OnabotulinumtoxinA for Pediatric Migraine.

BACKGROUND: Migraine is a painful, prevalent, and problematic condition among children. Children need access to safe and effective treatment options to alleviate the impact of this chronic condition on their wellbeing. CLINICAL IMPLICATIONS: Nurses have a crucial role in supporting patient access to BTX-A. Given the results of this and other studies demonstrating the safety and efficacy of BTX-A in children, nurses can support policy change for health plans to fund this intervention for pediatric migraineurs. Allowing children to receive the safe and effective BTX-A injections will lessen the already significant impact of chronic migraine on their physical, emotional and mental health. Nurses can also play a key role in providing education to patients regarding safe administration of BTX-A for migraine. AIM: The objective of this study was to define the experiences, effects, and clinical response of children to onabotulinumtoxinA (BTX-A) for migraine prevention. METHODS: Clinical documentation for patients aged 13-17 years presenting for BTX-A treatment for chronic migraine between 2016-2022 in a community-based specialty clinic within a large, urban, pediatric academic medical center were included. A series of one-way repeated measures (analysis of variance [ANOVA]) were conducted to compare headache frequency, severity, and duration at baseline, and following first and second injections of BTX-A. RESULTS: Of 32 eligible participants, administration of BTX-A demonstrated a decrease in headache frequency and severity. Participants reported nearly seven fewer headache days per month. Participants reported neck stiffness, fever or flu-like symptoms, fatigue, and worsening pain following BTX-A administration. CONCLUSIONS: Pediatric migraineurs need therapies that are safe, effective, and accessible. BTX-A was a safe and effective treatment for migraine among the children included in this study.

Alterations in the structure and function of the brain in adolescents with new daily persistent headache: A pilot MRI study.

OBJECTIVE: The purpose of this study was to explore brain morphological and functional connectivity alterations in adolescents with new daily persistent headache (NDPH) compared to pain-free, healthy controls. BACKGROUND: NDPH is one of the most disabling and least understood primary headache conditions. To date, no studies have considered the role of brain function and structure in pediatric patients with NDPH. METHODS: In this cross-sectional study, resting-state functional and structural images were acquired for 13 patients with NDPH (M age = 15.9, standard deviation [SD] ± 1.4) and 13 age- and sex-matched controls (M age = 16.2, SD ± 1.8) using magnetic resonance imaging. Participants were recruited from the Pediatric Headache Program at Boston Children's Hospital and from the Greater Boston area. In patients, clinical features of NDPH, including disease duration, pain intensity ratings, pain sensitivity, and functional disability were also assessed, and their associations with functional and structural brain alterations were explored. RESULTS: Compared to controls, patients with NDPH demonstrated reduced cortical thickness in the bilateral superior temporal gyrus, left superior, and middle frontal gyrus areas (p < 0.05, Monte Carlo corrected for multiple comparisons). Furthermore, reduced cortical thickness of the left superior frontal gyrus was related to elevated pain sensitivity in NDPH (r = -0.79, p = 0.006). Patients showed altered functional connectivity between regions involved in emotional and cognitive networks of pain, including the amygdala, insula, frontal regions, and cerebellar subregions. CONCLUSION: The present study provides the first preliminary evidence of functional and structural brain differences in pediatric patients with NDPH compared to controls. Identifying alterations in cortical thickness and resting-state connectivity between specific brain regions could provide characteristics of NDPH and probable mechanisms that may guide personalized therapeutic interventions.

Health Mindsets in Pediatric Chronic Headache.

OBJECTIVE: Given how frequently youth with chronic headache and migraine experience setbacks in treatment, identifying factors that promote coping and resilience is critical. Mindsets have gained attention as predictors of behavior and targets of intervention across contexts, including health. Health mindsets may help to explain how children with chronic pain interpret and respond to treatment. This study evaluated whether growth health mindsets might relate to adaptive outcomes in patients with chronic pediatric headache. METHODS: Participants were 88 children and adolescents (ages 10-17 years) with headache or migraine contacted following an appointment at a pediatric headache clinic, and their parent. Patients rated their beliefs about health as more fixed versus growth-oriented. They were presented with vignettes depicting hypothetical treatment setbacks and instructed to reflect upon real-life setbacks. Patients completed questionnaires about their cognitive appraisals of setbacks, coping, quality of life, life satisfaction, and functional impairment. RESULTS: The higher children rated their growth health mindsets, the less likely they were to appraise setbacks as threatening and endorse quality-of-life problems. Children with higher growth mindsets reported higher life satisfaction and lower functional disability. There was also an indirect relation between children's mindsets and coping through cognitive appraisals of setbacks as a threat, but not challenge. CONCLUSION: This research extends the health mindsets literature by contributing preliminary evidence of health mindsets as tied to adaptive outcomes in youth with chronic headache. These findings may be of interest to clinicians and parents, as health mindsets may offer an avenue by which resilience is promoted and maladaptive appraisals are minimized.

