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Objective: To describe acute and preventive treatment preferences among youth with migraine and their parents/guardians, and to describe the degree of youth-parent/guardian preference agreement., Background: Headache disorders are common in youth, but little is known about patient and family preferences for headache treatments and outcomes., Methods: In this cross-sectional survey, a headache treatment preferences questionnaire was co-created with stakeholders, piloted, and distributed to consenting youth with migraine aged 9-18 years and parents/guardians at a tertiary care headache clinic in western Canada. Response data were summarized for youth and parents/guardians separately, and agreement rates within a youth-parent/guardian pair were compared to a hypothesized agreement rate of 80% for the primary questionnaire items., Results: Seventy-two youth and n = 94 parents/guardians participated, with n = 63 in youth-parent/guardian pairs. Freedom from pain and rapid relief, and reducing pain severity and headache frequency were top acute and preventive treatment priorities, respectively. More than 90% (69/72) agreed that ≥ 50% reduction in headache frequency was a good target. For both acute and preventive interventions, swallowed pill-based options were most often selected as the preferred first-line treatment, with neuromodulation selected as the preferred second-line treatment. The level of agreement within youth-parent/guardian pairs on preferred treatment modalities was lower than hypothesized for acute (63% [40/63], 95% confidence interval [CI] = 52-75%, χ 2  = 10.73, p = 0.001) but not for preventive treatment (73% [46/63], 95% CI = 62-84%, χ 2  = 1.92, p = 0.166). Regarding which treatment modalities were perceived as most effective, youth-parent agreement was lower than hypothesized for both acute (48% [30/63], 95% CI = 35-60%, χ 2  = 41.29, p < 0.001) and preventive treatment (46% [29/63], 95% CI = 34-58%, χ 2  = 45.43, p < 0.001)., Conclusion: Youth and family preferences aligned qualitatively, but sometimes diverged quantitatively, from typical clinical trial outcomes. The level of agreement within youth-parent/guardian pairs on treatment preferences and perceptions was low. Clinicians should consider both perspectives as they may be divergent., (© 2024 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Objective: Temporomandibular disorders (TMD) may develop, especially among girls, during the adolescence period. The aim of this study was to study if information and advice in a school setting could prevent development of TMD symptoms and headaches during the early teenage period., Methods: Thirteen-year-old girls, at 19 upper elementary schools were invited to participate in a study with structured information about the jaw system, TMD symptoms and risk factors, as well as advice how to manage risk factor and TMD. Six hundred and fifty-one girls enrolled, of which 507 girls were followed for 2-2.5 years. Half received information on three occasions (cases), and the other half served as controls. Included in the analysis of incidence of TMD symptoms were those without frequently occurring TMD symptoms (not including headaches) at baseline (n = 396) and included in the analysis of incidence of headaches were those without frequent headaches at baseline (n = 297)., Result: The 2-year incidence of TMD symptoms was significantly lower in the information cohort (19%) compared to the controls (28%) (p = .03). The 2-year incidence of headaches was lower among those who were allocated to information (30%) compared to controls (40%), but the difference was not statistically significant (p = .099). Cases who had headaches at baseline reported a significantly lower prevalence at follow-up compared to controls (p = .03)., Conclusion: Standardized information in school settings can prevent development of TMD symptoms and headaches among young girls., (© 2024 The Author(s). Journal of Oral Rehabilitation published by John Wiley & Sons Ltd.)

Background and Objectives: In magnetic resonance-guided focused ultrasound (MRgFUS) procedures, headache is a frequent symptom and cause of treatment discontinuation. Herein, we assessed the efficacy of scalp nerve block (SNB) for alleviating headache during MRgFUS procedures., Methods: The effect of SNB on intraprocedural headache was examined by retrospectively comparing 2 patient cohorts at a single institution. During the study period from April 2020 to February 2022, an SNB protocol for all patients with a skull density ratio ≤0.55 was instituted on October 6, 2021. The number of patients with a skull density ratio ≤0.55 was 34 before the protocol and 36 afterward. Headache intensity was evaluated using a numerical rating scale (NRS) after each sonication. To evaluate the effect of SNB on headache intensity, multiple regression analysis was performed per patient and per sonication. In the per-patient analysis, the effect of SNB was evaluated using the maximum NRS, mean NRS, and NRS at the first ultrasound exposure that reached 52.5°C. In the per-sonication analysis, the effect of SNB was evaluated not only for the entire sonication but also for sonications classified into ≤9999 J, 10 000 to 29 999 J, and ≥30 000 J energy doses., Results: With SNB, headache alleviation was observed in the NRS after the first sonication that reached 52.5°C in each patient (β = -2.40, 95% CI -4.05 to -0.758, P = .00499), in the NRS when all sonications were evaluated (β = -0.647, 95% CI -1.19 to -0.106, P = .0201), and in the NRS when all sonications were classified into 10 000 to 29 999 J (β = -1.83, 95% CI -3.17 to -0.485, P = .00889)., Conclusion: SNB significantly reduced headache intensity during MRgFUS, especially that caused by sonication with a moderate-energy dose. These findings suggest that scalp nerves play a role in headache mechanisms during MRgFUS., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background and Purpose:

Face masks are crucial parts of personal protective equipment (PPE) to reduce the risk of respiratory infections. The COVID-19 outbreak has increased healthcare workers&rsquo; use of face masks. This study aimed to evaluate changes in cerebrovascular response among healthcare workers using surgical and N95 respirator masks.&nbsp;

90 healthcare workers: 30 wearing surgical masks, 30 wearing N95 respirators, and 30 without masks were included. After two-hour of face mask use, the baseline mean flow velocity (MFV) and the mean breath-holding index (BHI) of the bilateral middle cerebral arteries (MCAs) were evaluated with transcranial Doppler ultrasound. The presence of de-novo headache was recorded. BHI values ​​below 0.69 were evaluated as a sign of impaired cerebrovascular reactivity (CVR).&nbsp;

The rate of de-novo headache was significantly higher in the N95 respirator mask group (p = 0.004). Compared to the control and surgical mask groups, the N95 respirator mask group had significantly lower values of the baseline MFV of the right MCA (p = 0.003 and p = 0.021, respectively) and mean BHI (p = 0.003 and p = 0.012, respectively). Still, only one N95 respirator mask user had a mean BHI value below 0.69.

Surgical masks did not signi&shy;fi&shy;cantly affect cerebral hemodynamics. Although N95 respirator mask use significantly decreased BHI values, the CVR is still within normal limits, and the development of de-novo headache is not directly associated with low CVR.&nbsp;

Primary headaches can be prevented by medication, exercise, behavioral therapy, or lifestyle changes. It is important to note that if medication is used for prophylaxis, non-drug approaches should also be recommended as a complement. Patients often wish to address their headaches without medication. Except for cognitive behavioral therapy and biofeedback, the evidence for nonmedication approaches to headache management has not been definitively established. This article reviews the current literature on the evidence for endurance exercise, relaxation exercises, physical therapy, lifestyle factors, and complementary procedures. For tension-type headache, there is an increasing number of studies reporting positive results from physical therapy; long-term follow-up, however, are still pending. Aerobic endurance exercise has the best evidence as a measure for prevention of migraine. However, other methods can also be used., Competing Interests: Der Autor hat ein Vortragshonorar von der Firma Teva erhalten., (Thieme. All rights reserved.)

Background: Headache is a common occurrence after endoscopic endonasal surgery (EES) for pituitary adenomas and significantly impacts the quality of life of patients. This study aims to investigate the effectiveness of nasal irrigation in relieving postoperative headache after EES., Methods: A retrospective analysis was conducted on a cohort of 101 patients (Cohort I) who underwent EES for pituitary adenomas to explore the risk factors associated with postoperative headache. Another cohort of 72 patients (Cohort II) who received adjuvant nasal irrigation following surgery was enrolled for further analysis. The Headache Impact Test (HIT-6) was used to score the severity of headache, and patients with a HIT score > 55 were classified as having headache., Results: In Cohort I, 21.78% of patients experienced headache one month after EES, which decreased to 5.94% at the three-month follow-up. Multivariate analysis revealed that postoperative nasal sinusitis (OR = 3.88, 95%CI 1.16-13.03, p = 0.028) and Hardy's grade C-D (OR = 10.53, 95%CI 1.02-109.19, p = 0.049) independently predicted the presence of postoperative headache at one month. At the three-month follow-up, patients with sinusitis had higher HIT-6 scores compared to those without sinusitis (44.43 ± 9.78 vs. 39.72 ± 5.25, p = 0.017). In Cohort II, the incidence of sinusitis at three months was significantly lower than that in Cohort I (p = 0.028). Importantly, both the incidence of headache and HIT-6 scores in Cohort II were significantly lower than those in Cohort I at the one- and three-month follow-ups., Conclusions: Postoperative sinusitis is an independent risk factor for the development of headache following EES for pituitary adenomas. Prophylactic nasal irrigation helps relieve postoperative headache, possibly by preventing the occurrence of sinusitis., (© 2024. The Author(s).)

