Habitual caffeinated beverage consumption and headaches among adults with episodic migraine: A prospective cohort study.

OBJECTIVE: To examine the relationship between habitual caffeinated beverage consumption and headache frequency, duration, and intensity in a prospective cohort of adults with episodic migraine. BACKGROUND: Caffeine is a commonly ascribed headache trigger in adults with migraine and clinicians may counsel patients to avoid caffeinated beverages; however, few studies have examined this association. METHODS: From March 2016 to August 2017, 101 adults with physician-confirmed episodic migraine completed baseline questionnaires, including information about caffeinated beverage consumption. For 6 weeks, they reported headache onset, duration, and pain intensity (scale 0-100) on twice-daily electronic diaries. Ninety-seven participants completed data collection. We examined associations between self-reported habitual caffeinated beverage consumption at baseline and headache outcomes prospectively captured over the following 6 weeks, adjusting for age, sex, and oral contraceptive use. RESULTS: The adjusted mean headache days per month was similar among the 20 participants reporting no habitual intake (7.1 days, 95% confidence interval [CI] 5.1-9.2), the 65 participants reporting 1-2 servings/day (7.4 days, 95% CI 6.1-8.7), and the 12 participants reporting 3-4 servings/day (5.9 days, 95% CI 3.3-8.4). Similarly, mean headache duration (no servings/day: 8.6 h, 95% CI 3.8-13.3; 1-2 servings/day: 8.5 h, 95% CI 5.5-11.5; 3-4 servings/day: 8.8 h, 95% CI 2.3-14.9) and intensity (no servings/day: 43.8, 95% CI 37.0-50.5; 1-2 servings/day: 43.1, 95% CI 38.9-47.4; 3-4 servings/day: 46.5, 95% CI 37.8-55.3) did not differ across levels of caffeinated beverage intake, though estimates were imprecise. CONCLUSIONS: We found no association between habitual caffeinated beverage intake and headache frequency, duration, or intensity. These data do not support a recommendation that patients with episodic migraine should avoid consuming caffeine. Further research is needed to understand whether deviating from usual caffeine intake may trigger migraine attacks.

Sleep Symptoms in Migraine.

PURPOSE OF REVIEW: To review replicated and highlight novel studies of sleep in children and adults with episodic and chronic migraine. RECENT FINDINGS: Attack-related sleep symptoms are most common in the prodrome and may represent early activation of the hypothalamus rather than migraine triggers. Interictally, patients with migraine report poor sleep quality and high rates of insomnia symptoms. Cognitive behavioral therapy for insomnia in adults and adolescents with chronic migraine and comorbid insomnia results in significant improvement on their headache burden. Thus far, objective studies report that migraine per se is a not associated with sleep apnea. At the present time, there is minimal evidence that migraine is under circadian influence. The current body of evidence suggests that the insomnia symptoms and poor sleep quality commonly reported by patients with migraine are not attack-related but occur interictally and are a marker of worsening disease. The development of clinical guidelines to approach sleep symptoms and expansion of CBT-I trials in those with episodic migraine would be clinically valuable.

The Glymphatic System and its Relationship to Migraine.

PURPOSE OF REVIEW: We aim to critically review animal and human studies of the glymphatic system in migraine and propose a model for how the glymphatic system may function in migraine, based on the available evidence. RECENT FINDINGS: Early studies in animal models report migraine attacks temporarily disrupt glymphatic flow. Human imaging studies suggest chronic migraine may be associated with alterations in glymphatic system function, albeit with conflicting results. Presently, it remains unknown whether repetitive migraine attacks or frequent nights of insomnia impair glymphatic system function over time in those with migraine, and whether alterations in glymphatic function could contribute to worsening migraine disability or risk for cognitive disease. Longitudinal studies of glymphatic function in patients with migraine and insomnia, with inclusion of cognitive assessments, may be informative.

Sleep Symptoms and Disorders in Episodic Migraine: Assessment and Management.