Shifting brain circuits in pain chronicity.

The evaluation of brain changes to a specific pain condition in pediatric and adult patients allows for insights into potential mechanisms of pain chronicity and possibly long-term brain changes. Here we focused on the primary somatosensory system (SS) involved in pain processing, namely the ventroposterolateral thalamus (VPL) and the primary somatosensory cortex (SI). We evaluated, using MRI, three specific processes: (a) somatotopy of changes in the SS for different pain origins (viz., foot vs. arm); (b) differences in acute (ankle sprain versus complex regional pain syndrome-CRPS); and (c) differences of the effects of CRPS on SS in pediatric versus adult patients. In all cases, age- and sex-matched individuals were used as controls. Our results suggest a shift in concurrent gray matter density (GMD) and resting functional connectivity strengths (rFC) across pediatric and adult CRPS with (a) differential patterns of GMD (VPL) and rFC (SI) on SS in pediatric vs. adult patterns that are consistent with upper and lower limb somatotopical organization; and (b) widespread GMD alterations in pediatric CRPS from sensory, emotional and descending modulatory processes to more confined sensory-emotional changes in adult CRPS and rFC patterns from sensory-sensory alterations in pediatric populations to a sensory-emotional change in adult populations. These results support the idea that pediatric and adult CRPS are differentially represented and may reflect underlying differences in pain chronification across age groups that may contribute to the well-known differences between child and adult pain vulnerability and resilience.

Age- and sex-related differences in the presentation of paediatric migraine: A retrospective cohort study.

Introduction Although migraine is a common headache complaint in children and adolescents there remains a significant gap in understanding the unique aspects of the disease in these age groups and their evolution with development. The aim of this retrospective cohort study was to identify migraine features that are influenced by age and sex. Methods The headache characteristics of 359 paediatric patients with a clinical diagnosis of migraine from a tertiary paediatric headache clinic were assessed. Patients retrospectively reported headache characteristics during a structured intake interview and clinical exam. Headache characteristics, description and associated symptoms were compared between children (age ≤ 12 years) and adolescents (age > 12 years), and between male and female migraineurs. Results Several migraine features differed significantly with age and/or sex, including: (i) a marked change from a 1:1 sex ratio in children to a 2:1 predominance of girls in adolescents; (ii) a higher frequency of headache attacks per month in adolescents and female migraineurs; (iii) a higher proportion of adolescents endorsed a 'throbbing' pain quality; (iv) a higher proportion of children reporting nausea and vomiting; and (v) a higher proportion of adolescents, particularly female migraineurs, had a diagnosis of a co-morbid anxiety. Conclusion The presentation of migraine, both in terms of its headache characteristics and associated symptoms, appear to vary as a function of age and sex. Given that migraine symptoms have a neural basis, it is not surprising that during the key period of neurodevelopment from childhood to adolescence this may impact their presentation.

Pediatric Headache and Sleep Disturbance: A Comparison of Diagnostic Groups.

