The effect of selenium supplementation on oxidative stress, clinical symptoms and mental health status in patients with migraine: a study protocol for a double-blinded randomized clinical trial.

BACKGROUND: Despite a number of recommended strategies, effective treatment of migraine remains elusive. Given the role of oxidative stress in the pathogenesis of migraine, selenium, as an antioxidant nutrient, may have a beneficial effect on migraine outcomes. However, no study has explored the effects of selenium supplementation on migraine symptoms, oxidative stress biomarkers, and mental health. Therefore, this randomized, double-blinded, placebo-controlled clinical trial aims to examine the effects of selenium supplementation among migraine patients. METHODS: Seventy-two migraine patients will receive either 200 µg/day selenium supplement (n = 36) or placebo (n = 36) for 12 weeks in a randomized, double-blinded, placebo-controlled study. The severity, frequency, and duration of headaches, mental health indices including depression, anxiety, and distress, and quality of life, as well as biomarkers of oxidative stress such as nitric oxide (NO), malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidant status (TOS), will be measured at the baseline and end of the study. The intention-to-treat (ITT) approach will be used to estimate missing values. One-way analysis of covariance (ANCOVA) will be performed to detect the effect of selenium supplementation on outcome variables. DISCUSSION: Oxidative stress is recognized as a key contributor to migraine pathogenesis. Selenium is an essential trace element with antioxidant properties, capable of crossing the blood-brain barrier (BBB), holding promise to alleviate the oxidative stress and neurotoxicity. Thus, selenium may beneficially affect clinical symptoms and oxidative stress as well as the quality of life in migraine patients. TRIAL REGISTRATION: This trial was registered in the Iranian Registry of Clinical Trials ( https://www.irct.ir/ ) on 27 May 2023 with the code number IRCT20121216011763N60.

A Role for Visual Art Therapy in the Management of Migraine.

PURPOSE OF REVIEW: Migraine is a disabling disorder that adversely affects the whole person and requires multimodal management. Through a brief historical overview of migraine as a subject for visual art, benefits reported from art therapy used in the management of other types of chronic pain, and a summary of the limited research involving art therapy for migraine, we aim to provide support for art therapy's potential role in the management of migraine. RECENT FINDINGS: As art therapy has been shown to be effective in the management of other chronic pain conditions, providing insight into the individual's pain experience and perception of pain, ameliorating pain by means of distraction, and improving psychosocial health, by extension, it may be of benefit in the migraine population as well. Migraine is disabling, and previous literature has shown efficacy in lifestyle modifications as well as complementary and alternative medicine. Based on its efficacy in other pain conditions, we suggest art therapy as an additional tool for the preventive management of migraine.

High Dosage Omega-3 Fatty Acids Outperform Existing Pharmacological Options for Migraine Prophylaxis: A Network Meta-Analysis.

Migraine is a highly prevalent neurologic disorder with prevalence rates ranging from 9% to 18% worldwide. Current pharmacologic prophylactic strategies for migraine have limited efficacy and acceptability, with relatively low response rates of 40% to 50% and limited safety profiles. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are considered promising therapeutic agents for migraine prophylaxis. The aim of this network meta-analysis (NMA) was to compare the efficacy and acceptability of various dosages of EPA/DHA and other current Food and Drug Administration-approved or guideline-recommended prophylactic pharmacologic interventions for migraine. Randomized controlled trials (RCTs) were eligible for inclusion if they enrolled participants with a diagnosis of either episodic or chronic migraine. All NMA procedures were conducted under the frequentist model. The primary outcomes assessed were 1) changes in migraine frequency and 2) acceptability (i.e., dropout for any reason). Secondary outcomes included response rates, changes in migraine severity, changes in the frequency of using rescue medications, and frequency of any adverse events. Forty RCTs were included (N = 6616; mean age = 35.0 y; 78.9% women). Our analysis showed that supplementation with high dosage EPA/DHA yields the highest decrease in migraine frequency [standardized mean difference (SMD): -1.36; 95% confidence interval (CI): -2.32, -0.39 compared with placebo] and the largest decrease in migraine severity (SMD: -2.23; 95% CI: -3.17, -1.30 compared with placebo) in all studied interventions. Furthermore, supplementation with high dosage EPA/DHA showed the most favorable acceptability rates (odds ratio: 1.00; 95% CI: 0.06, 17.41 compared with placebo) of all examined prophylactic treatments. This study provides compelling evidence that high dosage EPA/DHA supplementation can be considered a first-choice treatment of migraine prophylaxis because this treatment displayed the highest efficacy and highest acceptability of all studied treatments. This study was registered in PROSPERO as CRD42022319577.

