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  • 1
    In: Pain Medicine, Oxford University Press (OUP), Vol. 22, No. 3 ( 2021-03-18), p. 670-676
    Abstract: Persistent posttraumatic headache (PPTH), one of the most common symptoms following mild traumatic brain injury, is often associated with substantial functional disability. The objective of this study was to assess the contribution of demographics, headache characteristics, and psychological symptoms to disability associated with PPTH. Methods Participants completed the State-Trait Anxiety Inventory (STAI), the Beck Depression Inventory (BDI), the Pain Catastrophizing Scale (PCS), and the Migraine Disability Assessment (MIDAS) questionnaire. Two linear regression models were formulated to interrogate the relationships between 1) demographics and headache characteristics with the MIDAS questionnaire and 2) demographics, headache characteristics, and psychological symptoms with the MIDAS questionnaire. A two-way stepwise regression using the Akaike information criterion was performed to find a parsimonious model describing the relationships between demographics, headache characteristics, and psychological measures with the MIDAS questionnaire. Results Participants included 58 patients with PPTH and 39 healthy controls (HCs). The median MIDAS score among those with PPTH was 48.0 (first quartile [1Q] = 20.0, third quartile [3Q] = 92.0), indicative of severe disability. Compared with the HCs, those with PPTH had higher scores on the BDI, STAI, and PCS. Older age predicted lower MIDAS scores (age: B=–0.11, P & lt;0.01), whereas higher headache frequency, greater headache intensity, and higher trait anxiety scores predicted higher MIDAS scores in individuals with PPTH (headache frequency: B=0.07, P & lt;0.001; headache intensity: B=0.51, P=0.04; trait anxiety score: B=1.11, P=0.01). Conclusions Individuals with PPTH had substantial psychological symptoms and headache-related disability. Disability was partially explained by age, headache frequency and intensity, and trait anxiety. Holistic management of patients with PPTH to address headaches and psychological symptoms might reduce headache-associated disability.
    Type of Medium: Online Resource
    ISSN: 1526-2375 , 1526-4637
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2023869-1
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  • 2
    In: Cephalalgia, SAGE Publications, Vol. 41, No. 8 ( 2021-07), p. 943-955
    Abstract: Persistent post-traumatic headache most commonly has symptoms that overlap those of migraine. In some cases, it can be clinically difficult to differentiate persistent post-traumatic headache with a migraine phenotype from migraine. The objective of this study was to develop a classification model based on questionnaire data and structural neuroimaging data that distinguishes individuals with migraine from those with persistent post-traumatic headache. Methods Questionnaires assessing headache characteristics, sensory hypersensitivities, cognitive functioning, and mood, as well as T1-weighted magnetic resonance imaging and diffusion tensor data from 34 patients with migraine and 48 patients with persistent post-traumatic headache attributed to mild traumatic brain injury were included for analysis. The majority of patients with persistent post-traumatic headache had a migraine/probable migraine phenotype (77%). A machine-learning leave-one-out cross-validation algorithm determined the average accuracy for distinguishing individual migraine patients from individual patients with persistent post-traumatic headache. Results Based on questionnaire data alone, the average classification accuracy for determining whether an individual person had migraine or persistent post-traumatic headache was 71.9%. Adding imaging data features to the model improved the classification accuracy to 78%, including an average accuracy of 97.1% for identifying individual migraine patients and an average accuracy of 64.6% for identifying individual patients with persistent post-traumatic headache. The most important clinical features that contributed to the classification accuracy included questions related to anxiety and decision making. Cortical brain features and fibertract data from the following regions or tracts most contributed to the classification accuracy: Bilateral superior temporal, inferior parietal and posterior cingulate; right lateral occipital, uncinate, and superior longitudinal fasciculus. A post-hoc analysis showed that compared to incorrectly classified persistent post-traumatic headache patients, those who were correctly classified as having persistent post-traumatic headache had more severe physical, autonomic, anxiety and depression symptoms, were more likely to have post-traumatic stress disorder, and were more likely to have had mild traumatic brain injury attributed to blasts. Discussion A classification model that included a combination of questionnaire data and structural imaging parameters classified individual patients as having migraine versus persistent post-traumatic headache with good accuracy. The most important clinical measures that contributed to the classification accuracy included questions on mood. Regional brain structures and fibertracts that play roles in pain processing and pain integration were important brain features that contributed to the classification accuracy. The lower classification accuracy for patients with persistent post-traumatic headache compared to migraine may be related to greater heterogeneity of patients in the persistent post-traumatic headache cohort regarding their traumatic brain injury mechanisms, and physical, emotional, and cognitive symptoms.