OBJECTIVE: To examine whether sleep disturbance differs by headache diagnosis in a pediatric sample, and whether this effect remains when other factors affecting sleep are included. BACKGROUND: Primary headache disorders can be severe and disabling, impacting a child's functioning and quality of life. Many children and adolescents with chronic headaches also experience sleep difficulties, and there is likely a bidirectional relationship between headaches and sleep difficulties. Sleep problems may intensify functional and developmental difficulties in youth with chronic headaches. Despite this, research on sleep has largely been conducted only on those with migraines, with a dearth of studies including samples with tension-type headache (TTH) or new daily persistent-headache (NDPH). METHODS: This retrospective chart review included 527 patients, ages 7-17 years, with a primary headache diagnosis of migraine (n = 278), TTH (n = 157), and NDPH (n = 92). Patients completed measures of disability, anxiety, and depression and their parents completed measures of sleep disturbance. RESULTS: Sleep disturbance was greater in patients with TTH (10.34 ± 5.94, P = .002) and NDPH (11.52 ± 6.40, P < .001) than migraine (8.31 ± 5.89). Across patient groups, greater sleep disturbance was significantly associated with higher levels of functional disability (rs ≥ .16), anxiety (rs ≥ .30), and depression (rs ≥ .32). Additionally, higher pain levels were significantly associated with greater sleep disturbance among TTH patients (r = .23), with this association non-significant among the other headache groups. When simultaneously examining demographic, pain-related, and emotional distress factors, older age, higher levels of disability and depression, and NDPH diagnosis were all significant predictors of greater sleep disturbance (r2 = .25). CONCLUSIONS: Assessment and treatment of sleep problems in pediatric patients with chronic headache is important with several contextual and headache diagnostic factors influencing the severity of sleep disturbance.

Rapid Screening of Risk in Pediatric Headache: Application of the Pediatric Pain Screening Tool.

Objective: The current study examined the application of a screening tool to identify biopsychosocial risk factors and derive prognostic risk groups in children and adolescents with headache pain. Methods: Youth (n = 242, 8-17 years, 75.6% female) presenting for evaluation at a tertiary pediatric headache clinic completed the nine-item Pediatric Pain Screening Tool (PPST) as well as measures of functional disability, pain catastrophizing, fear of pain, anxiety, and depressive symptoms. In addition, 119 patients reported on functional disability at 2-month follow-up. Results: The PPST demonstrated discriminant validity that ranged from fair to good for identifying significant disability and high emotional distress. Receiver operating characteristic curve analyses indicated that established cutoff scores were appropriate for the current sample, and thus participants were classified into low-risk (21%), medium-risk (31%), and high-risk (48%) groups. Only 1-6% of patients who met reference standard case status for disability and emotional distress were classified as low risk, whereas 64-90% of patients who met reference standard case status were classified as high risk, suggesting robust stratification. Conclusions: The nine-item PPST may be a useful tool for efficiently identifying young patients with headache who are at risk of poor outcomes, and effectively classifying them into risk groups that could drive stratified treatment directly targeting patient needs.

In child and adult migraineurs the somatosensory cortex stands out again: An arterial spin labeling investigation.

Over the past decade, human brain imaging investigations have reported altered regional cerebral blood flow (rCBF) in the interictal phase of migraine. However, there have been conflicting findings across different investigations, making the use of perfusion imaging in migraine pathophysiology more difficult to define. These inconsistencies may reflect technical constraints with traditional perfusion imaging methods such as single-photon emission computed tomography and positron emission tomography. Comparatively, pseudocontinuous arterial spin labeling (pCASL) is a recently developed magnetic resonance imaging technique that is noninvasive and offers superior spatial resolution and increased sensitivity. Using pCASL, we have previously shown increased rCBF within the primary somatosensory cortex (S1) in adult migraineurs, where blood flow was positively associated with migraine frequency. Whether these observations are present in pediatric and young adult populations remains unknown. This is an important question given the age-related variants of migraine prevalence, symptomology, and treatments. In this investigation, we used pCASL to quantitatively compare and contrast blood flow within S1 in pediatric and young adult migraineurs as compared with healthy controls. In migraine patients, we found significant resting rCBF increases within bilateral S1 as compared with healthy controls. Furthermore, within the right S1, we report a positive correlation between blood flow value with migraine attack frequency and cutaneous allodynia symptom profile. Our results reveal that pediatric and young adult migraineurs exhibit analogous rCBF changes with adult migraineurs, further supporting the possibility that these alterations within S1 are a consequence of repeated migraine attacks. Hum Brain Mapp 38:4078-4087, 2017. © 2017 Wiley Periodicals, Inc.

Parental Attitudes About Placebo Use in Children.