Background: Nitroglycerin (NTG)-induced headache is the most common side effect of nitrate therapy and negatively affects the quality of life., Aims: To assess the preventive and severity-reducing effect of cold compresses applied to the bilateral frontotemporal and occipital regions, where pain is most frequently experienced, for headache among individuals receiving intravenous NTG treatment., Study Design: This research used an observational, two-group, pretest-posttest design and was completed from October 2020 to May 2021 in the coronary intensive care unit of a state hospital located in the north of Turkey. The first group in the research had cold compresses applied for 20 min with the aid of an applicator at the start of NTG infusion, while the second group had the same implementation when headache developed during infusion., Results: Both groups were similar in terms of the demographic and clinical features of participants. In our study, more headache was observed in the group without local cold compresses at the start of infusion (53.3%) compared with the group with local cold compresses at the start of infusion (25.8%) (χ 2  = 4.841, p = .028). In both groups, the heart rate, systolic and diastolic blood pressure values of patients significantly approached normal values after cold compresses. Patients with local cold compresses applied when headache developed had significantly different visual analog scale scores before (5.75) and after (2.00) the cold compresses application (z = 3.558, p = .000)., Conclusion: At the beginning of the infusion, local cold compresses application may prevent NTG-induced headache in patients without headache, and local cold compresses applied when headache develops may reduce the severity of NTG-induced headache., Relevance to Clinical Practice: Application of cold compresses immediately when treatment begins is recommended as a simple and effective practice with no side effects for patients receiving NTG treatment., (© 2022 British Association of Critical Care Nurses.)

Headaches in children and adolescents are an actual problem of modern medicine. In most cases, headaches are regarded as a manifestation of vertebrogenic or cerebrovascular pathology, or as a manifestation of autonomic dystonia syndrome which leads to an erroneous diagnosis and treatment. The review considers the factors of occurrence and chronicity of primary headaches (hypodynamia, postural disorders, magnesium and vitamin D deficiency, anxiety and depression, central sensitization, alexithymia), methods for their diagnosis and treatment.

Competing Interests: Conflicts of interest The authors declare no conflicts of interest.

Background: Fremanezumab has demonstrated to be effective, safe, and tolerated in the prevention of episodic or chronic migraine (CM) in randomized, placebo-controlled trials (RCTs). Real-life studies are needed to explore drug effects in unselected patients in routine circumstances and to provide higher generalizability results. This study explores the effectiveness, safety, and tolerability of fremanezumab in a real-life population of individuals affected by high-frequency episodic (HFEM: 8-14 days/month) or CM., Methods: This is a 12-week multicenter, prospective, cohort, real-life study. We considered all consecutive patients affected by HFEM or CM visited at 9 Italian headache centers from 28/07/2020 to 11/11/2020. Eligible patients were given subcutaneous fremanezumab at the doses of 225 mg monthly or 675 mg quarterly, according to their preference. Primary study endpoints were the change in monthly migraine days (MMDs) in HFEM and monthly headache days (MHDs) in CM patients at weeks 9-12 compared to baseline. Secondary endpoints encompassed variation in monthly analgesic intake (MAI), Numerical Rating Scale (NRS), HIT-6 and MIDAS scores, and ≥ 50%, ≥ 75% and 100% responder rates at the same time intervals., Results: Sixty-seventh number migraine patients had received ≥ 1 subcutaneous fremanezumab dose and were considered for safety analysis, while 53 patients completed 12 weeks of treatment and were included also in the effectiveness analysis. Fremanezumab was effective in both HFEM and CM, inducing at week 12 a significant reduction in MMDs (-4.6, p < 0.05), MHDs (-9.4, p < 0.001), MAI (-5.7, p < 0.05; -11.1, p < 0.001), NRS (-3.1, p < 0.001; -2.5, p < 0.001), and MIDAS scores (-58.3, p < 0.05; -43.7; p < 0.001). HIT-6 was significantly reduced only in HFEM patients (-18.1, p < 0.001). Remission from CM to episodic migraine and from MO to no-MO occurred in 75% and 67.7% of the patients. The ≥ 50%, ≥ 75% and 100% responder rates at week 12 were 76.5%, 29.4% and 9.9% in HFEM and 58.3%, 25% and 0% in CM. Younger age emerged as a positive response predictor (OR = 0.91; 95% CI 0.85-0.98, p = 0.013). Treatment-emergent adverse events were uncommon (5.7%) and mild. No patient discontinued fremanezumab for any reason., Conclusions: Fremanezumab seems more effective in real-life than in RCTs. Younger age emerges as a potential response predictor., (© 2022. The Author(s).)

Introduction : Existing oral prophylaxis for chronic migraine (CM) are often ineffective or poorly tolerated. OnabotulinumtoxinA (onabotA) is approved for headache prophylaxis in CM and ameliorates headaches in patients refractory to multiple preventatives. Areas covered : We appraise evidence regarding action mechanisms, pharmacodynamics, and pharmacokinetics of onabotA in CM prophylaxis. We critically evaluate salient clinical and real-world studies demonstrating its efficacy in improving multiple aspects of CM. We discuss onabotA safety, tolerability, and adverse events (AEs) for CM prophylaxis from clinical trials, post-authorization studies and meta-analyses, including novel pregnancy safety data and comparisons with oral prophylactics. We explore areas of future interest, particularly onabotA safety and efficacy in the context of novel antibody-based prophylaxis. Expert opinion : Clinical and real-world evidence demonstrate onabotA safety, tolerability and efficacy for CM prophylaxis. Most AEs are mild/moderate and self-limiting, with few serious AEs and no treatment-related deaths. Common AEs include neck pain, ptosis, muscle weakness, and stiffness. Modifying existing responder-criteria enables more patients to benefit from onabotA. OnabotA shows superior safety and efficacy to oral preventatives, and appears safe in pregnancy. Future pregnancy-risk register will clarify pregnancy and lactation safety further. Future research comparing onabotA safety and efficacy with newly emergent antibody-based prophylaxis is keenly awaited.

Importance: Migraine is a common neurological disease that often begins in childhood and continues into adulthood; approximately 6 million children and adolescents in the United States cope with migraine, and many frequently experience significant disability and multiple headache days per week. Although pharmacological preventive treatments have been shown to offer some benefit to youth with migraine, additional research is needed to understand whether and how these benefits are sustained., Objective: To survey clinical status of youth with migraine who participated in the 24-week Childhood and Adolescent Migraine Prevention (CHAMP) trial over a 3-year follow-up period., Design, Setting, and Participants: This survey study used internet-based surveys collected from youth ages 8 to 17 years at 3, 6, 12, 18, 24, and 36 months after completion of the CHAMP trial, which randomized participants to amitriptyline, topiramate, or placebo. At the end of the trial, the study drug was stopped, and participants received clinical care of their choice thereafter. The CHAMP trial was conducted between May 2012 and November 2015, and survey follow-up was conducted June 2013 to June 2018. Participants in this survey study were representative of those randomized in the trial. Data were analyzed from March 2020 to April 2021., Exposures: Survey completion., Main Outcomes and Measures: Headache days, disability (assessed using the Pediatric Migraine Disability Scale [PedMIDAS]), and self-report of ongoing use of prescription preventive medication., Results: A total of 205 youth (mean [SD] age, 14.2 [2.3] years; 139 [68%] girls; mean [SD] history of migraine, 5.7 [3.1] years) participated in the survey. Retention of participants was 189 participants (92%) at month 6, 182 participants (88%) at month 12, 163 participants (80%) at month 18, 165 participants (80%) at month 24, and 155 participants (76%) at month 36. Over the course of the 3-year follow-up, participants consistently maintained meaningful reductions in headache days (mean [SD] headache days per 28 days: CHAMP baseline, 11.1 [6.0] days; CHAMP completion, 5.0 [5.7] days; 3-year follow-up, 6.1 [6.1] days) and disability (mean [SD] score: CHAMP baseline, 40.9 [26.4]; CHAMP completion, 17.9 [22.1]; 3-year follow-up, 12.3 [20.0]). At 3 years after completion of the CHAMP trial, headache days were approximately 1.5 per week (changed from about 3 per week at trial baseline) and disability had improved from the moderate range to the low mild range on the PedMIDAS. Longitudinal analyses showed that amitriptyline and topiramate did not explain intercept random effects for either mean rate of headache days per week (amitriptyline: estimate [SE], 0.07 [0.05]; P = .16; topiramate: estimate [SE], 0.04 [0.05]; P = .50) or headache disability PedMIDAS total score (amitriptyline: estimate [SE], 0.25 [0.38]; P = .52; topiramate: estimate [SE], -0.09 [0.39]; P = .82) changes over time. Of 153 participants who reported on prescription drug use at 3 years, only 1 participant (1%) reported using prevention medication, and most participants reported no medication use at most time points., Conclusions and Relevance: These findings suggest that children and adolescents with longer than 5 years history of migraine who participated in the CHAMP trial may sustain positive clinical outcomes over time, even after discontinuing preventive pill-based treatment. This survey study could inform use and discontinuation timing of pharmacological preventive therapies for migraine in youth ages 8 to 17 years. Research is needed to examine mechanisms of treatment improvement and maintenance for preventive therapies, as well as placebo, in the pediatric population.

