol provided serum within 3 days of TBI and were followed up at 90 days postinjury with a neurobehavioral symptom inventory (NSI) and satisfaction with life survey. Liquid chromatography-tandem mass spectrometry methods profiled 39 oxylipins derived from n-3 docosahexaenoic acid (DHA), and n-6 arachidonic acid and linoleic acid. Statistical analyses assessed the association of oxylipins with headache severity (primary outcome, measured by headache question on NSI) as well as associations between oxylipins and total NSI or satisfaction with life survey scores. Among oxylipins, 4-hydroxy-DHA and 19,20-epoxy-docosapentaenoate (DHA derivatives) were inversely associated with headache severity, and 11-hydroxy-9-epoxy-octadecenoate (a linoleic acid derivative) was positively associated with headache severity. These findings support a potential for DHA-derived oxylipins as prognostic biomarkers for development of chronic PTH.

SUBMITTER: Domenichiello AF

PROVIDER: S-EPMC7669546 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceThe Four Corners Youth Consortium was created to fill the gap in our understanding of youth concussion. This study is the first analysis of posttraumatic headache (PTH) phenotype and prognosis in this cohort of concussed youth.ObjectiveTo describe the characteristics of youth with PTH and determine whether the PTH phenotype is associated with outcome.Design, setting, and participantsThis cohort study examined outcomes from patients in a multi-institutional registry of traumatic brain injury (TBI) clinics from December 2017 to June 2019. Inclusion criteria included being between ages 5 and 18 years at enrollment and presentation within 8 weeks of a mild TBI. Data were analyzed between February 2019 and January 2021.ExposureMild TBI with standard care.Main outcomes and measuresTime to recovery and headache 3 months after injury; measurement device is the Postconcussion Symptom Inventory (PCSI). PTH with migraine phenotype was defined as moderate-severe headache that is new or significantly worse compared with baseline and associated with nausea and/or photophobia and phonophobia.ResultsA total of 612 patients with 625 concussions were enrolled, of whom 387 patients with 395 concussions consented to participate in this study. One hundred nine concussions were excluded (concussions, rather than patients, were the unit of analysis), leaving 281 participants with 286 concussions (168 [58.7%] girls; 195 [75.6%] White; 238 [83.2%] aged 13-18 years). At the initial visit, 133 concussions (46.5%) were from patients experiencing PTH with a migraine phenotype, 57 (20%) were from patients experiencing PTH with a nonmigraine phenotype, and 96 (34%) were from patients with no PTH. Patients with any PTH after concussion were more likely to have prolonged recovery than those without PTH (median [interquartile range], 89 [48-165] days vs 44 [26-96] days; log-rank P < .001). Patients with PTH and a migraine phenotype took significantly longer to recover than those with nonmigraine phenotype (median [interquartile range], 95 [54-195] days vs 70 [46-119] days; log-rank P = .01). Within each phenotype, there was no significant difference between sexes in recovery or PTH at 3 months.Conclusions and relevancePTH with a migraine phenotype is associated with persistent symptoms following concussion compared with nonmigraine PTH or no PTH. Given that female sex is associated with higher rates of migraine and migraine PTH, our finding may be one explanation for findings in prior studies that girls are at higher risk for persistent postconcussion symptoms than boys.

Project description:ImportanceHeadache is the most common symptom after pediatric concussion.ObjectivesTo examine whether posttraumatic headache phenotype is associated with symptom burden and quality of life 3 months after concussion.Design, setting, and participantsThis was a secondary analysis of the Advancing Concussion Assessment in Pediatrics (A-CAP) prospective cohort study, conducted September 2016 to July 2019 at 5 Pediatric Emergency Research Canada (PERC) network emergency departments. Children aged 8.0-16.99 years presenting with acute (<48 hours) concussion or orthopedic injury (OI) were included. Data were analyzed from April to December 2022.ExposurePosttraumatic headache was classified as migraine or nonmigraine headache, or no headache, using modified International Classification of Headache Disorders, 3rd edition, diagnostic criteria based on self-reported symptoms collected within 10 days of injury.Main outcomes and measuresSelf-reported postconcussion symptoms and quality-of-life were measured at 3 months after concussion using the validated Health and Behavior Inventory (HBI) and Pediatric Quality of Life Inventory-Version 4.0 (PedsQL-4.0). An initial multiple imputation approach was used to minimize potential biases due to missing data. Multivariable linear regression evaluated the association between headache phenotype and outcomes compared with the Predicting and Preventing Postconcussive Problems in Pediatrics (5P) clinical risk score and other covariates and confounders. Reliable change analyses examined clinical significance of findings.ResultsOf 967 enrolled children, 928 (median [IQR] age, 12.2 [10.5 to 14.3] years; 383 [41.3%] female) were included in analyses. HBI total score (adjusted) was significantly higher for children with migraine than children without headache (estimated mean difference [EMD], 3.36; 95% CI, 1.13 to 5.60) and children with OI (EMD, 3.10; 95% CI, 0.75 to 6.62), but not children with nonmigraine headache (EMD, 1.93; 95% CI, -0.33 to 4.19). Children with migraine were more likely to report reliable increases in total symptoms (odds ratio [OR], 2.13; 95% CI, 1.02 to 4.45) and somatic symptoms (OR, 2.70; 95% CI, 1.29 to 5.68) than those without headache. PedsQL-4.0 subscale scores were significantly lower for children with migraine than those without headache only for physical functioning (EMD, -4.67; 95% CI, -7.86 to -1.48).Conclusions and relevanceIn this cohort study of children with concussion or OI, those with posttraumatic migraine symptoms after concussion had higher symptom burden and lower quality of life 3 months after injury than those with nonmigraine headache. Children without posttraumatic headache reported the lowest symptom burden and highest quality of life, comparable with children with OI. Further research is warranted to determine effective treatment strategies that consider headache phenotype.

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Identifying oxidized lipid mediators as prognostic biomarkers of chronic posttraumatic headache.

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