    Type of Medium: Online Resource
    ISSN: 0333-1024 , 1468-2982
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
    detail.hit.zdb_id: 2019999-5
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  • 3
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    Online Resource
    SAGE Publications ; 2022
    In:  Cephalalgia Vol. 42, No. 4-5 ( 2022-04), p. 357-365
    In: Cephalalgia, SAGE Publications, Vol. 42, No. 4-5 ( 2022-04), p. 357-365
    Abstract: Although iron accumulation in pain-processing brain regions has been associated with repeated migraine attacks, brain structural changes associated with post-traumatic headache have yet to be elucidated. To determine whether iron accumulation is associated with acute post-traumatic headache, magnetic resonance transverse relaxation rates (T2*) associated with iron accumulation were investigated between individuals with acute post-traumatic headache attributed to mild traumatic brain injury and healthy controls. Methods Twenty individuals with acute post-traumatic headache and 20 age-matched healthy controls underwent 3T brain magnetic resonance imaging including quantitative T2* maps. T2* differences between individuals with post-traumatic headache versus healthy controls were compared using age-matched paired t-tests. Associations of T2* values with headache frequency and number of mild traumatic brain injuries were investigated using multiple linear regression in individuals with post-traumatic headache. Significance was determined using uncorrected p-value and cluster size threshold. Results Individuals with post-traumatic headache had lower T2* values compared to healthy controls in cortical (bilateral frontal, bilateral anterior and posterior cingulate, right postcentral, bilateral temporal, right supramarginal, right rolandic, left insula, left occipital, right parahippocampal), subcortical (left putamen, bilateral hippocampal) and brainstem regions (pons). Within post-traumatic headache subjects, multiple linear regression showed a negative association between T2* in the right inferior parietal/supramarginal regions and number of mild traumatic brain injuries and a negative association between T2* in bilateral cingulate, bilateral precuneus, bilateral supplementary motor areas, bilateral insula, right middle temporal and right lingual areas and headache frequency. Conclusions Acute post-traumatic headache is associated with iron accumulation in multiple brain regions. Correlations with headache frequency and number of lifetime mild traumatic brain injuries suggest that iron accumulation is part of the pathophysiology or a marker of mild traumatic brain injury and post-traumatic headache.
    Type of Medium: Online Resource
    ISSN: 0333-1024 , 1468-2982
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
    detail.hit.zdb_id: 2019999-5
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  • 4
    In: Headache: The Journal of Head and Face Pain, Wiley, Vol. 61, No. 5 ( 2021-05), p. 740-754
    Abstract: Prior studies have established an association between a history of abuse and the development of migraine. This cross‐sectional observational study explored the relationship between self‐reported abuse history with migraine‐related sensory hypersensitivity symptoms. Methods In total, 588 adult patients with migraine from the American Registry for Migraine Research completed questionnaires: Generalized Anxiety Disorder‐7, Patient Health Questionnaire‐2 for depression, Photosensitivity Assessment Questionnaire, Hyperacusis Questionnaire, and Allodynia Symptom Checklist. Using four binary screening questions, patients were asked to self‐report if they believed they had suffered emotional, physical, or sexual abuse in their lifetime. Differences in questionnaire scores between groups with and without a history of abuse were determined. Regression models adjusted for age, sex, and basic headache features analyzed the relationship between abuse history and sensory hypersensitivity symptoms. Moderation analysis explored the role of headache frequency in this relationship. Mediation analysis assessed the indirect (Mediated) effect (IE) of abuse on sensory hypersensitivity through depression or anxiety. Additional models analyzed relationships between sensory hypersensitivity symptoms and abuse subtypes or the number of abuse subtypes. Results Of 588 participants, 222 (38%) reported a history of abuse. Patients with a history of abuse reported statistically significantly greater average headache frequency (7.6 vs. 4.7 days, p  = 0.030). Patients with a history of abuse also reported higher average or median questionnaire scores: anxiety (7.6 vs. 4.7, p   〈  0.001, d  = 0.56), depression (1.7 vs. 1.3, p  = 0.009, d  = 0.24), photophobia (0.54 vs. 0.44, p   〈  0.001, d  = 0.32), hyperacusis (19.6 vs. 14.9, p   〈  0.001, d  = 0.49), ictal allodynia (6.0 vs. 3.0, p   〈  0.001, d  = 0.46), and interictal allodynia (1.0 vs. 0.0, p   〈  0.001, d  = 0.30). After controlling for patient age, sex and years lived with headache, abuse maintained a significant association with every sensory hypersensitivity measure. Headache frequency significantly moderated the relationship between a history of abuse with increased ictal allodynia ( p  = 0.036). Anxiety significantly mediated the relationships between abuse with photophobia (IE = 0.03, 95% CI = 0.01–0.04), hyperacusis (IE = 1.51, 95% CI = 0.91–2.24), ictal allodynia (IE = 0.02, 95% CI = 0.01–0.04), and interictal allodynia (IE = 0.02, 95% CI = 0.01–0.06). Depression significantly mediated the relationship between abuse with photophobia (IE = 0.02, 95% CI = 0.01–0.03) and with hyperacusis (IE = 0.45, 95% CI = 0.11–0.88). The association between the individual subtypes of abuse and the number of subtypes of abuse with sensory hypersensitivity symptoms varied. Conclusion A history of abuse is associated with greater migraine‐related sensory hypersensitivity symptoms. To reduce the impact of abuse on migraine symptoms, future studies should explore mechanistic connections between abuse and migraine‐associated symptoms.