Effects of Introvision, a self-regulation method with a mindfulness-based perception technique in migraine prevention: a monocentric randomized waiting-list controlled study (IntroMig Study).

BACKGROUND: Migraine is a brain disorder with recurrent headache attacks and altered sensory processing. Introvision is a self-regulation method based on mindfulness-like perception techniques, developed at the University of Hamburg. Here, we examined the effect of Introvision in migraine prevention. METHODS: Migraineurs with at least five headache days per month were block-randomized to the experimental group (EG) or waiting list group (WL), the latter starting Introvision training six weeks after the EG. Participants learned Introvision in six weekly on-site group sessions with video-conference support followed by three individual video-conference sessions. Headache diaries and questionnaires were obtained before Introvision training and three months after the last individual Introvision session. RESULTS: Fifty-one patients completed the study. The primary outcome, headache days of the EG after Introvision training compared to those of the WL before the training, showed no significant effect (10.6 ± 7.7, n = 22; vs. 10.9 ± 6.3, n = 29, p = 0.63; Mann-Whitney-U-Test). The secondary outcome, comparing pooled EG and WL data before and after Introvision training, revealed a significant reduction of headache days (from 11.7 ± 6.5 to 9.8 ± 7.0; p = 0.003; Wilcoxon-paired-Test) as well as of acute medication intake and Headache-Impact-Test 6 (HIT-6) scores and increased self-efficacy as quantified by increased FKMS-scores (FKMS: german short form of the Headache Management Self-Efficacy Scale (HMSE)). CONCLUSION: Although the study did not reach its primary endpoint, several secondary outcome parameters in the pooled (non-controlled) pre-post analysis showed an improvement with a decrease in monthly headache days by 1.9 days/ month. A larger randomized controlled trial has to corroborate these preliminary findings. TRIAL REGISTRATION: NCT03507400, Registration date 09.03.2018.

Effectiveness of Mindfulness-Based Stress Reduction as a Nondrug Preventive Intervention in Patients with Migraine: A Systematic Review with Meta-Analyses.