PURPOSE OF REVIEW: We review research on sleep symptoms and disorders in patients with episodic migraine and propose a framework for evaluating sleep symptoms in this patient population. RECENT FINDINGS: Patients with episodic migraine consistently report poorer sleep on validated self-reports compared to those without migraine. In polysomnographic studies, children with migraine have objectively shorter sleep duration and lower percentage of REM sleep interictally. Prospective actigraphy studies in adults and children suggest that there are no significant changes in sleep duration, efficiency, or quality in the night before or after a migraine attack. The relationship between sleep and migraine is multifaceted. Patients with episodic migraine report poorer sleep and have higher risk of some sleep disorders, including insomnia, sleep-related bruxism, and restless legs syndrome. Sleep screening questions may be incorporated into headache evaluations. Care should be taken to avoid headache medications that may exacerbate sleep symptoms. Evidence-based treatments for insomnia may be initiated while patients await CBT-I. Further studies are needed to assess whether treatment of comorbid sleep disorders results in improvement in migraine-related burden in those with episodic migraine.

Addressing inequities in headache care by embedding services in a community health center in Boston, MA.

There is a critical need to diagnose and treat headache disorders in primary care settings. This is especially true for those who face systemic barriers to healthcare access due to racism or poverty. In order to target those at higher risk of disability associated with neurologic disease in our healthcare system, we embedded a specialized headache and neurology clinic within the Brigham and Women's Hospital Southern Jamaica Plain Community Health Center in Boston, MA. The goal was to create a sustainable, integrated clinic consistent with the CHC's racial justice mission, with an emphasis on equitable care, awareness of structural barriers to care, improved communication with primary care and inclusion of trainees as important members of a healthcare team. In its' first year, the clinic had over 400 patient visits, with a near-perfect rate of completion of consults. In addition to improved access to tertiary care headache services, successes have included improving continuity of care, cultivating a model of shared care with primary care practitioners and stimulating interest in headache medicine among staff and trainees. Challenges have included the use of staff time to complete prior authorizations, and the need to find or develop Spanish-language and culturally appropriate patient educational resources. By providing care within the patient's medical home, the headache specialist gains a deeper appreciation of a patient's social determinants of health and can readily access resources to navigate barriers. The personal and professional fulfillment that headache specialists may experience while doing this important work could help protect against burnout. Sustainability depends on ensuring equitable provider reimbursement; departmental and institutional support is essential. We believe this clinic can serve as a model for specialists throughout the United States who wish to improve the delivery of care to patient populations who face access barriers.

Baseline sleep quality, stress, and depressive symptoms, and subsequent headache occurrence in a six-week prospective cohort study of patients with episodic migraine.

OBJECTIVES/BACKGROUND: Despite the high prevalence of sleep disturbance, stress, and depressive symptoms among patients with episodic migraine, there has been limited prospective research examining how these comorbid symptoms relate to future headache risk. METHODS: We conducted an a priori secondary analysis of a prospective cohort study of 98 adults with episodic migraine recruited through Harvard-affiliated medical centers and local college student clinics in Boston, MA. At baseline, participants completed validated questionnaires on sleep quality, stress, and depressive symptoms. Over the next 6 weeks, they recorded headaches on twice-daily diaries. We conducted time-to-event analyses to evaluate whether these baseline symptoms were associated with headache recurrence. RESULTS: At baseline, 45/98 (46%) participants had poor sleep quality, 51/98 (52%) reported moderate/high stress levels, and 18/98 (18%) had high depressive symptom scores. Over 4,406 person-days, we observed 823 discrete headaches. In multivariable models, the hazard ratios for headache recurrence were: 1.22 (95% CI 1.02, 1.46) for people with baseline poor sleep, 1.12 (95% CI 0.93, 1.35) for those with baseline moderate/high stress compared to lower levels, and 1.31 (95% CI 1.05, 1.65) for the combination of poor sleep and moderate/high stress compared to the combination of good sleep and low stress. There was no association between depression scores and headache risk. CONCLUSION: Among patients with episodic migraine, poor sleep was associated with a higher rate of headache recurrence over the next 6 weeks, especially among those with coexisting moderate/high stress.

Prospective cohort study of routine exercise and headache outcomes among adults with episodic migraine.

