Ross, Katherine

Introduction Although migraine and persistent post-traumatic headache often share phenotypic characteristics, few studies have interrogated the pathophysiological differences underlying these headache types. While there is now some indication of differences in brain structure between migraine and persistent post-traumatic headache, differences in brain function have not been adequately investigated. The objective of this study was to compare static and dynamic functional connectivity patterns in migraine versus persistent post-traumatic headache using resting-state magnetic resonance imaging. Methods This case-control study interrogated the static functional connectivity and dynamic functional connectivity patterns of 59 a priori selected regions of interest involved in pain processing. Pairwise connectivity (region of interest to region of interest) differences between migraine (n = 33) and persistent post-traumatic headache (n = 44) were determined and compared to healthy controls (n = 36) with ANOVA and subsequent t-tests. Pearson partial correlations were used to explore the relationship between headache burden (headache frequency; years lived with headache) and functional connectivity and between pain intensity at the time of imaging and functional connectivity for migraine and persistent post-traumatic headache groups, separately. Results Significant differences in static functional connectivity between migraine and persistent post-traumatic headache were found for 17 region pairs that included the following regions of interest: Primary somatosensory, secondary somatosensory, posterior insula, hypothalamus, anterior cingulate, middle cingulate, temporal pole, supramarginal gyrus, superior parietal, middle occipital, lingual gyrus, pulvinar, precuneus, cuneus, somatomotor, ventromedial prefrontal cortex, and dorsolateral prefrontal cortex. Significant differences in dynamic functional connectivity between migraine and persistent post-traumatic headache were found for 10 region pairs that included the following regions of interest: Secondary somatosensory, hypothalamus, middle cingulate, temporal pole, supramarginal gyrus, superior parietal, lingual gyrus, somatomotor, precentral, posterior cingulate, middle frontal, fusiform gyrus, parieto-occiptal, and amygdala. Although there was overlap among the regions demonstrating static functional connectivity differences and those showing dynamic functional connectivity differences between persistent post-traumatic headache and migraine, there was no overlap in the region pair functional connections. After controlling for sex and age, there were significant correlations between years lived with headache with static functional connectivity of the right dorsolateral prefrontal cortex with the right ventromedial prefrontal cortex in the migraine group and with static functional connectivity of right primary somatosensory with left supramarginal gyrus in the persistent post-traumatic headache group. There were significant correlations between headache frequency with static functional connectivity of left secondary somatosensory with right cuneus in the migraine group and with static functional connectivity of left middle cingulate with right pulvinar and right posterior insula with left hypothalamus in the persistent post-traumatic headache group. Dynamic functional connectivity was significantly correlated with headache frequency, after controlling for sex and age, in the persistent post-traumatic headache group for one region pair (right middle cingulate with right supramarginal gyrus). Dynamic functional connectivity was correlated with pain intensity at the time of imaging for the migraine cohort for one region pair (right posterior cingulate with right amygdala). Conclusions Resting-state functional imaging revealed static functional connectivity and dynamic functional connectivity differences between migraine and persistent post-traumatic headache for regions involved in pain processing. These differences in functional connectivity might be indicative of distinctive pathophysiology associated with migraine versus persistent post-traumatic headache.

Objectives Often, persistent post-traumatic headache and migraine are phenotypically similar. However, the similarities and differences in the neuropathological underpinnings of persistent post-traumatic headache and migraine require further understanding. We used diffusion tensor imaging (DTI) and a novel method for detecting subtle changes in fibertract integrity by measuring node-by-node parameters along each tract to compare fibertract profiles between those with migraine and those with persistent post-traumatic headache, and compared both cohorts to a group of controls. Methods Eighteen fibertracts were reconstructed for 131 subjects, including 49 patients with persistent post-traumatic headache attributed to mild traumatic brain injury, 41 with migraine, and 41 controls. Node-by-node diffusion parameters of mean diffusivity and radial diffusivity were calculated along each tract. Mean diffusivity and radial diffusivity measurements were averaged along quartiles of each tract for statistical interpretation and group comparison. Using a post-hoc analysis, correlations between tract quartile measurements and headache frequency were calculated. Results There were significant differences between migraine and persistent post-traumatic headache cohorts for quartile measurements of mean diffusivity or radial diffusivity in the bilateral anterior thalamic radiations, cingulum (angular bundles and cingulate gyri), inferior longitudinal fasciculi, and uncinate fasciculi, the left corticospinal tract, and the right superior longitudinal fasciculi-parietal portion. For migraine patients, there was a significant positive correlation between headache frequency and forceps major mean diffusivity, whereas for persistent post-traumatic headache there was a positive correlation between headache frequency and cingulum angular bundle mean diffusivity and radial diffusivity. Conclusions Quartile measurements of radial diffusivity and mean diffusivity indicate unique differences in fibertract profiles between those with migraine vs. persistent post-traumatic headache. Although for both migraine and persistent post-traumatic headache there was a positive relationship between fibertract alterations and headache frequency, there were disease-specific differences between headache frequency and fibertract injury patterns. These findings might suggest potential differences in the neuropathological mechanisms underlying migraine and persistent post-traumatic headache.