OBJECTIVE: To assess parental attitudes regarding placebo use in pediatric randomized controlled trials and clinical care. STUDY DESIGN: Parents with children under age 18 years living in the US completed and submitted an online survey between September and November 2014. RESULTS: Among all 1300 participants, 1000 (76.9%; 538 mothers and 462 fathers) met the study inclusion criteria. The majority of surveyed parents considered the use of placebos acceptable in some pediatric care situations (86%) and some pediatric trials (91.5%), whereas only 5.7% of parents found the use of placebos in children always unacceptable. The clinical use of placebo was considered acceptable by a majority of parents for only 7 (mostly psychological) of the 17 conditions presented. Respondents' judgment about acceptability was influenced by the doctors' opinions about the therapeutic benefits of placebo treatment, the conditions for pediatric placebo use, transparency, safety, and purity of placebos. CONCLUSION: Most surveyed parents accepted the idea of using placebos in pediatric trials and within the clinic for some conditions without the practice of deception and with the creation of guidelines for ethical and safe use. This study suggests a need to reconsider pediatric trial design and clinical therapy in the light of generally positive parental support of appropriate placebo use.

Depression as a mediator of the relation between family functioning and functional disability in youth with chronic headaches.

OBJECTIVE: This retrospective chart review examined a mediation model of parent and family functioning, childhood depression, and functional disability in youth with chronic headaches. Specifically, we evaluated whether depression mediates the relations between protective parenting and functional disability and between family functioning and functional disability. BACKGROUND: Children and adolescents with chronic and recurrent headache report elevated symptoms of depression. Children with chronic pain conditions, including chronic headaches, have also been found to originate from families with greater conflict, poorer cohesion, and lower organizational structure, and impaired family functioning is associated with greater disability in youth with chronic pain. METHODS: Three hundred and eighty-two patients ages 5-17 years who underwent a multidisciplinary evaluation at a tertiary pediatric headache clinic were included in this study. Participants completed a pain intensity rating, the Children's Depression Inventory, and the Functional Disability Inventory. A parent completed the Family Relationship Index and the Adult Responses to Children's Symptoms questionnaires. Structural equation modeling was used to examine a mediation model and several alternative models. RESULTS: Mediation was not supported, but an alternative model with both direct and indirect pathways provided excellent fit to the data: χ2(1) = 0.745, P = .39; comparative fit index = 1.00, root mean square error of approximation = 0.00 (CI: 0.00-0.17). Family functioning (ß = -0.19, P < .01) and protective parenting (ß = 0.17, P < .01) were associated with depression, but not disability. Depression was linked to disability (ß = 0.24, P < .01). There was an indirect pathway from family functioning to depression to disability (ß = -0.05, P < .05). CONCLUSIONS: Family context is an important variable to consider in youth with chronic headaches and disability. While many studies have identified family functioning and depressive symptoms as separately linked to functional impairment, to our knowledge, we are the first to demonstrate depression as an intermediary variable between family dysfunction and disability within the pediatric headache population.

Autonomic dysfunction in pediatric patients with headache: migraine versus tension-type headache.

PURPOSE: To examine symptoms indicating central nervous system (CNS) autonomic dysfunction in pediatric patients with migraine and tension-type headache. METHODS: A retrospective chart review assessed six symptoms (i.e. constipation, insomnia, dizziness, blurry vision, abnormal blood pressure, and cold and clammy palms and soles) indicating central nervous system (CNS) autonomic dysfunction in 231 patients, ages 5-18 years, diagnosed with migraine, tension-type headache (TTH), or Idiopathic Scoliosis (IS). RESULTS: Higher frequencies of "insomnia," "dizziness," and "cold and clammy palms and soles" were found for both migraine and TTH patients compared to the IS control group (P < 0.001). Frequencies of all six symptoms were greater in TTH than migraine patients with "cold and clammy palms and soles" reaching significance (P < 0.001). CONCLUSIONS: The need for prospective research investigating autonomic dysfunction in pediatric headache patients is discussed.

Psychosis following traumatic brain injury and cannabis use in late adolescence.

BACKGROUND: Both cannabis and traumatic brain injury (TBI) pose risks on the developing brain, including a potential increased vulnerability for developing psychosis. Recent reports detail an upward trend in both adolescent cannabis use and the concentration of THC, the most potent psychoactive component in cannabis. Similarly, it is estimated that 1.7 million Americans incur a TBI each year. Previously trivialized as a minor nuisance, attitudes towards TBIs are changing as researchers and the public recognize TBIs' possible long-lasting sequelae. CASE REPORT: Two cases are presented of adolescent patients with histories of TBI and self-reported heavy, recreational cannabis use who developed symptoms of psychosis. DISCUSSION: Similar neuronal signaling pathways involved in cannabis ingestion and TBI recovery, specifically CB1 receptors of the endocannabinoid system, as well as the allostatic load model provide context for the two presented cases. Given the cases and theories presented, we believe that cannabis use may act as a neurological stressor and risk factor for psychosis outweighing its possible benefits as a therapeutic solution for pain in late adolescent and young adult populations. SIGNIFICANCE: The presented cases provide further support for the compounded risk of developing psychosis following TBI and cannabis use.