Background: The purpose of this study was to clarify the practical clinical treatment for acute carbon monoxide (CO) poisoning in Japan and to investigate the efficacy of hyperbaric oxygen (HBO2) therapy in preventing delayed neurological sequelae (DNS) in the acute phase of CO poisoning., Methods: We conducted a multicenter, prospective, observational study of acute CO poisoning in Japan. Patients with acute CO poisoning were enrolled and their treatment details were recorded. The primary endpoint was the onset of DNS within 2 months of CO exposure. Factors associated with DNS were assessed with logistic regression analysis., Results: A total of 311 patients from 57 institutions were registered and 255 were analyzed: 171 received HBO2 therapy (HBO2 group) and 84 did not (normobaric oxygen [NBO2] group). HBO2 therapy was performed zero, once, twice, or three times within the first 24 h in 1.8%, 55.9%, 30.9%, and 11.3% of the HBO2 group, respectively. The treatment pressure in the first HBO2 session was 2.8 ATA (47.9% of the HBO2 group), 2.0 ATA (41.8%), 2.5 ATA (7.9%), or another pressure (2.4%). The incidence of DNS was 13/171 (7.6%) in the HBO2 group and 3/84 (3.6%) in the NBO2 group (P = 0.212). The number of HBO2 sessions in the first 24 h was one of the factors associated with the incidence of DNS (odds ratio, 2.082; 95% confidence interval, 1.101-3.937; P = 0.024)., Conclusions: The practical clinical treatment for acute CO poisoning, including HBO2 therapy, varied among the institutions participating in Japan. HBO2 therapy with inconsistent protocols showed no advantage over NBO2 therapy in preventing DNS. Multiple HBO2 sessions was associated with the incidence of DNS., Competing Interests: The authors have declared that no competing interests exist.

Objective: To evaluate the impact of fremanezumab on the severity and duration of remaining migraine attacks in patients with chronic migraine (CM) or episodic migraine (EM)., Background: Fremanezumab is a fully humanized monoclonal antibody (IgGΔa) that selectively targets calcitonin gene-related peptide and is efficacious in reducing migraine frequency., Methods: This exploratory post hoc analysis included data from three randomized, double-blind, 12-week, phase 3 studies (HALO CM, HALO EM, and FOCUS). In all three studies, patients with CM or EM were randomized 1:1:1 to receive subcutaneous quarterly fremanezumab (month 1/2/3: 675 mg/placebo/placebo), monthly fremanezumab (month 1/2/3: 675 mg [CM], 225 mg [EM]/225 mg/225 mg), or matched monthly placebo. Changes from baseline were evaluated in the proportion of headache days of at least moderate severity, peak severity of headache days, mean monthly headache hours (of any severity and at least moderate severity), and mean headache hours per headache day of any severity., Results: A total of 2843 patients were randomized with 2823 patients included in the efficacy analyses across all studies (HALO CM, N = 1121; HALO EM, N = 865; FOCUS, N = 837). At study baseline, mean (standard deviation [SD]) monthly number of headache days rated moderate or severe in the quarterly fremanezumab, monthly fremanezumab, and placebo groups, respectively, were 13.2 (5.5), 12.8 (5.8), and 13.3 (5.8) in HALO CM; 7.2 (3.1), 6.8 (2.9), and 6.9 (3.1) in HALO EM; and 12.4 (5.8), 12.7 (5.8), and 12.8 (5.9) in FOCUS. Patients experienced significant least-squares mean (LSM; 95% confidence interval) percent reductions from baseline in monthly number of headache days rated moderate or severe during the 12 weeks: HALO CM, quarterly fremanezumab, 34.5% (-39.8, -29.2) and monthly fremanezumab, 36.2% (-41.4, -31.0) vs. placebo, 19.6% (-20.0, -14.3); HALO EM, quarterly fremanezumab, 40.7% (-47.8, -33.5) and monthly fremanezumab, 43.4% (-50.4, -36.3) vs. placebo, 17.9% (-24.9, -11.0); and FOCUS, quarterly fremanezumab, 36.5% (-41.9, -31.1) and monthly fremanezumab, 38.6% (-44.0, -33.3) vs. placebo, 3.5% (-8.9, 1.8); all p < 0.0001. At study baseline, mean (SD) number of monthly headache hours rated moderate or severe in the quarterly fremanezumab, monthly fremanezumab, and placebo groups, respectively, were 66.4 (58.8), 68.0 (53.9), and 68.5 (57.0) in HALO CM; 33.3 (25.4), 31.7 (23.7), and 31.6 (23.2) in HALO EM; and 59.2 (54.7), 64.3 (65.2), and 65.9 (70.2) in FOCUS. Significant reductions were observed in LSM (standard error) number of monthly headache hours of at least moderate severity: HALO CM, quarterly fremanezumab, 24.4 (2.5) and monthly fremanezumab, 26.4 (2.3) vs. placebo, 14.1 (2.5); HALO EM, quarterly fremanezumab, 14.5 (1.4) and monthly fremanezumab, 15.5 (1.3) vs. placebo, 8.1 (1.3); and FOCUS, quarterly fremanezumab, 16.8 (3.0) and monthly fremanezumab, 18.3 (3.0) vs. placebo, 2.3 (3.0); all p < 0.001., Conclusion: These analyses demonstrated that quarterly or monthly treatment with fremanezumab significantly reduced headache severity and duration in patients with CM or EM, including in patients with documented inadequate response to two to four prior migraine preventive medication classes., (© 2021 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Background: Caffeine is the most utilised psychoactive drug worldwide. However, caffeine withdrawal and the therapeutic use of caffeine in intensive care and in the perioperative period have not been well summarised. Our objective was to conduct a scoping review of caffeine withdrawal and use in the intensive care unit (ICU) and postoperative patients., Methods: PubMed, Embase, CINAHL Complete, Scopus and Web of Science were systematically searched for studies investigating the effects of caffeine withdrawal or administration in ICU patients and in the perioperative period. Areas of recent systematic review such as pain or post-dural puncture headache were not included in this review. Studies were limited to adults., Results: Of 2268 articles screened, 26 were included and grouped into two themes of caffeine use in in the perioperative period and in the ICU. Caffeine withdrawal in the postoperative period increases the incidence of headache, which can be effectively treated prophylactically with perioperative caffeine. There were no studies investigating caffeine withdrawal or effect on sleep wake cycles, daytime somnolence, or delirium in the intensive care setting. Administration of caffeine results in faster emergence from sedation and anaesthesia, particularly in individuals who are at high risk of post-extubation complications. There has only been one study investigating caffeine administration to facilitate post-anaesthetic emergence in ICU. Caffeine administration appears to be safe in moderate doses in the perioperative period and in the intensive care setting., Conclusions: Although caffeine is widely used, there is a paucity of studies investigating withdrawal or therapeutic effects in patients admitted to ICU and further novel studies are a priority.

We present a series of general and specific recommendations based on pathophysiologic considerations for managing the most common adverse effects of apremilast that lead to treatment discontinuation: diarrhea, nausea, and headache. The recommendations are based on a review of the literature and the experience of a multidisciplinary team of 14 experts including dermatologists, rheumatologists, neurologists, gastroenterologists, pharmacists, and nurses. We propose a series of simple algorithms that include clinical actions and suggestions for pharmacologic treatment. The adverse effects of apremilast can be managed from a multidisciplinary approach. The purpose of optimizing management is to bring clinical benefits to patients., (Copyright © 2020 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: In recent months, doubts have arisen among patients, general practitioners, and neurologists as to whether some drugs commonly used in patients with headaches and neuralgia may favour or complicate the disease caused by SARS-CoV-2., Material and Methods: We collected information on the opinions of scientific societies and medicines agencies (American, European, and Spanish) to clarify doubts regarding the use of drugs such as lisinopril, candesartan, ibuprofen, corticosteroids, carbamazepine, and monoclonal antibodies targeting the calcitonin gene-related peptide in the context of the COVID-19 pandemic., Results: We make recommendations about the use of standard headache treatments in the context of the COVID-19 pandemic, based on the current scientific evidence., Conclusions: At present, there is no robust scientific argument to formally contraindicate any of the standard treatments employed for headaches and neuralgias., (Copyright © 2020 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: The use of cytostatic drugs such as Mitomycin C and 5-Fluorouracil is well-known in glaucoma filtering surgery, as well as the management of its complications. However, there is a lack of information regarding the preventive measures to be taken by the professional that handles these types of substances., Objective: Raise awareness among professionals of the risks associated with the use of cytostatic drugs without adequate prevention measures., Results: Review of the available literature and legislation on preventive measures in the management of cytostatic drugs in the medical and ophthalmological field., Conclusions: The prevention and awareness of the risks of the qualified professionals that handle these substances is the most important measure to prevent the possible risks. Coordination is necessary with the Occupational Health teams of the Hospital, as well as the professionals and staff involved in the different phases of the process, from the preparation in Hospital Pharmacy to its elimination., (Copyright © 2020 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Idiopathic intracranial hypertension (IIH) is a condition associated with poor vision and headaches that can cause disability and reduced quality of life. The onset of IIH is typically associated with sudden weight gain and obesity, which may be due to first-generation or second-generation antipsychotics. This case involved the use of quetiapine in an obese, 28-year-old woman; she gained significant weight after starting the antipsychotic and later developed headaches and blurred vision. Reducing quetiapine and administering acetazolamide significantly improved her symptoms within 4 weeks. This case reminds physicians to consider IIH as a cause of headache and vision loss in patients who have gained weight after starting or increasing quetiapine., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

INTRODUCTION: Airplane headache (AH) is unique to plane travel and looks like a short duration migraine attack or paroxysmal hemicrania (PH) attack without any autonomic symptoms. Until now, there has been no documented association between AH and PH. CASE REPORT: We report a 50-yr-old healthy woman with a very severe and sudden pulsating headache located in the left frontal region with radiation into the left eye during takeoff which diminished within 10-15 min during her airplane journeys. DISCUSSION: The patient was diagnosed with AH and she had good response to indomethacin. The pain was unique to plane travel but looked like PH. We discuss the association between AH and PH attack in the light of diagnostic criteria and therapeutic approach in the report. Koçer A. Headache attack similar to paroxysmal hemicrania seen during flight. Aerosp Med Hum Perform. 2020; 91(4):373-375.

