Starling, Amaal

Aim Post-traumatic headache (PTH) attributed to mild traumatic brain injury (mTBI) frequently co-occurs with other physical, cognitive, and emotional symptoms. This study assessed associations between PTH improvement and these symptoms in individuals with acute headaches (APTH) and compared symptoms between those who had recently developed persistent PTH (PPTH) to those who had long-standing PPTH. Methods This study included 105 individuals with APTH (mean age = 43.4, SD = 15.8; 70 females, 35 males) and 46 individuals with PPTH (mean age = 38.2, SD = 10.9; 16 females, 30 males) with an average duration of 11.3 years from two prospective longitudinal studies. For those who had APTH, PTH improvement was assessed at three months post-enrollment using an electronic headache diary. Participants completed questionnaires evaluating physical (including headache symptoms, photosensitivity, hyperacusis, insomnia, autonomic symptoms, and disability), emotional (including depression, anxiety, pain catastrophizing, and post-traumatic stress disorder screening), and cognitive symptoms (including memory and attention). The APTH cohort completed questionnaires at baseline, follow-up #1 (three to four months from baseline), and follow-up #2 (six to seven months from baseline). Mixed Effects Models were used to analyze the temporal trend of symptoms among the APTH improved and non-improved groups. Results Among the 105 individuals with APTH, 60 experienced PTH improvement and 45 did not. At baseline, compared to those who had PTH improvement, those who did not have PTH improvement had higher SCAT total scores and physical subscores, greater levels of hyperacusis, pain catastrophizing, anxiety and depression. At follow-up #1 (three to four months), these individuals continued to show more pronounced physical and emotional symptoms and worse cognitive function and insomnia. Most of these group differences persisted at follow-up #2 (six to seven months). Most symptoms showed progressive improvement over three months for individuals who had PTH improvement but not for those without PTH improvement. Furthermore, individuals with long-standing PPTH showed more severe insomnia, pain catastrophizing, and PTSD compared to those who had recently developed PPTH. Conclusion Individuals with APTH who did not experience PTH improvement at three months had more severe physical, cognitive, and emotional symptoms at baseline compared to those who had PTH improvement. While most symptoms normalized in individuals with PTH improvement, symptoms overall persisted at three and at six months for those with PTH persistence. Individuals who had long-standing PPTH had more severe insomnia and more negative cognitive/emotional responses to pain compared to those who had recently developed PPTH.

Abstract Background Post-traumatic headache (PTH) is a common acute and persistent symptom following mild traumatic brain injury (mTBI). Symptoms of cutaneous allodynia and presence of nociceptive sensitization might be associated with acute PTH and its persistence. The objectives of this study were to compare allodynia symptoms and cutaneous heat pain thresholds amongst males and females with acute PTH to healthy controls (HC) and determine if pain thresholds and allodynia symptoms are associated with PTH outcomes. Methods This prospective longitudinal study enrolled 139 adults with acute PTH attributed to mTBI as defined by the International Classification of Headache Disorders and 95 HC. All PTH participants completed a baseline research visit near PTH onset and a follow-up visit three to four months later. All PTH participants and a subset of HC completed the Allodynia Symptom Checklist (ASC-12) at each research visit. A different subset of the participants underwent quantitative sensory testing (QST) during baseline, 4-week, and 16-week research visits to quantify cutaneous heat pain thresholds at the forehead and forearms. Data from daily headache diaries were used to determine longitudinal PTH improvement versus non-improvement at three months. ASC-12 score and pain threshold comparisons were made between PTH and HC groups, PTH improved versus non-improved cohorts, and between PTH males and females. Results Participants with PTH had an average age of 42.6 years and 64.0% were female. HC had an average age of 40.0 years and 65.3% were female. At the first visit, PTH participant ASC-12 scores averaged 3.6 versus 0.1 amongst HC, p < 0.001. 44.8% of PTH participants had headache improvement at 3 months. ASC-12 scores were higher in the PTH non-improved versus improved group at baseline (4.0 versus 2.4, p = 0.038) and 3-month follow-up (3.4 versus 1.9, p = 0.012). ASC-12 scores were higher in females than males at baseline (4.7 versus 1.6, p < 0.001) and 3-months (3.9 versus 1.2, p < 0.001). Cutaneous heat pain thresholds at the forehead and forearm did not differ between any group. Conclusions PTH attributed to mTBI is associated with symptoms of cutaneous allodynia. Greater allodynia symptoms are present in females with PTH compared to males and may be associated with PTH non-improvement.

Background Headache is a common symptom following mild traumatic brain injury (mTBI). Post-traumatic headache (PTH), a secondary headache disorder that develops after mTBI, often persists for months or years. To identify potential recovery mechanisms and prognostic biomarkers, the present study investigated whether longitudinal changes in pain-induced brain activation differ between healthy controls (HC) and PTH participants showing headache improvement and those without improvement. Methods Thirty-three participants who met International Classification of Headache Disorders, 3rd edition, criteria for acute PTH within 59 days post-mTBI and 33 HC participants were included with no significant differences in demographics. All participants underwent functional magnetic resonance imaging scans at baseline, four weeks, and 16 weeks post-enrollment using a thermal stimulation paradigm with noxious and non-painful heat stimuli. ‘Painful vs. Non-Painful Heat’ contrasts were generated using SPM12. PTH improvement was assessed at three months post-enrollment via electronic headache diaries. Two-sample t -tests compared the brain activation between HC and PTH at baseline. Linear mixed-effects models examined longitudinal changes for HC, PTH improvement and non-improvement groups across visits. Generalized linear models compared these groups within visits. Results Baseline analysis revealed several regions with significantly higher activation in acute PTH compared to HC, including bilateral postcentral gyrus, right superior temporal gyrus, right middle temporal gyrus, left inferior parietal gyrus, right superior parietal gyrus, left ventral striatum, left olfactory cortex, left gyrus rectus, and left middle occipital gyrus. Over time, the PTH improvement group demonstrated progressive normalization across all identified brain regions, whereas the non-improvement group showed only partial normalization in left ventral striatum, left olfactory cortex, and left gyrus rectus. Sustained elevated activation in specific regions distinguished PTH participants without headache improvement from those with headache improvement, suggesting potential biomarkers for persistent PTH. Conclusions Our findings demonstrate significantly altered pain-induced brain activations in participants with acute PTH compared to HC. Longitudinal analysis revealed distinct recovery trajectories: progressive normalization in the improvement group versus persistent alterations in the non-improvement group. These neuroimaging patterns may serve as biomarkers for identifying individuals at risk for persistent PTH, with implications for early intervention and personalized treatment approaches.