Fear of pain in pediatric headache.

OBJECTIVE: The current study provides the first measure of pain-related fear for pediatric headache patients. METHODS: From a large pediatric headache clinic, a cross-sectional cohort of 206 children and adolescents completed measures of pain-related fear, anxiety sensitivity, catastrophizing, pain acceptance, functional disability, and school functioning. RESULTS: The two-factor solution of the Fear of Pain Questionnaire (FOPQ) was confirmed from the originally derived structure with pediatric headache patients. Simultaneously regressing FOPQ subscales fear of pain and activity avoidance on theorized construct validity measures demonstrated that fear of pain was more closely linked with anxiety sensitivity and pain catastrophizing while activity avoidance had a strong negative association with pain acceptance (activity engagement and pain willingness). Pain-related fear was not significantly associated with pain level. After controlling for demographic factors and pain, fear of pain and activity avoidance accounted for an additional 26% of the variance in functional disability and school functioning outcomes, with activity avoidance accounting for much of this relationship. CONCLUSIONS: Although typically considered an influential construct among musculoskeletal patients, pain-related fear is also an important factor influencing functioning among pediatric headache patients, with the dimension of activity avoidance particularly salient.

Butalbital and pediatric headache: stay off the downward path.

Despite limited evidence from the literature surrounding safety or efficacy, butalbital-containing medicines (BCMs) have maintained their rank as "go-to" prescribed migraine and headache relief drugs in the United States, despite bans on these barbiturates in Germany and other European countries. Providers at the Pediatric Headache Program at Boston Children's Hospital recommend that clinicians prescribe triptan-based medications instead of BCMs, given the known negative side effects of BCMs on the general population, and the uncertain longitudinal trajectory of BCMs on developing brains.

"Pain Can't Stop Me": Examining Pain Self-Efficacy and Acceptance as Resilience Processes Among Youth With Chronic Headache.

OBJECTIVE: To examine pain self-efficacy and pain acceptance in relation to functioning in pediatric patients with chronic headache. METHODS: Participants were 209 youth aged 8-17 years who presented for a multidisciplinary pediatric headache clinic evaluation. They completed measures of pain self-efficacy and pain acceptance and a standard battery of clinical measures including indicators of emotional functioning. RESULTS: Pain self-efficacy and acceptance were associated with less disability, better school functioning, and fewer depressive symptoms. While taking into account several demographic and pain-related variables, pain self-efficacy had a greater association with less functional disability, while pain acceptance had a greater association with less depressive symptoms and better school functioning. CONCLUSIONS: These findings indicate that both resilience processes can serve to positively interact with functioning and symptoms of depression. Ultimately, this study suggests that higher levels of pain self-efficacy and pain acceptance in an individual experiencing pain are associated with more positive outcomes.

Habenula functional resting-state connectivity in pediatric CRPS.

The habenula (Hb) is a small brain structure located in the posterior end of the medial dorsal thalamus and through medial (MHb) and lateral (LHb) Hb connections, it acts as a conduit of information between forebrain and brainstem structures. The role of the Hb in pain processing is well documented in animals and recently also in acute experimental pain in humans. However, its function remains unknown in chronic pain disorders. Here, we investigated Hb resting-state functional connectivity (rsFC) in patients with complex regional pain syndrome (CRPS) compared with healthy controls. Twelve pediatric patients with unilateral lower-extremity CRPS (9 females; 10-17 yr) and 12 age- and sex-matched healthy controls provided informed consent to participate in the study. In healthy controls, Hb functional connections largely overlapped with previously described anatomical connections in cortical, subcortical, and brainstem structures. Compared with controls, patients exhibited an overall Hb rsFC reduction with the rest of the brain and, specifically, with the anterior midcingulate cortex, dorsolateral prefrontal cortex, supplementary motor cortex, primary motor cortex, and premotor cortex. Our results suggest that Hb rsFC parallels anatomical Hb connections in the healthy state and that overall Hb rsFC is reduced in patients, particularly connections with forebrain areas. Patients' decreased Hb rsFC to brain regions implicated in motor, affective, cognitive, and pain inhibitory/modulatory processes may contribute to their symptomatology.