Introduction: High altitude headache (HAH) and acute mountain sickness (AMS) are common pathologies at high altitudes. There are similarities between AMS and migraine headaches, with nausea being a common symptom. Several studies have shown ibuprofen can be effective for AMS prophylaxis, but few have addressed treatment. Metoclopramide is commonly administered for migraine headaches but has not been evaluated for HAH or AMS. We aimed to evaluate metoclopramide and ibuprofen for treatment of HAH and AMS., Methods: We performed a prospective, double-blinded, randomized, field-based clinical trial of metoclopramide and ibuprofen for the treatment of HAH and AMS in 47 adult subjects in the Mount Everest region of Nepal. Subjects received either 400 mg ibuprofen or 10 mg metoclopramide in a 1-time dose. Lake Louise Score (LLS) and visual analog scale of symptoms were measured before and at 30, 60, and 120 min after treatment., Results: Subjects in both the metoclopramide and ibuprofen arms reported reduced headache severity and nausea compared to pretreatment values at 120 min. The ibuprofen group reported 22 mm reduction in headache and 6 mm reduction in nausea on a 100 mm visual analog scale at 120 min. The metoclopramide group reported 23 mm reduction in headache and 14 mm reduction in nausea. The ibuprofen group reported an average 3.5-point decrease on LLS, whereas the metoclopramide group reported an average 2.0-point decrease on LLS at 120 min., Conclusions: Metoclopramide and ibuprofen may be effective alternative treatment options in HAH and AMS, especially for those patients who additionally report nausea., (Copyright © 2019 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

This article describes a man who presented with a 2-week history of atraumatic, unilateral, retro-orbital cranio-facial pain, ipsilateral diaphoresis, and facial flushing. He was diagnosed with cluster headaches after a positive response to oxygen therapy. Early consideration for oxygen therapy in the acute setting should be considered in all patients with an acute, unilateral, retro-orbital headache.

Some studies have suggested a link between vitamin D and headache; however, the underlying physiological mechanisms are unclear. We aimed to summarize the available evidence on the relationship between vitamin D and the various subtypes of primary headaches, including migraines and tension-type headaches. All articles concerning the association between primary headache and vitamin D published up to October 2019 were retrieved by searching clinical databases, including: EMBASE, MEDLINE, PubMed, Google scholar, and the Cochrane library. All types of studies (i.e., observational, cross-sectional, case-control, and clinical trials) were included. We identified 22 studies investigating serum vitamin D levels in association with headaches. Eight studies also evaluated the effect of vitamin D supplementation on the various headache parameters. Among them, 18 studies showed a link between serum vitamin D levels and headaches, with the strongest connection reported between serum vitamin D levels and migraine. Overall, there is not enough evidence to recommend vitamin D supplementation to all headache patients, but the current literature indicates that it may be beneficial in some patients suffering headaches, mainly migraineurs, to reduce the frequency of headaches, especially in those with vitamin D deficiency.

Aim: To study the compliance of neurologists and headache specialists to chronic headache and chronic migraine (CM) diagnosis and treatment guidelines., Material and Methods: The survey included 634 neurologists from all regions of the Russian Federation. Mean age of respondents was 40.7±8.5 years, mean years of experience 14.2±7.8 years., Results: Most doctors work in outpatient or hospital settings (49% and 24%, respectively), 7% were headache specialists. Tension-type headache (TTH) was diagnosed in 30% and CM in 17% of patients while 44% of patients were presumed to have a mixed headache disorder (TTH+CM). Only 10% of physicians do not use instrumental diagnostic methods in chronic headache. This study has shown sufficient attention to comorbid conditions and frequent prescription of headache preventative treatment. Botox prescription data is equivocal: 35% of physicians recommend such treatment, 27% do not, while other doctors prescribe it for off-label indications., Conclusion: To overcome clinical inertia, further education in chronic headaches and their optimal treatment is warranted.

Methods: Prolactin (PRL) secreting adenomas are associated with high incidence of headache. The role of hyperprolactinemia in the headache context is not clear, nor is the effect of its treatment on headache. The present longitudinal study evaluated hyperprolactinemic patients (69), in terms of presence and characteristics of headache before and after hyperprolactinemia treatment., Results: Headache was reported by 45 (65.2%) patients, independent of the etiology of hyperprolactinemia. The migraine phenotype was the most prevalent (66.6%). Medications used in the treatment of headache not changed during the study. The first line of treatment of hyperprolactinemia was dopaminergic agonists. In the last reevaluation, PRL level under treatment was within the reference range in 54.7% of the cases, and it was observed complete or partial resolution of the headache in 75% of the cases. The median PRL at this time in patients with complete headache resolution was 17 ng/mL, in those who reported partial recovery was 21 ng/mL, and in those in whom the headache did not change was 66 ng/mL, with a significant difference between the group with complete headache resolution vs. the group with unchanged headache (p=0.022). In the cases with complete headache resolution, the median fall on PRL levels was 89% and in those cases with partial headache resolution 86%, both significantly different (p<0.001) from the fall in the cases with an unchanged headache., Conclusion: Data allow us to conclude that, in this series, in the majority of cases the reduction in the level of PRL was followe3d by cessation or relief of the pain.

Background: Vestibular migraine (VM) is the most frequent cause of recurrent spontaneous attacks of vertigo causally related to migraine. The objective of the Prophylactic treatment of vestibular migraine with metoprolol (PROVEMIG) trial was to demonstrate that metoprolol succinate is superior to placebo in the prevention of episodic vertigo- and migraine-related symptoms in patients with VM., Methods: This phase III, two-arm, parallel-group, double-blind, randomized placebo-controlled trial was designed to be conducted at tertiary referral centres at neurology and ear, nose and throat departments of eight German university hospitals. The planned sample size was a total of 266 patients to be allocated. Adults aged 18 years or above diagnosed with probable or definitive VM according to the Neuhauser criteria 2001 were randomly assigned 1:1 to 6 months blinded metoprolol (maintenance dosage of 95 mg daily) or placebo. The primary efficacy outcome was the self-reported number of vertiginous attacks per 30 days documented by means of a paper-based daily symptom diary. The pre-specified time period of primary interest was defined as months 4 to 6. Secondary outcomes included the patient-reported number of migraine days and vertigo days, the Dizziness Handicap Inventory, and clinical assessments. Adverse events were reported throughout the whole 9-month study period., Results: At the time of trial termination, no evidence for a difference in the incidence of vertiginous attacks between groups was detected. For the full analysis set, the incidence rate ratio was 0.983 (95% confidence interval (CI) 0.902-1.071) for metoprolol versus placebo. In both groups, there was a significant decline over time in the overall monthly vertigo attacks by a factor of 0.830 (95% CI 0.776-0.887). Results were consistent for all subjective and objective key measures of efficacy. The treatment was well tolerated with no unexpected safety findings., Conclusions: After randomizing 130 patients PROVEMIG had to be discontinued because of poor participant accrual not related to the tolerability of the study medication or safety concerns; no treatment benefit of metoprolol over placebo could be established. Additional preparatory work is much needed in the development, psychometric evaluation and interpretation of clinically meaningful end points in trials on episodic syndromes like VM taking into consideration the complexity of this disease entity comprising two domains (vertigo- and headache-related disability)., Trial Registration: EudraCT, 2009-013701-34. Prospectively registered on 8 April 2011.

Aims: To evaluate the crossover design in migraine preventive treatment trials by assessing dropout rate, and potential period and carryover effect in four placebo-controlled randomized controlled trials (RCTs)., Methods: In order to increase statistical power, the study combined data from four different RCTs performed from 1998 to 2015 at St. Olavs Hospital, Norway. Among 264 randomized patients, 120 received placebo treatment before and 144 after active treatment., Results: Only 26 (10%) dropped out during the follow-up period of 30-48 weeks, the majority (n = 19) in the first 12 weeks. No period effect was found, since the treatment sequence did not influence the responder rate after placebo treatment, being respectively for migraine 30.5% vs. 27.4% (p = 0.59) and for headache 25.0% vs. 24.8% (p = 0.97, Chi-square test) when placebo occurred early or late. Furthermore, no carryover effect was identified, since the treatment sequence did not influence the treatment effect (difference between placebo and active treatment). There was no significant difference between those who received active treatment first and those who received placebo first with respect to change in number of days per 4 week of headache (- 0.9 vs. -1.3, p = 0.46) and migraine (- 1.2 vs. -0.9, p = 0.35, Student's t-test)., Conclusions: Summary data from four crossover trials evaluating preventive treatment in adult migraine showed that few dropped out after the first period. No period or carryover effect was found. RCT studies with crossover design can be recommended as an efficient and cost-saving way to evaluate potential new preventive medicines for migraine in adults.