Background Most persistent posttraumatic headaches (PPTH) have a phenotype that meets diagnostic criteria for migraine or probable migraine. Although symptoms of autonomic dysfunction have been well described among those with migraine, the presence and relative severity of such symptoms among those with PPTH have yet to be reported. Objective The objective of this study was to assess and compare symptoms of autonomic dysfunction among those with PPTH attributed to mild traumatic brain injury (mTBI) vs migraine vs healthy controls using Composite Autonomic Symptom Score 31 (COMPASS‐31) questionnaire scores. Methods Individuals with PPTH (n = 56) (87.5% of whom had a migraine/probable migraine phenotype), migraine (n = 30), and healthy controls (n = 36) were prospectively assessed in this cross‐sectional cohort study using the COMPASS‐31 questionnaire. Total COMPASS‐31 scores and individual domain scores (bladder, gastrointestinal, orthostatic intolerance, pupillomotor, secretomotor, vasomotor) were compared between subject groups. Results COMPASS‐31 mean total weighted score was 37.22 ± 15.44 in the PPTH group, 27.15 ± 14.37 in the migraine group, and 11.67 ± 8.98 for healthy controls. COMPASS‐31 mean weighted total scores were significantly higher in those with PPTH vs migraine ( P = .014), for PPTH vs healthy controls ( P = .001), and for migraine vs healthy controls ( P = .001). Those with PPTH had numerically higher scores for all COMPASS‐31 domains compared to those with migraine, and the domain scores were significantly higher for orthostatic intolerance (PPTH = 4.80 ± 2.47 vs migraine = 3.33 ± 2.31, P = .027) and bladder (PPTH = 1.14 ± 1.45 vs migraine = 0.47 ± 0.73, P = .020). Among individuals with PPTH, post hoc correlations indicated a positive association between number of total lifetime TBIs with total weighted COMPASS‐31 scores (rho = 0.32, P = .020), between years lived with headache and vasomotor domain subscores (rho = 0.27; P = .044), and between headache frequency with vasomotor domain subscores (rho = 0.27; P = .041). Conclusions Symptoms of autonomic dysfunction were greatest among those with PPTH compared to migraine and healthy controls. Among individuals with PPTH, number of lifetime TBIs was associated with greater symptoms of autonomic dysfunction, while greater headache burden was associated with higher vasomotor domain autonomic dysfunction subscores, potentially indicating that PPTH patients with higher disease burden have an increased risk for having autonomic dysfunction. Symptoms of autonomic dysfunction should be ascertained during the clinical management of patients with PPTH and might be a characteristic that helps differentiate PPTH from migraine.

Objective To investigate differences in cortical thickness in patients with persistent post‐traumatic headache (PPTH) relative to healthy controls and to interrogate whether cortical morphology relates to headache burden (headache frequency, years with post‐traumatic headache, PTH) in patients with PPTH. Background PTHs are one of the most common symptoms following concussion. In some patients, PTHs continue for longer than three months and are classified as PPTH. This study has two main goals: (1) To delineate the neuropathology of PPTH, by interrogating differences in cortical thickness in patients with PPTH relative to healthy controls. (2) To interrogate potential associations between brain morphology and headache burden in patients with PPTH by examining whether cortical thickness relates to frequency of headaches or years lived with PTH. Methods Adults with PPTH diagnosed according to ICHD 3 beta diagnostic criteria and healthy controls underwent brain MRI on a 3 Tesla scanner. Vertex‐by‐vertex whole brain estimates of cortical thickness were automatically calculated using FreeSurfer v5.3. Differences in cortical thickness in patients with PPTH relative to healthy controls were determined using a general linear model design. Associations were explored between regional clusters where patients with PPTH showed cortical thickness differences compared with healthy controls with headache frequency and years lived with PPTH. Results This study included 33 patients with PPTH and 33 healthy control subjects (healthy controls: median age = 33.0, IQR = 15.5; patients with PPTH: median age = 36.0, IQR = 20.5; P = .56). Patients with PPTH had less cortical thickness relative to healthy controls in the left and right superior frontal, caudal middle frontal, and precentral cortex as well as less cortical thickness in the right supramarginal, right superior and inferior parietal, and right precuneus region ( P < .05, Monte Carlo corrected for multiple comparisons). There were no regions where patients with PPTH had more cortical thickness relative to healthy controls. A correlation analysis of regions that showed less cortical thickness in patients with PPTH demonstrated a negative correlation between left and right superior frontal thickness with headache frequency ( P < .05). There was no association between regional cortical thickness and years lived with PPTH. Conclusion Compared with healthy controls, patients with PPTH had less cortical thickness in bilateral frontal regions and right hemisphere parietal regions. For patients with PPTH, more frequent headaches were related to less thickness in the left and right superior frontal regions, potentially indicating that brain morphology changes in the superior frontal regions in patients with PPTH are modified by headache frequency.