INTRODUCTION: Migraine is a neurological disorder characterized by recurrent, severe headaches that are often accompanied by other symptoms. There are various factors that can trigger a migraine in sufferers. Stress can be such a trigger. Drug and nondrug treatments are available for the preventive treatment of migraine. According to a German guideline, mindfulness can be recommended for the prophylaxis of migraine. Therefore, the aim was to investigate the effectiveness of mindfulness-based stress reduction (MBSR) in relation to patient-relevant outcomes in adult patients with migraine. Patient-relevant outcomes in this context are migraine frequency, headache intensity during a migraine attack, depressive symptoms, and quality of life. MATERIAL AND METHODS: The conduct of this study was guided by the PRISMA 2020 statement. A systematic literature search for randomized controlled trials (RCTs) of the effectiveness of MBSR in adult migraine patients was conducted in December 2021 in three databases: MEDLINE via PubMed, the Cochrane Library, and Web of Science. In addition, a review of reference lists and a search of study registries were performed. The last search was conducted on October 7, 2022. In a two-step process, studies were selected based on predefined inclusion and exclusion criteria. The potential for bias was assessed using the Cochrane Risk of Bias Tool 2. The results were summarized descriptively and by means of quantitative synthesis. RESULTS: Four RCTs with a total of 275 patients and the follow-up publication of one of these studies were included. The risk of bias in one study each was judged to be low or of some concern and high in two studies. Four studies were included in the quantitative analysis. For the endpoint migraine frequency, the meta-analytic summary of three studies failed to show a statistically significant benefit for MBSR (SMD: -0.23; 95% CI: -0.79 to 0.32). For the endpoint depressive symptoms, a meta-analytic summary of three studies showed a statistically significant benefit for MBSR (SMD: -0.59; 95% CI: -0.93 to -0.25). No study had examined the severity of headaches during a migraine episode. CONCLUSION: Some results suggest that migraine patients may benefit from MBSR. However, the evidence base is currently insufficient for recommendations on the use of MBSR as a nondrug treatment option. Further adequately powered, high-quality RCTs are needed.Migräne ist eine neurologische Erkrankung, die durch wiederkehrende, starke Kopfschmerzen gekennzeichnet ist, die häufig von anderen Symptomen einhergehen. Es gibt verschiedene Faktoren, die bei den Betroffenen eine Migräne auslösen können. Ein solcher Auslöser kann Stress sein. Für die präventive Behandlung der Migräne stehen medikamentöse und nichtmedikamentöse Verfahren zur Verfügung. Laut einer deutschen Leitlinie kann Achtsamkeit zur Prophylaxe von Migräne empfohlen werden. Ziel der Studie war es daher, die Wirksamkeit von achtsamkeitsbasierter Stressreduktion (MBSR) in Bezug auf patientenrelevante Outcomes bei erwachsenen Migränepatienten zu untersuchen. Patientenrelevante Outcomes in diesem Zusammenhang sind Migränehäufigkeit, Kopfschmerzintensität während einer Migräneattacke, depressive Symptome und Lebensqualität.Die Durchführung dieser Studie orientierte sich am PRISMA-Statement. Eine systematische Literatursuche nach randomisierten kontrollierten Studien zur Wirksamkeit von MBSR bei erwachsenen Migränepatienten wurde im Dezember 2021 in drei Datenbanken durchgeführt: MEDLINE über PubMed, die Cochrane Library und Web of Science. Darüber hinaus wurden Referenzlisten und Studienregister durchsucht. Die letzte Suche erfolgte am 7. Oktober 2022. In einem zweistufigen Verfahren wurden die Studien anhand von vordefinierten Ein- und Ausschlusskriterien ausgewählt. Das Verzerrungspotential der Studien wurde mit dem Cochrane Risk of Bias Tool 2 bewertet. Die Ergebnisse wurden deskriptiv und mit Hilfe einer quantitativen Synthese zusammengefasst.Es wurden vier randomisiert-kontrollierte Studien mit insgesamt 275 Patienten und die Nachfolgepublikation einer dieser Studien eingeschlossen. Das Verzerrungspotential wurde bei je einer Studie als gering oder bedenklich und bei zwei Studien als hoch eingestuft. Vier Studien wurden in die quantitative Analyse einbezogen. Für den Endpunkt Migränehäufigkeit ergab die metaanalytische Zusammenfassung von drei Studien keinen statistisch signifikanten Vorteil für MBSR (SMD −0.23; 95% CI −0.79 bis 0.32). Für den Endpunkt depressive Symptome zeigte eine metaanalytische Zusammenfassung von drei Studien einen statistisch signifikanten Vorteil für MBSR (SMD −0.59; 95% CI −0.93 bis −0.25). Keine Studie hatte die Schwere der Kopfschmerzen während einer Migräneepisode untersucht.Einige Ergebnisse deuten darauf hin, dass Migränepatienten von MBSR profitieren können. Allerdings ist die Evidenzbasis derzeit nicht ausreichend, um Empfehlungen für den Einsatz von MBSR als nichtmedikamentöse Behandlungsoption abzuleiten. Es werden daher weitere qualitativ hochwertige randomisiert-kontrollierte Studien mit ausreichender statistischer Power benötigt.

Placebo response in sham-acupuncture-controlled trials for migraine: A systematic review and meta-analysis.

AIM: To understand the placebo response of acupuncture and its effect on migraine and optimize the design of future acupuncture clinical trials on migraine treatment. METHODS: Randomized controlled trials with sham acupuncture as a control in migraine treatment were searched in four English databases from inception to September 1, 2022. The primary outcome was placebo response rate. Secondary outcomes were migraine symptoms, emotional condition, and quality of life. Factors associated with placebo response were also explored. Results were combined using risk difference (RD) or standardized mean difference (SMD) and 95% confidence interval (CI) with a random effects model. RESULTS: The final analysis included 21 studies involving 1177 patients. The pooled response rate of sham acupuncture was 0.34 (RD, 95% CI 0.23-0.45, I2 89.8%). The results (SMD [95% CI]) showed significant improvements in migraine symptoms (pain intensity -0.56 [-0.73 to -0.38], and episode conditions -0.55 [-0.75 to -0.35]); emotional condition (anxiety scale -0.49 [-0.90 to -0.08] and depression scale -0.21 [-0.40 to -0.03]); and quality of life on the Migraine-Specific Quality-of-Life Questionnaire (restrictive 0.78 [0.61-0.95]; preventive 0.52 [0.35-0.68]; and emotional 0.45 [0.28-0.62]) and on the Medical Outcomes Study Short-Form (physical 0.48 [0.34-0.62] and mental 0.21 [0.02-0.41]). Only acupuncture treatment frequency had a significant impact on the placebo response rate (RD 0.49 vs. 0.14; p = 0.00). CONCLUSIONS: The effect sizes for placebo response of sham acupuncture varied across migraine treatment trials. Further studies should routinely consider adjusting for a more complete set of treatment factors.