Background: The aim of this study is to determine the efficacy of preemptive analgesia with paracetamol and ibuprofen to reduce the intensity and incidence of headache and myalgia after electroconvulsive therapy (ECT)., Methods: Sixty patients with major depression who were treated with ECT were randomized to receive ECT 3 times a week. The first 3 sessions were included in the study. The patients were divided into 3 groups; Group C (Control, Saline, n = 20), Group P (Paracetamol, n = 20), and Group I (Ibuprofen, n = 20). Demographics, duration of seizure, visual analog scale (VAS) for headache and myalgia and nausea, vomiting and pruritus were evaluated at postoperative 24 hours period., Results: Duration of seizure after ECT was similar in all groups (P = .148). In the study, heart rate and mean arterial pressure were found to be some changes in some of the sessions. There were no significant differences in any comparison for all groups in all sessions regarding VAS scores for headache and myalgia. Incidence of headache and myalgia in Group I was lower than the other groups (P = .233, P = .011, respectively). But, there was no significant difference between the other groups. There was no significant difference in vomiting, intergroups, and intragroup., Conclusions: The findings of our study indicate that pain intensity of headache and myalgia did not show a significant change between groups and within groups. While pain intensity of myalgia between the groups reached no statistical significance, ibuprofen was significantly lowered the incidence of myalgia at postoperative 24 hours period.

Objective: To compare effectiveness of onabotulinumtoxinA and topiramate for chronic migraine (CM) prevention., Background: The efficacy* of onabotulinumtoxinA and topiramate has been established in placebo-controlled randomized clinical trials (*defined as the benefit of treatment under ideal conditions). The effectiveness* of the 2 preventive treatments, however, has not been established (*the benefit of treatment under real-world conditions, representing a blend of efficacy and tolerability)., Methods: In this multicenter, randomized, parallel-group, post-authorization, open-label prospective study (FORWARD; ClinicalTrials.gov, NCT02191579), we randomized adults with CM (1:1) to onabotulinumtoxinA 155 U every 12 weeks for 3 cycles or topiramate "immediate release" 50-100 mg/day to week 36. Primary outcome measure was proportion of patients achieving ≥50% reduction in headache days (weeks 29-32). Missing values were imputed using baseline observation carried forward (BOCF) methodology. After 12 weeks, patients initially randomized to topiramate could cross over to onabotulinumtoxinA treatment. We monitored and recorded all adverse events (AEs)., Results: We enrolled 282 patients (onabotulinumtoxinA, n = 140; topiramate, n = 142) and 148 patients completed randomized treatment (onabotulinumtoxinA, n = 120 [86%]; topiramate, n = 28 [20%]). Primary reasons for withdrawal were ineffective treatment (onabotulinumtoxinA, n = 7 [5%]; topiramate, n = 27 [19%]) and AEs (onabotulinumtoxinA, n = 5 [4%]; topiramate, n = 72 [51%]). Eighty topiramate patients crossed over to onabotulinumtoxinA. In the BOCF analysis, a significantly higher proportion of patients randomized to onabotulinumtoxinA experienced ≥50% reduction in headache frequency compared with those randomized to topiramate (40% [56/140] vs 12% [17/142], respectively; adjusted OR, 4.9 [95% CI, 2.7-9.1]; P < .001). OnabotulinumtoxinA was superior to topiramate in meeting secondary endpoints. In a post hoc analysis using observed data, the 50% responder rates at week 12 were 45.6% for onabotulinumtoxinA (n = 125) and 29.4% for topiramate (n = 109) (P = .015). AEs were reported by 48% (105/220) of onabotulinumtoxinA and 79% (112/142) of topiramate patients. Results were similar in those who crossed over to onabotulinumtoxinA., Conclusions: While using imputation methods of accounting for differences in discontinuation rates, we found onabotulinumtoxinA to have greater clinical utility than topiramate, largely because of tolerability issues associated with the latter and a relatively higher number of onabotulinumtoxinA patients remaining on treatment., (© 2019 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals, Inc. on behalf of American Headache Society.)

Medication-overuse headache is defined as headache occurring on more than 15days in a month in people with pre-existing primary headache, and developing as a consequence of regular overuse of acute headache treatments. Medication-overuse headache is common in general neurology clinics and can be difficult to manage. Most patients have a background of migraine, which has slowly transformed over months and years from the episodic to chronic form; with this comes an increased use of acute migraine treatment. This paper identifies who is at risk of developing medication-overuse headache, and reviews preventive measures and current treatment strategies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To provide updated evidence-based recommendations for migraine prevention using pharmacologic treatment with or without cognitive behavioral therapy in the pediatric population., Methods: The authors systematically reviewed literature from January 2003 to August 2017 and developed practice recommendations using the American Academy of Neurology 2011 process, as amended., Results: Fifteen Class I-III studies on migraine prevention in children and adolescents met inclusion criteria. There is insufficient evidence to determine if children and adolescents receiving divalproex, onabotulinumtoxinA, amitriptyline, nimodipine, or flunarizine are more or less likely than those receiving placebo to have a reduction in headache frequency. Children with migraine receiving propranolol are possibly more likely than those receiving placebo to have an at least 50% reduction in headache frequency. Children and adolescents receiving topiramate and cinnarizine are probably more likely than those receiving placebo to have a decrease in headache frequency. Children with migraine receiving amitriptyline plus cognitive behavioral therapy are more likely than those receiving amitriptyline plus headache education to have a reduction in headache frequency., Recommendations: The majority of randomized controlled trials studying the efficacy of preventive medications for pediatric migraine fail to demonstrate superiority to placebo. Recommendations for the prevention of migraine in children include counseling on lifestyle and behavioral factors that influence headache frequency and assessment and management of comorbid disorders associated with headache persistence. Clinicians should engage in shared decision-making with patients and caregivers regarding the use of preventive treatments for migraine, including discussion of the limitations in the evidence to support pharmacologic treatments., (© 2019 American Academy of Neurology.)

Chronic Migraine (CM) is a disabling neurologic condition with a severe impact on functioning and quality of life. Successful therapeutic management of patients with CM is complex, and differences in therapeutic response could be attributable to genetically determined factors, sensitivity to pharmacological treatment, psychosocial and relational factors affecting the patient's compliance and approach on the therapeutic treatment. The aim of this prospective observational study was to explore self-efficacy, coping strategies, psychological distress and headache-related disability in a cohort of 40 patients with CM (mean age: 46.73; standard deviation 13.75) treated with OnabotulinumtoxinA and the relationship between these clinical and psychological aspects and acute medication consumption during OnabotulinumtoxinA prophylactic treatment. Patients presented an overall significant reduction in the Headache Index (HI) ( p < 0.001), HI with severe intensity ( p = 0.009), and total analgesic consumption ( p = 0.003) after the prophylactic treatment. These results are in line with the literature. Despite this, higher nonsteroidal anti-inflammatory drugs consumption was associated with higher psychological distress, higher HI with severe and moderate intensity, and worse quality of life. Conversely, triptans consumption was correlated with HI of mild intensity, and problem-focused coping strategies. To conclude, the psychological profile, and in particular, the psychological distress and specific coping strategies might influence the self-management of acute medication., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Background: OnabotulinumtoxinA (BOTOX®, Allergan plc, Dublin, Ireland) is approved for the preventive treatment of headaches in adult patients with chronic migraine (CM) in Australia by the country's reimbursement mechanism for medicines, the Pharmaceutical Benefits Scheme (PBS). To our knowledge, this study represents the first focused report evaluating real-world evidence of onabotulinumtoxinA treatment via the PBS in Australian clinics., Methods: This study reviewed the medical records of adults with inadequately controlled CM from 7 private neurology practices in Australia who, beginning in March 2014, received PBS-subsidized onabotulinumtoxinA per product labelling for the first time. The primary effectiveness measure was the percentage of patients achieving a response defined by 50% or greater reduction in headache days from baseline after 2 treatment cycles. Additional data were recorded in the case report form when available and included demographics, clinical characteristics, headache severity and frequency, Headache Impact Test (HIT-6) score, medication use, and days missed of work or study at baseline, after 2 treatment cycles, and at last follow-up. Differences in mean changes from baseline were evaluated with a 1-tailed t-test or Pearson's chi-squared test (p < 0.05)., Results: The study population included 211 patients with a mean (SD) of 25.2 (5.3) monthly headache days at baseline. In the primary outcome analysis, 74% of patients achieved a response, with a mean (SD) of 10.6 (7.9) headache days after 2 treatment cycles (p < 0.001). Secondary effectiveness outcomes included mean (SD) reductions in HIT-6 score of - 11.7 (9.8) and - 11.8 (12.2) after 2 treatment cycles (p < 0.001) and final follow-up (p < 0.001), respectively, and mean (SD) decreases in days per month of acute pain medication use of - 11.5 (7.6) after 2 treatment cycles (p < 0.001) and - 12.7 (8.1) at final follow-up (p < 0.001)., Conclusion: This study provides additional clinical evidence for the consistent effectiveness of onabotulinumtoxinA for the treatment of CM in Australia. This effectiveness was made evident by reductions in migraine days, severe headache days, and HIT-6 scores from baseline.