    Type of Medium: Online Resource
    ISSN: 0017-8748 , 1526-4610
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2020316-0
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  • 5
    In: The Journal of Headache and Pain, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2022-12)
    Abstract: Migraine involves central and peripheral nervous system mechanisms. Erenumab, an anti-calcitonin gene-related peptide (CGRP) receptor monoclonal antibody with little central nervous system penetrance, is effective for migraine prevention. The objective of this study was to determine if response to erenumab is associated with alterations in brain functional connectivity and pain-induced brain activations. Methods Adults with 6–25 migraine days per month during a 4-week headache diary run-in phase underwent pre-treatment brain functional MRI (fMRI) that included resting-state functional connectivity and BOLD measurements in response to moderately painful heat stimulation to the forearm. This was followed by two treatments with 140 mg erenumab, at baseline and 4 weeks later. Post-treatment fMRI was performed 2 weeks and 8 weeks following the first erenumab treatment. A longitudinal Sandwich estimator analysis was used to identify pre- to post-treatment changes in resting-state functional connectivity and brain activations in response to thermal pain. fMRI findings were compared between erenumab treatment-responders vs. erenumab non-responders. Results Pre- and post-treatment longitudinal imaging data were available from 32 participants. Average age was 40.3 (+/− 13) years and 29 were female. Pre-treatment average migraine day frequency was 13.8 (+/− 4.7) / 28 days and average headache day frequency was 15.8 (+/− 4.4) / 28 days. Eighteen of 32 (56%) were erenumab responders. Compared to erenumab non-responders, erenumab responders had post-treatment differences in 1) network functional connectivity amongst pain-processing regions, including higher global efficiency, clustering coefficient, node degree, regional efficiency, and modularity, 2) region-to-region functional connectivity between several regions including temporal pole, supramarginal gyrus, and hypothalamus, and 3) pain-induced activations in the middle cingulate, posterior cingulate, and periaqueductal gray matter. Conclusions Reductions in migraine day frequency accompanying erenumab treatment are associated with changes in resting state functional connectivity and central processing of extracranial painful stimuli that differ from erenumab non-responders. Trial registration clinicaltrials.gov (NCT03773562).