Relations between pain characteristics, child and parent variables, and school functioning in adolescents with chronic headache: a comparison of tension-type headache and migraine.

OBJECTIVE: To assess for differences in headache characteristics and psychosocial factors based on headache diagnosis, and to evaluate whether headache diagnosis moderates relations between psychosocial factors and school difficulties. METHODS: Retrospective chart review was conducted with 262 adolescents with chronic tension-type headache (TTH; N = 153) and migraine evaluated at a pediatric headache clinic. Adolescents completed measures of anxiety, depression, and pain coping. Parents completed a measure of parental protective behavior and school functioning. RESULTS: Adolescents with TTH reported greater depression symptoms, and their parents endorsed greater school difficulties, whereas parents of adolescents with migraine reported more protective parenting. Protective parenting was positively associated with school difficulties in both groups, but the relation was significantly stronger in adolescents with TTH. Headache duration and depression symptoms were significant predictors of school functioning in both groups. CONCLUSIONS: Headache duration and depression may impact school functioning independent of headache diagnosis. Protective parenting, in particular, seems to be linked to school-related disability in adolescents with TTH, and this link may be important to consider in assessment and treatment.

Placebos in pediatrics: A cross-sectional survey investigating physicians' perspectives.

OBJECTIVE: Placebo responses are significantly higher in children than in adults, suggesting a potential underused treatment option in pediatric care. To facilitate the clinical translation of these beneficial effects, we explored physicians' current practice, opinions, knowledge, and likelihood of recommending placebos in the future. METHODS: A cross-sectional web-based survey administered by REDCap was conducted at Boston Children's Hospital between October 2021 and March 2022. Physicians (n = 1157) were invited to participate through an email containing a link to a 23-item survey designed to assess physicians' attitudes and perceptions towards the clinical use of placebo in pediatrics. RESULTS: From 207 (18%) returned surveys, 109 (9%) were fully completed. Most respondents (79%) believed that enhancing the therapeutic components that contribute to the placebo response may be a way of improving pediatric care. However, whereas most (62%) found placebo treatments permissible, only one-third reported recommending them. In pediatrics, placebos are typically introduced as a medicine that "might help" (43%). The most common treatments recommended to enhance placebo effects are physical therapy, vitamins, and over-the-counter analgesics. Physicians most frequently recommend placebos for occasional pain, headaches, and anxiety disorders. Finally, the great majority of physicians (87%) stated they would be more likely to recommend placebo treatments if there were safety and ethical guidelines for open-label placebos. CONCLUSIONS: Placebo treatments seem permissible to physicians in pediatric care, but the development of safety and ethical guidelines may be necessary before physicians systematically incorporate the benefits of the placebo effect in pediatrics.

Hippocampal volume changes across developmental periods in female migraineurs.

Brain-related plasticity can occur at a significant rate varying on the developmental period. Adolescence in particular has been identified as a period of growth and change across the structure and function of the nervous system. Notably, research has identified migraines as common in both pediatric and adult populations, but evidence suggests that the phenotype for migraines may differ in these cohorts due to the unique needs of each developmental period. Accordingly, primary aims of this study were to define hippocampal structure in females (7-27 years of age) with and without migraine, and to determine whether this differs across developmental stages (i.e., childhood, adolescence, and young adulthood). Hippocampal volume was quantified based on high-resolution structural MRI using FMRIB's Integrated Registration and Segmentation Tool. Results indicated that migraine and age may have an interactional relationship with hippocampal volume, such that, while hippocampal volumes were lower in female migraineurs (compared to age-matched controls) during childhood and adolescence, this contrast differed during young adulthood whereby hippocampal volumes were higher in migraineurs (compared to age-matched controls). Subsequent vertex analysis localized this interaction effect in hippocampal volume to displacement of the anterior hippocampus. The transition of hippocampal volume during adolescent development in migraineurs suggests that hippocampal plasticity may dynamically reflect components of migraine that change over the lifespan, exerting possible altered responsivity to stress related to migraine attacks thus having physiological expression and psychosocial impact.