Objective: To investigate the effect of the H 1 -antihistamine clemastine on the migraine-inducing abilities of pituitary adenylate cyclase activating peptide-38., Methods: We conducted a double-blind, randomized, placebo controlled two-way cross-over study. Twenty migraine without aura patients were randomly allocated to receive bolus clemastine 2 mg (1 mg/ml) or bolus saline 2 ml intravenously over 2 min on two study days. Following each bolus injection, 10 pmol/kg/min of pituitary adenylate cyclase activating peptide-38 was administered intravenously over 20 min. We recorded migraine/headache characteristics every 10 min until 90 min after the start of infusion, and collected blood to investigate mast cell degranulation and the inflammation markers tryptase and tumor necrosis factor-alpha before and after infusion of pituitary adenylate cyclase activating peptide-38., Results: After clemastine pretreatment, five out of 20 participants developed a migraine-like attack in response to a pituitary adenylate cyclase activating peptide-38 infusion compared to nine out of 20 after placebo pretreatment ( p = 0.288). Following clemastine pretreatment, 15 out of 20 participants reported headache in response to a pituitary adenylate cyclase activating peptide-38 infusion, whereas 19 out of 20 participants did so following placebo pretreatment ( p = 0.221). We found no difference in area under the curve 12 h for headache intensity between the two experimental days ( p = 0.481). We found no difference in area under the curve 180 min for tryptase ( p = 0.525) or tumor necrosis factor-alpha ( p = 0.487) between clemastine and placebo pretreatment days., Conclusion: H 1 -antihistamine, clemastine, failed to prevent migraine or headache after pituitary adenylate cyclase activating peptide-38 infusion, thus making a role for histamine release or mast cell degranulation in pituitary adenylate cyclase activating peptide-38-induced migraine less likely.

Background: Children with Sturge-Weber syndrome can experience severe headache with or without transient hemiparesis. Flunarizine, a calcium antagonist, has been used for migraine. The experience with flunarizine for headache in a cohort of children at a national center for Sturge-Weber syndrome is reviewed, reporting its efficacy and adverse effect in this population., Methods: We collected data from health care professionals' documentation on headache (severity, frequency, duration) before and on flunarizine in 20 children with Sturge-Weber syndrome. Adverse effects reported during flunarizine treatment were collated. The Wilcoxon signed rank test was used to determine the significance of pre- versus post-treatment effect., Results: Flunarizine was used for headache alone (13) or mixed migrainous episodes and vascular events (7). The median duration of treatment was 145 days (range 43 to 1864 days). Flunarizine reduced headache severity (z = -3.354, P = 0.001), monthly frequency (z = -2.585, P = 0.01), and duration (z = -2.549, P = 0.01). Flunarizine was discontinued owing to intolerable adverse effects in a minority (2). Sedation and weight gain were the most common side effects. There were no reports of behavior change or extrapyramidal features., Conclusions: The most effective management for headaches in patients with Sturge-Weber syndrome has not been established. This retrospective observational study found benefit of flunarizine prophylaxis on headache severity, frequency, and duration in children with Sturge-Weber syndrome without severe side effects. Flunarizine is not licensed for use in the United Kingdom, but these data support its off-license specialist use for headache prophylaxis in Sturge-Weber syndrome., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Migraine has a substantial impact on daily living, affecting productivity and quality of life for patients and their families. Patients frequently discontinue preventive medications in part because of a delay in headache and symptom relief due to the long dose titration procedures necessary for some migraine preventives., Objective: To evaluate the efficacy of fremanezumab, a selective monoclonal CGRP ligand antibody, during the first 3 weeks of therapy in patients with high-frequency episodic migraine (HFEM) to relieve migraine headaches and associated symptoms and to reduce use of acute migraine medications., Methods: In a multicenter, randomized, double-blind, placebo-controlled, phase 2 study, patients with HFEM who met inclusion criteria and were 80% compliant with daily headache diary entry were randomized and treated once every 28 days for 3 months with either placebo or fremanezumab 225 or 675 mg. Compared to placebo, both doses of fremanezumab significantly reduced the primary endpoint of the HFEM study, change in the number of migraine days in month 3 relative to baseline. Herein, we performed post-hoc analyses to assess the efficacy of each dose during the first 3 weeks of treatment to reduce migraine headache parameters, associated migraine symptoms, and the consumption of acute migraine medications., Results: The sample consisted of 297 study participants. Compared to placebo, decreases in migraine days were seen during the first week of therapy for both fremanezumab doses with least square mean (LSM) differences between fremanezumab 225 mg and placebo of -0.93 (95% CI: -1.36, -0.49) and between 675 mg dose and placebo of -1.02 (95% CI: -1.46, -0.58), both P < .0001. This benefit was maintained through the second week of therapy for the 225 and 675 mg doses, respectively, (-0.76 (95% CI: -1.11, -0.40) P < .0001, -.79 (95% CI: -1.15, -0.44) P < .0001) and the third week of therapy (-0.64 (95% CI: -0.97, -0.30) P = .0003 and -0.64 (95% CI: -0.98, -0.30) P = .0003). Likewise in the first week, patients recorded reductions in associated migraine symptoms such as nausea, vomiting, photophobia, and phonophobia, which continued through weeks 2 and 3. There were also reductions in days with acute medication use to treat migraine for the 225 and 675 mg fremanezumab doses compared to placebo. In the first week, LSM differences between 225 mg and placebo were -1.02 (95% CI: -1.39, -0.64) and between 675 mg and placebo were -1.06 (95% CI: -1.39, -0.64) P < .0001); for the second and third weeks (-1.01 (95% CI: -1.14, -0.55) P < .0001; -.90 (95% CI: -1.04, -0.44) P < .0001; -.91 (95% CI: -0.92, -0.34) P < .0001; and -.83 (95% CI: -0.84, -0.26) P = .0002), respectively., Conclusion: Fremanezumab treatment resulted in a rapid preventive response in patients with HFEM, with reductions seen in several headache parameters and migraine symptoms within the first week after therapy initiation and continuing during the second and third weeks. Patients also were able to rapidly reduce their use of acute medications to treat migraine attacks. The trial is registered at Clinicaltrials.gov as NCT02025556., (© 2018 American Headache Society.)

Competing Interests: J.-C. Cuvellier déclare participer ou avoir participé à des interventions ponctuelles pour l’entreprise Novartis.

Study Objective: Migraine patients continue to report headache during the days and weeks after emergency department (ED) discharge. Dexamethasone is an evidence-based treatment of acute migraine that decreases the frequency of moderate or severe headache within 72 hours of ED discharge. We hypothesize that intramuscular methylprednisolone acetate, a long-acting steroid that remains biologically active for 14 days, will decrease the number of days with headache during the week after ED discharge by at least 1 day compared with intramuscular dexamethasone., Methods: We conducted a randomized, blinded clinical trial comparing intravenous metoclopramide at 10 mg+intramuscular dexamethasone at 10 mg with intravenous metoclopramide at 10 mg+intramuscular methylprednisolone acetate at a dose of 160 mg for patients presenting to 2 different EDs with moderate or severe migraine. Outcomes were assessed by telephone with a standardized instrument. The primary outcome was number of days with headache during the week after ED discharge. Secondary outcomes were complete freedom from headache, without the necessity of additional headache medication for the entire week after ED discharge, and medication preference, as determined by asking the patient whether he or she would want to receive the same medication again., Results: One hundred nine patients received dexamethasone and 111 received methylprednisolone acetate. We obtained primary outcome data from 101 dexamethasone patients and 106 methylprednisolone acetate patients. Dexamethasone patients reported 3.0 headache days and methylprednisolone acetate 3.3 headache days (95% confidence interval for rounded mean difference of 0.4 days: -0.4 to 1.1). Of 107 dexamethasone patients with analyzable data, 10 (9%) reported complete freedom from headache at 1 week versus 6 of 110 (5%) methylprednisolone acetate patients (95% confidence interval for difference of 4%: -3% to 11%). In the dexamethasone group, 76 of 101 (75%) patients would want the same medication again versus 75 of 106 (71%) of methylprednisolone acetate patients (95% confidence interval for difference of 4%: -8% to 17%). Other than injection site reactions, which were more common in the methylprednisolone acetate group, there were no substantial differences in frequency of adverse events., Conclusion: Methylprednisolone acetate does not decrease the frequency of post-ED discharge headache days compared with dexamethasone. Most migraine patients are likely to continue to experience headache during the week after ED discharge., (Copyright © 2018 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Hemodialysis (HD) may have some adverse effects on the nervous system. Headache is the most commonly reported neurological symptom amongst HD patients. Our aim was to determine the frequency, clinical characteristics and triggering factors of HD-related headache (HRH) and to evaluate preventive strategies for reducing HRH., Method: In all, 494 patients were included. Comparative controls (CC) were classified within the same patients without headache. Arterial systolic/diastolic blood pressure, blood urea nitrogen (BUN) and creatinine were correlated before/after one HD. The urea reduction ratio during the dialysis session was determined., Results: A total of 175 patients (35.4%) with a mean age of 57.3 ± 15.7 years were diagnosed with HRH. HRH was more common in males (P < 0.001). Headache was started a mean of 2.90 ± 0.86 h after the HD. The common localization of pain was reported to be bifrontal in 41.7% (n = 73). The mean duration of headache was 6.22 ± 7.8 h, with a duration of ≤4 h reported by 64.0% of patients. The mean Visual Analog Scale score was 5.64 ± 2.05. The differences between pre/post-dialysis BUN values were 94.6 ± 31.1 in HRH patients and 86.8 ± 28.5 in the CC group (P = 0.006). The systolic blood pressure difference between the pre/post-dialysis measurements was 22.4 ± 16.5 mmHg in HRH patients and 12.8 ± 19.4 mmHg in CC(P < 0.001). Patients with HRH had significantly higher mean systolic and diastolic blood pressure pre-dialysis values (systolic, P = 0.002; diastolic, P < 0.001). The differences in systolic/diastolic blood pressure between pre/post-dialysis were higher in the HRH group (P < 0.001, P = 0.001, respectively)., Conclusion: Regulating the frequency and timing of dialysis may provide better management in HRH with high BUN levels and high pre-dialysis blood pressure., (© 2018 EAN.)