    Type of Medium: Online Resource
    ISSN: 1129-2369 , 1129-2377
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2020168-0
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  • 6
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    Online Resource
    Springer Science and Business Media LLC ; 2020
    In:  The Journal of Headache and Pain Vol. 21, No. 1 ( 2020-12)
    In: The Journal of Headache and Pain, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2020-12)
    Abstract: Close associations between insomnia with other clinical factors have been identified in migraine, but there have been few studies investigating associations between insomnia and clinical factors in patients with persistent post-traumatic headache (PPTH). The study objective was to contrast the severity of insomnia symptoms in PPTH, migraine, and healthy controls, and to identify factors associated with insomnia in patients with PPTH vs. migraine. Methods In this cross-sectional cohort study, 57 individuals with PPTH attributed to mild traumatic brain injury, 39 with migraine, and 39 healthy controls were included. Participants completed a detailed headache characteristics questionnaire, the Migraine Disability Assessment Scale (MIDAS), Insomnia Severity Index (ISI), Hyperacusis Questionnaire (HQ), Allodynia Symptom Checklist, Photosensitivity Assessment Questionnaire, Beck Depression Inventory (BDI), State-Trait Anxiety Inventory, Post-Traumatic Stress Disorder (PTSD) checklist, Ray Auditory Verbal Learning Test, and the Trail Making Test A and B to assess headache characteristics, disability, insomnia symptoms, sensory hypersensitivities, and neuropsychological factors. Fisher’s test and one-way ANOVA or Tukey’s Honest Significant Difference were used to assess group differences of categorical and continuous data. Stepwise linear regression analyses were conducted to identify clinical variables associated with insomnia symptoms. Results Those with PPTH had significantly higher ISI scores (16.7 ± 6.6) compared to migraine patients (11.3 ± 6.4) and healthy controls (4.1 ± 4.8) ( p   〈   0.001). For those with PPTH, insomnia severity was most strongly correlated with the BDI (Spearman’s rho ( ρ ) = 0.634, p   〈   0.01), followed by Trait Anxiety ( ρ = 0.522, p   〈   0.01), PTSD ( ρ  = 0.505, p   〈   0.01), HQ ( ρ  = 0.469, p   〈   0.01), State Anxiety ( ρ  = 0.437, p   〈   0.01), and MIDAS scores ( ρ = 0.364, p   〈   0.01). According to linear regression models, BDI, headache intensity, and hyperacusis scores were significantly positively associated with insomnia severity in those with PPTH, while only delayed memory recall was negatively associated with insomnia severity in those with migraine. Conclusions Insomnia symptoms were more severe in those with PPTH compared to migraine and healthy control cohorts. Depression, headache intensity, and hyperacusis were associated with insomnia in individuals with PPTH. Future studies should determine the bidirectional impact of treating insomnia and its associated symptoms.
    Type of Medium: Online Resource
    ISSN: 1129-2369 , 1129-2377
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
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  • 7
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Neurology Vol. 98, No. 1 ( 2022-01-4), p. S5-S6
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 98, No. 1 ( 2022-01-4), p. S5-S6
    Abstract: The objective was to develop classification models differentiating persistent PTH (PPTH) and migraine using clinical data and MRI-based measures of brain structure and functional connectivity. Background PTH and migraine commonly have similar phenotypes. Furthermore, migraine is a risk factor for developing PTH, sometimes making it difficult to differentiate PTH from exacerbation of migraine symptoms. Design/Methods Thirty-four individuals with migraine without history of TBI and 48 individuals with mild TBI attributed to PPTH but without history of migraine or prior frequent tension type headache were included. Subjects completed questionnaires assessing headache characteristics, mood, sensory hypersensitivities and cognitive function and underwent MRI imaging during the same day. Clinical features and structural brain measures from T1-weighted imaging, diffusion tensor imaging and functional resting-state measures were included as potential variables. A classifier using ridge logistic regression of principal components (PC) was fit. Since PCs can hinder identification of significant variables in a model, a second regression model was fit directly to the data. In the non-PC based model, input variables were selected based on lowest t -test or chi-square p -value by modality. Average accuracy was calculated using leave-one-out cross validation. The importance of variables to the classifier were examined. Results The PC-based classifier achieved an average classification accuracy of 85%. The non-PC based classifier achieved an average classification accuracy of 74.4%. Both classifiers were more accurate at classifying migraine subjects than PPTH. The PC-based model incorrectly classified 9/48 (18.8%) PPTH subjects compared to 3/34 (8.8%) migraine patients, whereas the non-PC classifier incorrectly classed 16/48 (33.3%) vs 5/34 (14.7%) of migraine subjects. Important variables in the non-PC model included static and dynamic functional connectivity values, several questions from the Beck Depression Inventory, and worsening symptoms and headaches with mental activity. Conclusions Multivariate models including clinical characteristics, functional connectivity, and brain structural data accurately classify and differentiate PPTH vs migraine.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 8
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2021
    In:  The Journal of Headache and Pain Vol. 22, No. 1 ( 2021-12)