Tai Chi for the prophylaxis of episodic migraine: protocol of a non-inferiority randomized controlled trial with mechanism exploration.

BACKGROUND: Migraine is a complex neurovascular disorder with considerable clinical, social and economic issues. Tai chi has the potential to be an alternative prophylactic treatment for migraine with high safety since the adverse effects and limited efficacy of available medications. AIMS: The proposed study aims to compare the prophylaxis efficacy of 24-week Tai Chi training on migraine attacks with the standard prophylactic medication; and to explore the mechanism of Tai Chi in preventing migraine attacks by analyzing the associations between changes of migraine attacks and changes of neurovascular functions and inflammatory makers. METHOD: This is a two-arm parallel non-inferiority randomized controlled trial. In total 220 Hong Kong Chinese women aged 18-65 years with diagnosis of episodic migraine will be recruited and randomized to either the Tai Chi training group or the standard prophylactic medication group with 1:1 ratio, and receive the 24 weeks of modified 33-short form Yang-style Tai Chi training and the standard prophylactic medications, respectively. A 24-week follow-up will be implemented for both groups. For efficacy examination, the primary outcome was the frequency of migraine attacks measured by the migraine diary; and for the mechanism exploration, the primary outcome was the volume and number of white matter hyperintensity (WMH) measured by magnetic resonance imaging (MRI). The measurements will be conducted at the baseline, 24th weeks, and 48th weeks. Linear mixed model will be adopted to comprehensively analyze the changes of variables within and between groups. DISCUSSION: Given the importance of reducing disease burden and financial cost of migraine attacks, the findings of this study will provide new insights regarding the role of Tai Chi in alleviating migraine burden and further shed light on the mechanism action of Tai Chi on preventing headache attacks. TRIAL REGISTRATION: ClinicalTrials.gov NCT05690737. Registered on January 28, 2023.

Antiseizure medications as migraine preventatives: a call for action for a teratogenic and neurodevelopmental risk removal.

INTRODUCTION: A recent study has demonstrated an increased risk of neurodevelopmental disorders, including autism spectrum disorder, in individuals exposed to either valproate or topiramate monotherapy. Regulatory bodies have initiated a review to reassess the safety of topiramate exposure during pregnancy. These novel findings raise concerns regarding the recommendation of antiseizure medications in women of childbearing potential. This manuscript highlights current research defining concerns specific to the use of valproate and topiramate in women of childbearing potential. AREAS COVERED: This manuscript summarizes recent findings regarding the safety of valproate and topiramate when compared to alternative therapies for the preventative treatment of migraine in women of childbearing potential. The studies included in this review were selected following a comprehensive literature review of multiple relevant databases. All studies that were published within the past 15 years were considered for inclusion. EXPERT OPINION: The use of valproate and topiramate in women of childbearing potential should be highly discouraged. Our recommendations include a review of current prescribing guidelines, further public education regarding the neurodevelopmental and congenital risks associated with the use of valproate and topiramate, and an appeal for further research defining the safety of alternative medications for migraine prevention when intrauterine exposure is possible.

Non-pharmacological interventions for prophylaxis of vestibular migraine.