Background: Primary headaches can be reduced by lifestyle changes, such as stress management and physical activity. However, access to programs focused on behavioral interventions is limited in underserved, poor communities., Objectives: We performed a randomized open-label clinical trial to test the therapeutic and behavioral effects of aerobic exercise, relaxation, or the combination of both, in individuals with primary headaches of a small, low-income community of the Brazilian Amazon., Methods: Participants were screened from the riverine/rural population, and individuals with primary headache were included. We assessed clinical characteristics and physical activity levels. Interventions were delivery 3 times/week for 6 months. The primary outcome variable was changes in days with headache, while changes in duration of attacks, pain intensity, and physical activity levels were secondary outcomes variables., Results: Seven hundred and ninety individuals were screened (15.3% of rural/riverine population). Seventy-four participants were randomly assigned to relaxation (n = 25), physical activity orientation program (n = 25), or both (n = 24) interventions. Intention to treat analyses showed all interventions as effective to reduce days with headaches and duration of attacks (both P < .01). Pain intensity was reduced only in relaxation and relaxation + physical activity groups (both P < .01). Physical activity levels increased only in the relaxation + physical activity group (P < .05)., Conclusions: Non-pharmacological interventions such as physical activity and relaxation are effective for reducing headaches, while combining such interventions promote health behavior toward higher physical activity levels in low-income populations with primary headaches., Clinical Trial Registration Number: SGPP 1544., (© 2018 American Headache Society.)

Headache is a neurologic disorder that displays gender dichotomy. It is well established that there is a strong link between migraine headache and sex hormones, specifically estrogen, which influences the severity of migraines during the menstrual cycle, pregnancy, and menopause. Furthermore, the epidemiology of headaches during pregnancy and the postpartum period is very distinct from that in males or nonpregnant females, in part due to the hemodynamic and hematologic changes that occur during pregnancy. These changes put women at higher risk for cerebral venous thrombosis, hemorrhagic stroke, and hypertensive disorders of pregnancy like preeclampsia, eclampsia, posterior reversible encephalopathy syndrome, and reversible cerebral vasoconstriction syndrome. Headache in pregnancy and the puerperium can be a cause of heightened anxiety in most women, who are concerned not only about the effect of the headache itself on the pregnancy but also about the effect of the treatment options on the pregnancy and the fetus. In this review, we discuss the latest literature on type and distribution of headaches during pregnancy and the postpartum period, and provide a digestible overview of the safety profile of commonly used abortive and prophylactic medications. We also discuss important considerations when treating migraine during menopause., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: Adolescent girls frequently suffer from temporomandibular disorder (TMD) symptoms and associated headache. A program aimed at informing about risk behavior for TMD symptoms, how to influence harmful habits and about general relaxation was tested., Material and Methods: Eighty girls at two high schools, 16 years of age, with or without symptoms, were invited to the health information on two occasions and 60 girls participated. Firstly, a questionnaire regarding symptoms and oral parafunctional habits was administrated. Structured information was given about the normal anatomy and function of muscles and joints, about the occlusion, oral habits and symptoms of orofacial pain/dysfunction and headache. General relaxation was instructed and trained. At a three-month follow-up, the same questionnaire regarding symptoms as at baseline was completed., Result: The information provided was perceived as useful and instructive. At the follow-up, 77% reported that they used what they had learned. Headache once a week or more decreased from 49% at baseline to 35% and headache 'never/rarely' changed from 11% to 25% (p = .002). Reported joint sounds had decreased by the follow-up (p = .053), as had the use of chewing gum (p = .002). A majority of the girls suggested that the information should be scheduled during school hours., Conclusion: Health information about the jaw system can influence risk factors for TMD symptoms and the frequency of symptoms among adolescent girls.

Objective: To assess the headache patterns among medical students of Umm Al-Qura College of Medicine, Makkah, Kingdom of Saudi Arabia. Medical students represent a vulnerable group for primary headache disorders, as they are exposed to various physical and psychological stressors., Methods: We carried an observational, cross-sectional study, and collected data during February, 2017 using electronic questionnaires. The international classification of headache disorders, third edition (ICHD-3) beta edition was used to classify headache into 10 types., Results: A total of 623 responses (82.2%) were received out of 758 participants. The one-year headache prevalence was 558 (89.6%). The most common diagnosis among both genders was frequent tension-type headache (TTH) (n=173, 31.0%), followed by probable infrequent TTH (n=114, 20.4%) and probable frequent TTH (n=63, 11.3%). The greatest proportions of students who reported an impact of their academic level were found among the chronic TTH, migraine without and with aura (n=2, 40.0%; n=14, 34.4%; n=11, 33.3%). Migraine without aura was more prevalent among females (n=29, 10.5%) than males (n=10, 3.5%). Self-medication was common (62.5%-100.0%). Simple analgesics (67.4%-80.0%), sleeping (54.3%-80.0%) and caffeine intake (28.3%-60.0%) were the top 3 therapies that were practiced., Conclusion: The prevalence of headache among Umm Al-Qura university (UQU), Makkah, Kingdom of Saudi Arabia`s medical students appears higher than the prevalence among the general population. This may have a significant impact on academic performance and necessitates special attention. We recommend further studies on interventions to reduce the prevalence and impact of this prevalent problem.

We investigated the association of mean daily macronutrient intake with migraine and non-migraine headaches. This cross-sectional study included 8042 men and 23,728 women from the ongoing population-based NutriNet-Santé e-cohort. Headache status was assessed via an online self-report questionnaire (2013⁻2016). Migraine was defined using established criteria and dietary macronutrient intake was estimated via ≥3 24 h dietary records. Mean daily intake (g/day) of carbohydrates (simple, complex, and total), protein, and fat (saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, and total) were the main exposure variables. Adjusted gender-specific analysis of variance (ANOVA) models were fit. Presence of migraines was noted in 9.2% of men (mean age = 54.3 ± 13.3 years) and 25.7% of women (mean age = 49.6 ± 12.8 years). In adjusted models, we observed (1) somewhat lower protein ( p < 0.02) and higher total fat ( p < 0.01) intake among male migraineurs compared with males without headaches and those with non-migraine headaches; (2) somewhat higher total fat ( p < 0.0001) and total carbohydrate intake ( p < 0.05) among female migraineurs compared with females without headaches and those with non-migraine headaches. The findings, which provide preliminary support for modest gender-specific differences in macronutrient intake by migraine status, merit confirmation in different population-based settings, as well as longitudinally, and could help to inform future dietary interventions in headache prevention.

Background: Previous studies indicate that sumatriptan is not effective when second messenger levels are high as after cilostazol provocation. Therefore, we have conducted the present study, where sumatriptan is administrated as pretreatment before cAMP increases due to cilostazol intake. Our hypothesis was that pretreatment with sumatriptan would have a significant effect against cilostazol induced headache in healthy volunteers., Methods: In a double-blind, randomized, crossover design, 30 healthy volunteers of both sexes received cilostazol 200 mg on two separate days, each day preceded by oral sumatriptan (2 × 50 mg) or placebo. Headache response and accompanying symptoms were registered in a questionnaire by the participants themselves., Results: Cilostazol induced a mild to moderate headache in all but 3 participants (Range 0-7 on Numerical Rating Scale). There was no significant difference in headache score 2 h (p = 0.67) or 4 h (p = 0.1) after treatment between the 2 days. Median peak headache score was 1.5 (range 0-5) on the sumatriptan day and 2 (range 0-7) on the placebo day (p = 0.26)., Conclusion: Pre-treatment with sumatriptan prevents cilostazol induced headache from developing. However, the placebo group did not develop enough headache to get statistical significant results. The cilostazol pre-treatment model is valuable for experimental headache research and perhaps for testing drugs with another mechanism of action., Trial Registration: ClinicalTrials.gov Identifier: NCT03156920 .

The objective of this study was to assess whether dietary intake of long-chain omega-3 polyunsaturated fatty acids (PUFAs) is associated with lower prevalence of headache in the U.S., Population: This cross-sectional study used data for a nationally representative sample of 12,317 men and women aged ≥ 20 years participating in the National Health and Nutrition Examination Surveys of 1999-2004. Interviewers recorded self-report of severe headache or migraine in the past three months. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were quantified from 24-hour dietary recall using the U.S. Department of Agriculture National Nutrient Database. Serum concentration of C-reactive protein, a marker of inflammation and potential mediator of PUFA's analgesic properties, was quantified by latex-enhanced nephelometry. Multivariable generalized linear models estimated prevalence ratios (PR) with 95% confidence limits (CL) for severe headache or migraine adjusting for NHANES cycle, sociodemographic characteristics, body mass index and total energy intake. The unadjusted prevalence of severe headache or migraine was 22.0% (females 28.2%, males 15.5%). In multivariable analysis, greater intake of omega-3 PUFAs was associated with lower prevalence of severe headache or migraine: PR 0.94 (95% CL: 0.88, 0.99, p = 0.035) per log unit increase in EPA, and PR 0.94 (95% CL: 0.90, 0.99, p = 0.023) per log unit increase in DHA. The strength of association was greater for non-Mexican Hispanics than for other racial/ethnic groups but was not attenuated after adjustment for C-reactive protein. In conclusion, higher dietary intakes of EPA and DHA were associated with lower prevalence of headache supporting the hypothesis that omega-3 PUFAs may prevent or reduce headache., (Copyright © 2018. Published by Elsevier Ltd.)