OBJECTIVE: To evaluate the association of routine exercise with headache frequency, intensity, and duration among adults with episodic migraine (EM). BACKGROUND: A comprehensive management plan for EM must aim at reducing disability and cost of care; to do so requires optimizing acute and preventive medications, and behavior changes. Prophylactic medication use is associated with adverse events and contraindications with comorbidities. Aerobic exercise is reported to decrease migraine frequency. However, no study has evaluated a potential synergistic relation between regular exercise and preventive medication use among patients with EM. DESIGN AND METHODS: This was a secondary analysis of data from a prospective cohort study of adults with EMs. In that study, adults with EM (using International Classification of Headache Disorders-3 criteria confirmed by study physicians) were recruited from three academic medical centers in Boston, MA. At baseline, participants provided information on exercise, clinical and demographic characteristics, and lifestyle behaviors. We prospectively collected daily information on headaches and health behavior over at least 6 weeks using electronic questionnaires from 94 participants. We assessed the association between baseline self-reported moderate-vigorous exercise at least three times per week, at baseline, and prospectively recorded headache frequency, intensity, and duration. We further assessed whether these associations differed by the prevalent use of prophylactic migraine medication. RESULTS: Data from 94 of 98 eligible participants were used in the analysis as 4 participants had missing data on routine exercise frequency or intensity at baseline. On average, patients who reported moderate-vigorous exercise at least three times per week at enrollment had 1.5 fewer headache days per month (-1.5 headache days/month; 95% confidence interval [CI] -3.1 to 0.1) compared to less exercise; this was not statistically significant (p = 0.066). The association between exercise and headache days per month varied by baseline use of migraine prophylaxis (p-value of interaction = 0.009). Among those who reported regular use of migraine prophylaxis, a report of moderate-vigorous exercise at least three times per week was associated with 5.1 fewer headache days (-5.1: 95% CI -8.2 to -2.0; p = 0.001) compared to those who reported lower levels of exercise. However, among those not using migraine prophylaxis, we observed only 0.4 fewer headache days per month (-0.4: 95% CI -2.2 to 1.3; p = 0.636) associated with moderate-vigorous exercise at least three times/week, a result that was not statistically significant. There was no association of self-reported moderate-vigorous exercise at least three times a week with headache intensity or duration. CONCLUSION: In patients with EM, those who reported moderate-vigorous exercise at least three times per week had fewer headache days per month, though not statistically significant. This association was significantly stronger in those who used prophylactic medication for migraines. Exercise appeared not to be associated with the severity or duration of headaches. Routine moderate-vigorous exercise may be an important adjunctive strategy for improving headache burden in patients eligible for migraine prophylaxis.

Migraine-associated gene expression in cell types of the central and peripheral nervous system.

BACKGROUND: Genome-wide association studies have implicated dozens of genes with migraine susceptibility, but it remains unclear in which nervous system cell types these genes are expressed. METHODS: Using single-cell RNA sequencing data from the central and peripheral nervous system, including the trigeminal ganglion, the expression of putative migraine-associated genes was compared across neuronal, glial and neurovascular cell types within these tissues. RESULTS: Fifty-four putative migraine-associated genes were expressed in the central nervous system, peripheral nervous system or neurovascular cell types analyzed. Six genes (11.1%) were selectively enriched in central nervous system cell types, three (5.5%) in neurovascular cell types, and two (3.7%) in peripheral nervous system cell types. The remaining genes were expressed in multiple cell types. CONCLUSIONS: Single-cell RNA sequencing of the brain and peripheral nervous system localizes each migraine-associated gene to its respective nervous system tissue and the cell types in which it is expressed. While the majority of migraine-associated genes are broadly expressed, we identified several cell-type-specific migraine-associated genes in the central nervous system, peripheral nervous system, and neurovasculature. Trial registration: not applicable.

Sleep Disorders and Migraine: Review of Literature and Potential Pathophysiology Mechanisms.

