The prevalence of persistent post-traumatic headache in adult civilian traumatic brain injury: a systematic review and meta-analysis on the past 14 years

Headache is the most common type of pain following mild traumatic brain injury. Roughly half of those with persistent post-traumatic headache (PPTH) also report neck pain which is associated with greater severity and functional impact of headache. This observational cohort study aimed to identify biological phenotypes to help inform mechanism-based approaches in the management of PPTH with and without concomitant neck pain. Thirty-three military Veterans (mean (SD) = 37±16 years, 29 males) with PPTH completed a clinical assessment, quantitative sensory testing, and magnetic resonance imaging of the brain and cervical spine. Multidimensional phenotyping was performed using a Random Forest analysis and Partitioning Around Medoids (PAM) clustering of input features from three biologic domains: 1) resting state functional connectivity (rsFC) of the periaqueductal gray (PAG), 2) quality and size of cervical muscles, and 3) mechanical pain sensitivity and central modulation of pain. Two subgroups were distinguished by biological features that included forehead pressure pain threshold and rsFC between the PAG and selected nodes within the default mode, salience, and sensorimotor networks. Compared to the High Pain Coping group, the Low Pain Coping group exhibited higher pain-related anxiety (p=0.009), higher pain catastrophizing (p=0.004), lower pain self-efficacy (p=0.010), and greater headache-related disability (p=0.012). Findings suggest that greater functional connectivity of pain modulation networks involving the PAG combined with impairments in craniofacial pain sensitivity, but not cervical muscle health, distinguish a clinically important subgroup of individuals with PPTH who are less able to cope with pain and more severely impacted by headache.

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Differences in Eotaxin Serum Levels between Polytraumatized Patients with and without Concomitant Traumatic Brain Injury—A Matched Pair Analysis

Negrin,

Ristl,

Wollner

et al. 2024

JCM

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Background/Objectives: Early detection of traumatic brain injury (TBI) is crucial for minimizing secondary neurological damage. Our study aimed to assess the potential of IL-4, IL-6, IL-7, IL-8, IL-10, TNF, and eotaxin serum levels—as a single clinical tool or combined into a panel—for diagnosing TBI in multiple injured patients. Methods: Out of 110 prospectively enrolled polytrauma victims (median age, 39 years; median ISS, 33; 70.9% male) admitted to our level I trauma center over four years, we matched 41 individuals with concomitant TBI (TBI cohort) to 41 individuals without TBI (non-TBI cohort) based on age, gender, Injury Severity Score (ISS), and mortality. Patients’ protein levels were measured upon admission (day 0) and on days 1, 3, 5, 7, and 10 during routine blood withdrawal using one separation gel tube each time. Results: The median serum levels of IL-4, IL-6, IL-7, IL-8, IL-10, and TNF exhibited non-similar time courses in the two cohorts and showed no significant differences on days 0, 1, 3, 5, and 7. However, the median eotaxin levels had similar trend lines in both cohorts, with consistently higher levels in the TBI cohort, reaching significance on days 0, 3, and 5. In both cohorts, the median eotaxin level significantly decreased from day 0 to day 1, then significantly increased until day 10. We also found a significant positive association between day 0 eotaxin serum levels and the presence of TBI, indicating that for every 20 pg/mL increase in eotaxin level, the odds of a prevalent TBI rose by 10.5%. ROC analysis provided a cutoff value of 154 pg/mL for the diagnostic test (sensitivity, 0.707; specificity, 0.683; AUC = 0.718). Conclusions: Our findings identified the brain as a significant source, solely of eotaxin release in humans who have suffered a TBI. Nevertheless, the eotaxin serum level assessed upon admission has limited diagnostic value. IL-4, IL-6, IL-7, IL-8, IL-10, and TNF do not indicate TBI in polytraumatized patients.

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The prevalence of persistent post-traumatic headache in adult civilian traumatic brain injury: a systematic review and meta-analysis on the past 14 years

Cited by 3 publications

References 98 publications

Serum neurofilament light chain, inflammatory markers, and kynurenine metabolites in patients with persistent post-concussion symptoms: A cohort study

Serum neurofilament light chain, inflammatory markers, and kynurenine metabolites in patients with persistent post-concussion symptoms: A cohort study

Biological markers of brain network connectivity and pain sensitivity distinguish low coping from high coping Veterans with persistent post-traumatic headache

Differences in Eotaxin Serum Levels between Polytraumatized Patients with and without Concomitant Traumatic Brain Injury—A Matched Pair Analysis

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