Purpose: Nasal packing is an option for bleeding control after endoscopic sinus surgery and septoplasty. Although new packing materials have been developed, patients still suffer from pain and require additional analgesics treatments. In this study, a prospective, randomized, and double-blind controlled trial was designed to evaluate the effect of fentanyl-soaked packing on pain after endoscopic sinus surgery and septoplasty., Methods: One hundred fifty-two patients who underwent nasal surgeries due to chronic rhinosinusitis or nasal septal deviation were enrolled in this study. At the end of operation, 50 mcg fentanyl-soaked biodegradable synthetic polyurethane foams packing Nasopore or Merocel were applied to a group of 79 patients, and saline-soaked ones were applied to another group of 73 patients. To evaluate the influence of fentanyl on postoperative nasal pain, patients' conditions were assessed via means of Numeric Rating Scale, patient satisfaction, and Ramsay Sedation Scale. In addition, symptoms of headache or sore throat and any signs of cardiopulmonary-relevant indicators were monitored., Results: The fentanyl group had significantly decreased Numeric Rating Scale and increased patient satisfaction in every operation type for the majority of postoperative time periods ( P < .05) with reduced postoperative headache and sore throat compared to the control group. The fentanyl group showed a higher score on Ramsay Sedation Scale than the control group ( P < .05 in group including endoscopic sinus surgery). There were no significant differences in cardiopulmonary-relevant indicators between the 2 groups ( P > .05)., Conclusion: Fentanyl group showed significantly reduced postoperative pain without serious adverse effects. We suggest that topical fentanyl application to nasal packs can be a useful method to reduce pain during the early postoperative period after endoscopic sinus surgery and septoplasty.

Background: Computer users frequently complain about problems with seeing and functioning of the eyes. Asthenopia is a term generally used to describe symptoms related to (prolonged) use of the eyes like ocular fatigue, headache, pain or aching around the eyes, and burning and itchiness of the eyelids. The prevalence of asthenopia during or after work on a computer ranges from 46.3% to 68.5%. Uncorrected or under-corrected refractive error can contribute to the development of asthenopia. A refractive error is an error in the focusing of light by the eye and can lead to reduced visual acuity. There are various possibilities for optical correction of refractive errors including eyeglasses, contact lenses and refractive surgery., Objectives: To examine the evidence on the effectiveness, safety and applicability of optical correction of refractive error for reducing and preventing eye symptoms in computer users., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; Embase; Web of Science; and OSH update, all to 20 December 2017. Additionally, we searched trial registries and checked references of included studies., Selection Criteria: We included randomised controlled trials (RCTs) and quasi-randomised trials of interventions evaluating optical correction for computer workers with refractive error for preventing or treating asthenopia and their effect on health related quality of life., Data Collection and Analysis: Two authors independently assessed study eligibility and risk of bias, and extracted data. Where appropriate, we combined studies in a meta-analysis., Main Results: We included eight studies with 381 participants. Three were parallel group RCTs, three were cross-over RCTs and two were quasi-randomised cross-over trials. All studies evaluated eyeglasses, there were no studies that evaluated contact lenses or surgery. Seven studies evaluated computer glasses with at least one focal area for the distance of the computer screen with or without additional focal areas in presbyopic persons. Six studies compared computer glasses to other types of glasses; and one study compared them to an ergonomic workplace assessment. The eighth study compared optimal correction of refractive error with the actual spectacle correction in use. Two studies evaluated computer glasses in persons with asthenopia but for the others the glasses were offered to all workers regardless of symptoms. The risk of bias was unclear in five, high in two and low in one study. Asthenopia was measured as eyestrain or a summary score of symptoms but there were no studies on health-related quality of life. Adverse events were measured as headache, nausea or dizziness. Median asthenopia scores at baseline were about 30% of the maximum possible score.Progressive computer glasses versus monofocal glassesOne study found no considerable difference in asthenopia between various progressive computer glasses and monofocal computer glasses after one-year follow-up (mean difference (MD) change scores 0.23, 95% confidence interval (CI) -5.0 to 5.4 on a 100 mm VAS scale, low quality evidence). For headache the results were in favour of progressive glasses.Progressive computer glasses with an intermediate focus in the upper part of the glasses versus other glassesIn two studies progressive computer glasses with intermediate focus led to a small decrease in asthenopia symptoms (SMD -0.49, 95% CI -0.75 to -0.23, low-quality evidence) but not in headache score in the short-term compared to general purpose progressive glasses. There were similar small decreases in dizziness. At medium term follow-up, in one study the effect size was not statistically significant (SMD -0.64, 95% CI -1.40 to 0.12). The study did not assess adverse events.Another study found no considerable difference in asthenopia between progressive computer glasses and monofocal computer glasses after one-year follow-up (MD change scores 1.44, 95% CI -6.95 to 9.83 on a 100 mm VAS scale, very low quality evidence). For headache the results were inconsistent.Progressive computer glasses with far-distance focus in the upper part of the glasses versus other glassesOne study found no considerable difference in number of persons with asthenopia between progressive computer glasses with far-distance focus and bifocal computer glasses after four weeks' follow-up (OR 1.00, 95% CI 0.40 to 2.50, very low quality evidence). The number of persons with headache, nausea and dizziness was also not different between groups.Another study found no considerable difference in asthenopia between progressive computer glasses with far-distance focus and monofocal computer glasses after one-year follow-up (MD change scores -1.79, 95% CI -11.60 to 8.02 on a 100 mm VAS scale, very low quality evidence). The effects on headaches were inconsistent.One study found no difference between progressive far-distance focus computer glasses and trifocal glasses in effect on eyestrain severity (MD -0.50, 95% CI -1.07 to 0.07, very low quality evidence) or on eyestrain frequency (MD -0.75, 95% CI -1.61 to 0.11, very low quality evidence).Progressive computer glasses versus ergonomic assessment with habitual (computer) glassesOne study found that computer glasses optimised for individual needs reduced asthenopia sum score more than an ergonomic assessment and habitual (computer) glasses (MD -8.9, 95% CI -16.47 to -1.33, scale 0 to 140, very low quality evidence) but there was no effect on the frequency of eyestrain (OR 1.08, 95% CI 0.38 to 3.11, very low quality evidence).We rated the quality of the evidence as low or very low due to risk of bias in the included studies, inconsistency in the results and imprecision., Authors' Conclusions: There is low to very low quality evidence that providing computer users with progressive computer glasses does not lead to a considerable decrease in problems with the eyes or headaches compared to other computer glasses. Progressive computer glasses might be slightly better than progressive glasses for daily use in the short term but not in the intermediate term and there is no data on long-term follow-up. The quality of the evidence is low or very low and therefore we are uncertain about this conclusion. Larger studies with several hundreds of participants are needed with proper randomisation, validated outcome measurement methods, and longer follow-up of at least one year to improve the quality of the evidence.

Neck and shoulder stiffness is a typical subjective symptom in developed countries. This stiffness is caused by factors such as muscle tension and poor blood flow, leading to reduce work efficiency and diminish QOL. NKCP ® , a natto-derived dietary food supplement whose main component is bacillopeptidase F, has antithrombotic, fibrinolytic, and blood viscosity-lowering effects. Here, we investigated the effect of NKCP ® on neck and shoulder stiffness in a double-blind placebo-controlled randomized crossover study. Thirty subjects with neck and shoulder stiffness were randomly divided into 2 groups and ingested 250 mg of NKCP ® or placebo daily for 4 weeks. Headache score significantly improved in the NKCP ® group compared to the placebo group. Moreover, NKCP ® significantly improved the score of visual analogue scale for neck and shoulder stiffness and pain, reduced muscle stiffness of the neck, and increased the skin surface temperature of neck and shoulders, compared to before ingestion. No adverse effects were observed during this study. These results suggest that NKCP ® may alleviate headaches and chronic neck and shoulder stiffness and pain.

We estimated prevalence rates of complementary and alternative medicine (CAM) use by reason for use (treatment, wellness, or both), and examined perceived benefits of using CAM among U.S. adults with migraines/severe headaches. The 2012 National Health Interview Survey, which represents non-institutionalized adults with migraines/severe headaches (n = 4447 unweighted), were used. Of the study sample, 41.3% used some form of CAM in the past year. Nearly a third of them (29.6%) used CAM for wellness only and 59% used CAM for both wellness and treatment. In given six self-reported perceived benefits, those who used CAM for wellness only and for a combination of both treatment and wellness had higher likelihoods of reporting benefits for all categories (p < 0.05), except for better sleep, when compared to those who used CAM for treatment only. CAM use was associated with an improvement in several health-related quality of life outcomes in U.S. adults with migraines/severe headaches., (Copyright © 2017 Elsevier Ltd. All rights reserved.)