Migraine shares a complex and poorly understood relationship with sleep. Patients consistently report poor sleep prior to migraine attacks and during them, identifying poor sleep as a migraine trigger. However, anecdotally, sleep is reported to serve a therapeutic role in terminating headache. Are the associations between migraine and sleep simply the result of various bidirectional relationships? A growing body of evidence suggests there may be a common underlying etiology as well. Our objective was to review studies of sleep and migraine from the last 2 decades utilizing validated subjective and objective measures of sleep and to explore potential mechanisms underlying this complex relationship by incorporating recent advances in neuroscience. We specifically focus on insomnia, obstructive sleep apnea, parasomnias, sleep related movement disorders, and REM sleep related disorders and their relationship to migraine. Parts of brainstem-cortical networks involved in sleep physiology are unintentionally being identified as important factors in the common migraine pathway. Recent discoveries on anatomic localization (the hypothalamus as a key and early mediator in the pathophysiology of migraine), common mediating signaling molecules (such as serotonin and dopamine), and the discovery of a new CNS waste removal system, the glymphatic system, all point to a common pathophysiology manifesting in migraine and sleep problems.

A Hospital Based Retrospective Study of Acute Postpartum Headache.

OBJECTIVE: To describe acute headache diagnoses in women presenting emergently in the postpartum period and to determine which factors may be associated with secondary vs primary headache. BACKGROUND: Hormonal, vascular, and procedural factors elevate the risk for both secondary and primary headache disorders in the postpartum period. Differentiating between these can be a diagnostic challenge, particularly among the most severe patients referred for urgent neurological consultation. METHODS: A single-center retrospective study of consecutive postpartum women age ≥18 years presenting with acute headache to a large urban tertiary-care hospital and receiving neurological consultation. RESULTS: Of 63 women who presented with acute postpartum headache, 17 (27.0%) were diagnosed with a primary headache disorder and 46 (73.0%) were diagnosed with a secondary headache disorder. Migraine comprised the majority of primary headache diagnoses (76.5%). Secondary headache most commonly featured postdural puncture headache (PDPH) (45.7%), postpartum preeclampsia (PEC) (26.1%), and a diverse group of cerebrovascular headache disorders (21.7%). Presentation within 24 hours and lack of side predominance helped to differentiate PDPH from migraine. However, abnormal diagnostic testing was more prevalent in the patients with headache secondary to cerebrovascular disorders/PEC. CONCLUSIONS: Nearly three-quarters of postpartum women who present with acute onset headache and receiving neurological consultation are found to have a secondary headache - with nearly half of the secondary headaches attributed to PEC or cerebrovascular headache disorders. The absence of a headache history and a clear PDPH description should prompt strong consideration for neuroimaging to rule out cerebrovascular etiologies of headache as well as close monitoring for signs and symptoms of preeclampsia in women presenting with acute severe postpartum headache.

Episodic Migraine With and Without Aura: Key Differences and Implications for Pathophysiology, Management, and Assessing Risks.

PURPOSE OF REVIEW: To review the pathophysiologic, epidemiologic, and clinical evidence for similarities and differences between migraine with and without aura. RECENT FINDINGS: The ICHD-3 has recently refined the diagnostic criteria for aura to include positive symptomatology, which better differentiates aura from TIA. Although substantial evidence supports cortical spreading depression as the cause of visual aura, the role (if any) of CSD in headache pain is not well understood. Recent imaging evidence suggests a possible hypothalamic origin for a headache attack, but further research is needed. Migraine with aura is associated with a modest increase in the risk of ischemic stroke. The etiology for this association remains unclear. There is a paucity of evidence regarding treatments specifically aimed at the migraine with aura subtype, or whether migraine with vs without aura responds to treatment differently. Migraine with typical aura is therefore often treated similarly to migraine without aura. Lamotrigine, daily aspirin, and flunarizine have evidence for efficacy in prevention of migraine with aura, and magnesium, ketamine, furosemide, and single-pulse transcranial magnetic stimulation have evidence for use as acute treatments. Although triptans have traditionally been contraindicated in hemiplegic migraine and migraine with brainstem aura, this prohibition is being reconsidered in the face of evidence suggesting that use may be safe. The debate as to whether migraine with and without aura are different entities is ongoing. In an era of sophisticated imaging, genetic advancement, and ongoing clinical trials, efforts to answer this question are likely to yield important and clinically meaningful results.

Headache and Facial Pain in Sickle Cell Disease.