    In: The Journal of Headache and Pain, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2021-12)
    Abstract: Headache is one of the most common symptoms after concussion, and mild traumatic brain injury (mTBI) is a risk factor for chronic migraine (CM). However, there remains a paucity of data regarding the impact of mTBI on migraine-related symptoms and clinical course. Methods Of 2161 migraine patients who participated in the American Registry for Migraine Research between February 2016 and March 2020, 1098 completed questions assessing history of TBI (50.8%). Forty-four patients reported a history of moderate to severe TBI, 413 patients reported a history of mTBI. Patients’ demographics, headache symptoms and triggers, history of physical abuse, allodynia symptoms (ASC-12), migraine disability (MIDAS), depression (PHQ-2), and anxiety (GAD-7) were compared between migraine groups with ( n  = 413) and without ( n  = 641) a history of mTBI. Either the chi-square-test or Fisher’s exact test, as appropriate, was used for the analyses of categorical variables. The Mann-Whitney test was used for the analyses of continuous variables. Logistic regression models were used to compare variables of interest while adjusting for age, gender, and CM. Results A significantly higher proportion of patients with mTBI had CM (74.3% [307/413] vs. 65.8% [422/641] , P  = 0.004), had never been married or were divorced (36.6% [147/402] vs. 29.4% [187/636] , P  = 0.007), self-reported a history of physical abuse (24.3% [84/345] vs. 14.3% [70/491] , P   〈   0.001), had mild to severe anxiety (50.5% [205/406] vs. 41.0% [258/630] , P  = 0.003), had headache-related vertigo (23.0% [95/413] vs. 15.9% [102/640] , P  = 0.009), and difficulty finding words (43.0% [174/405] vs. 32.9% [208/633] , P   〈   0.001) in more than half their attacks, and headaches triggered by lack of sleep (39.4% [155/393] vs. 32.6% [198/607] , P  = 0.018) and reading (6.6% [26/393] vs. 3.0% [18/607] , P  = 0.016), compared to patients without mTBI. Patients with mTBI had significantly greater ASC-12 scores (median [interquartile range]; 5 [1–9] vs. 4 [1–7], P   〈  0.001), MIDAS scores (42 [18–85] vs. 34.5 [15–72] , P  = 0.034), and PHQ-2 scores (1 [0–2] vs. 1 [0–2] , P  = 0.012). Conclusion Patients with a history of mTBI are more likely to have a self-reported a history of physical abuse, vertigo, and allodynia during headache attacks, headaches triggered by lack of sleep and reading, greater headache burden and headache disability, and symptoms of anxiety and depression. This study suggests that a history of mTBI is associated with the phenotype, burden, clinical course, and associated comorbid diseases in patients with migraine, and highlights the importance of inquiring about a lifetime history of mTBI in patients being evaluated for migraine.
    Type of Medium: Online Resource
    ISSN: 1129-2369 , 1129-2377
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2020168-0
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  • 9
    In: The Journal of Headache and Pain, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2021-12)
    Abstract: Changes in speech can be detected objectively before and during migraine attacks. The goal of this study was to interrogate whether speech changes can be detected in subjects with post-traumatic headache (PTH) attributed to mild traumatic brain injury (mTBI) and whether there are within-subject changes in speech during headaches compared to the headache-free state. Methods Using a series of speech elicitation tasks uploaded via a mobile application, PTH subjects and healthy controls (HC) provided speech samples once every 3 days, over a period of 12 weeks. The following speech parameters were assessed: vowel space area, vowel articulation precision, consonant articulation precision, average pitch, pitch variance, speaking rate and pause rate. Speech samples of subjects with PTH were compared to HC. To assess speech changes associated with PTH, speech samples of subjects during headache were compared to speech samples when subjects were headache-free. All analyses were conducted using a mixed-effect model design. Results Longitudinal speech samples were collected from nineteen subjects with PTH (mean age = 42.5, SD = 13.7) who were an average of 14 days (SD = 32.2) from their mTBI at the time of enrollment and thirty-one HC (mean age = 38.7, SD = 12.5). Regardless of headache presence or absence, PTH subjects had longer pause rates and reductions in vowel and consonant articulation precision relative to HC. On days when speech was collected during a headache, there were longer pause rates, slower sentence speaking rates and less precise consonant articulation compared to the speech production of HC. During headache, PTH subjects had slower speaking rates yet more precise vowel articulation compared to when they were headache-free. Conclusions Compared to HC, subjects with acute PTH demonstrate altered speech as measured by objective features of speech production. For individuals with PTH, speech production may have been more effortful resulting in slower speaking rates and more precise vowel articulation during headache vs. when they were headache-free, suggesting that speech alterations were related to PTH and not solely due to the underlying mTBI.
    Type of Medium: Online Resource
    ISSN: 1129-2369 , 1129-2377
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2020168-0
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  • 10
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    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Neurology Vol. 94, No. 15_supplement ( 2020-04-14)
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 94, No. 15_supplement ( 2020-04-14)
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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