Children and adolescents with sickle cell disease (SCD) have a high prevalence of recurrent headaches (24.0-43.9 %). Acute presentation with headache can be diagnostically challenging, as the clinician must consider evaluation of several potentially devastating conditions including vascular diseases (stroke, hemorrhage, venous sinus thrombosis, moyamoya, posterior reversible encephalopathy syndrome), facial and orbital bone infarcts, dental pain, and osteomyelitis. Patients with SCD and primary headache disorders may benefit from comprehensive headache treatment plans that include abortive therapy, prophylactic therapy, and non-pharmacological modalities. Although there is limited data in adults, those with SCD are at risk for medication overuse headache secondary to frequent opioid use. Addressing headache in patients with SCD may help to reduce their use of opioids and disability and improve pain and quality of life.

Insomnia symptoms, objective sleep duration and hypothalamic-pituitary-adrenal activity in children.

BACKGROUND: Insomnia symptoms are the most common parent-reported sleep complaints in children; however, little is known about the pathophysiology of childhood insomnia symptoms, including their association with hypothalamic-pituitary-adrenal (HPA) axis activation. The objective of this study is to examine the association between parent-reported insomnia symptoms, objective short sleep duration and cortisol levels in a population-based sample of school-aged children. DESIGN: A sample of 327 children from the Penn State Child Cohort (5-12 years old) underwent 9-h overnight polysomnography and provided evening and morning saliva samples to assay for cortisol. Objective short sleep duration was defined based on the median total sleep time (i.e., <7·7 h). Parent-reported insomnia symptoms of difficulty initiating and/or maintaining sleep were ascertained with the Pediatric Behavior Scale. RESULTS: Children with parent-reported insomnia symptoms and objective short sleep duration showed significantly increased evening (0·33±0·03 µg/dL) and morning (1·38±0·08 µg/dL) cortisol levels. In contrast, children with parent-reported insomnia symptoms and 'normal' sleep duration showed similar evening and morning cortisol levels (0·23±0·03 µg/dL and 1·13±0·08 µg/dL) compared with controls with 'normal' (0·28±0·02 µg/dL and 1·10±0·04 µg/dL) or short (0·28±0·02 µg/dL and 1·13±0·04 µg/dL) sleep duration. CONCLUSIONS: Our findings suggest that insomnia symptoms with short sleep duration in children may be related to 24-h basal or responsive physiological hyperarousal. Future studies should explore the association of insomnia symptoms with short sleep duration with physical and mental health morbidity.

The association between multidimensional sleep health and migraine burden among patients with episodic migraine.

STUDY OBJECTIVES: Using the Sleep Regularity, Satisfaction, Alertness, Timing, Satisfaction, and Duration (Ru-SATED) sleep health framework, we examined the association between multidimensional sleep health and headache burden in a cohort of 98 adults with episodic migraine. METHODS: Participants wore wrist actigraphs and completed twice-daily electronic diaries regarding sleep, headaches, and other health habits for 6 weeks. We calculated separate composite sleep health scores from diary and actigraphy assessed measures using the Ru-SATED framework. We used adjusted multivariable linear regression models to examine the association between composite sleep health scores and headache frequency, duration, and pain intensity. RESULTS: Among 98 participants (mean age: 35 ± 12 years; 87.8% female), 83 had healthy ranges in ≥ 3 sleep dimensions. In models adjusted for age, sex, menopausal status, physical activity and alcohol intake, good sleep health was associated with fewer headache days/month (actigraphy: 3.1 fewer days; 95% confidence interval: 0.9, 5.7; diary: 4.0 fewer days; 95% confidence interval: 1.1, 6.9). Results did not change substantively with further adjustment for stress and depressive symptoms. We did not observe an association between sleep health and headache duration or intensity, respectively. CONCLUSIONS: Among patients with episodic migraine, good multidimensional sleep health, but not the majority of singular dimensions of sleep, is associated with approximately 3-4 fewer headache days/month. In addition, there was no association with headache duration or intensity. These findings highlight the importance of assessing multiple dimensions of sleep and suggest that improving sleep health may be a potential clinical strategy to reduce headache frequency. CITATION: Yoo A, Vgontzas A, Chung J, et al. The association between multidimensional sleep health and migraine burden among patients with episodic migraine. J Clin Sleep Med. 2023;19(2):309-317.