BACKGROUND: Vestibular migraine is a form of migraine where one of the main features is recurrent attacks of vertigo. These episodes are often associated with other features of migraine, including headache and sensitivity to light or sound. These unpredictable and severe attacks of vertigo can lead to a considerable reduction in quality of life. The condition is estimated to affect just under 1% of the population, although many people remain undiagnosed. A number of interventions have been used, or proposed to be used, as prophylaxis for this condition, to help reduce the frequency of the attacks. Many of these interventions include dietary, lifestyle or behavioural changes, rather than medication.  OBJECTIVES: To assess the benefits and harms of non-pharmacological treatments used for prophylaxis of vestibular migraine. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 23 September 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs in adults with definite or probable vestibular migraine comparing dietary modifications, sleep improvement techniques, vitamin and mineral supplements, herbal supplements, talking therapies, mind-body interventions or vestibular rehabilitation with either placebo or no treatment. We excluded studies with a cross-over design, unless data from the first phase of the study could be identified.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were: 1) improvement in vertigo (assessed as a dichotomous outcome - improved or not improved), 2) change in vertigo (assessed as a continuous outcome, with a score on a numerical scale) and 3) serious adverse events. Our secondary outcomes were: 4) disease-specific health-related quality of life, 5) improvement in headache, 6) improvement in other migrainous symptoms and 7) other adverse effects. We considered outcomes reported at three time points: < 3 months, 3 to < 6 months, > 6 to 12 months. We used GRADE to assess the certainty of evidence for each outcome.  MAIN RESULTS: We included three studies in this review with a total of 319 participants. Each study addressed a different comparison and these are outlined below. We did not identify any evidence for the remaining comparisons of interest in this review.   Dietary interventions (probiotics) versus placebo We identified one study with 218 participants (85% female). The use of a probiotic supplement was compared to a placebo and participants were followed up for two years. Some data were reported on the change in vertigo frequency and severity over the duration of the study. However, there were no data regarding improvement of vertigo or serious adverse events. Cognitive behavioural therapy (CBT) versus no intervention One study compared CBT to no treatment in 61 participants (72% female). Participants were followed up for eight weeks. Data were reported on the change in vertigo over the course of the study, but no information was reported on the proportion of people whose vertigo improved, or on the occurrence of serious adverse events.  Vestibular rehabilitation versus no intervention The third study compared the use of vestibular rehabilitation to no treatment in a group of 40 participants (90% female) and participants were followed up for six months. Again, this study reported some data on change in the frequency of vertigo during the study, but no information on the proportion of participants who experienced an improvement in vertigo or the number who experienced serious adverse events.  We are unable to draw meaningful conclusions from the numerical results of these studies, as the data for each comparison of interest come from single, small studies and the certainty of the evidence was low or very low.  AUTHORS' CONCLUSIONS: There is a paucity of evidence for non-pharmacological interventions that may be used for prophylaxis of vestibular migraine. Only a limited number of interventions have been assessed by comparing them to no intervention or a placebo treatment, and the evidence from these studies is all of low or very low certainty. We are therefore unsure whether any of these interventions may be effective at reducing the symptoms of vestibular migraine and we are also unsure whether they have the potential to cause harm.

External trigeminal neurostimulation in patients with chronic migraine.

Aim: To assess the safety and efficacy of external trigeminal neurostimulation (e-TNS) as an add-on treatment in chronic migraine (CM) prophylaxis. Materials & methods: A prospective observational open-label study was conducted on CM patients observed at baseline and 3 months after starting daily sessions of 20 min with e-TNS (Cefaly®). Results: A total of 24 volunteers affected by CM according to the ICHD-3 were included. At the 3 month follow-up, a >30% reduction of headache days was observed in four (16.5%) of 24 patients; a marginal headache improvement was observed in ten (42%) patients, with no or minor adverse effects (four of 24 patients). Conclusion: e-TNS may constitute a safe preventive treatment in CM, its limited efficacy is not statistically significant.

Migraine is one of the most prevalent and disabling diseases in the world. In chronic migraine cases, patients have headache ≥15 days/month, of which at least eight are migraines, for >3 months and often develop a medication overuse headache because of the excessive intake of drugs. Preventive therapies include, among others, peripheral nerve stimulation. In our study, 24 patients affected by chronic migraine were asked to use a peripheral nerve stimulation device (Cefaly^®) for 20 min daily for 3 months. During this period, we evaluated the efficacy and safety of the treatment using specific headache diaries in which patients collect information about their symptoms and disability. Our results show a limited and not statistically significant reduction in headache days in a group of patients ('responders') without serious adverse reactions.

L-arginine and aged garlic extract for the prevention of migraine: a study protocol for a randomised, double-blind, placebo-controlled, phase-II trial (LARGE trial).

BACKGROUND: Migraine is a common and distressing neurological condition characterised by recurrent throbbing headaches, nausea and heightened sensitivity to light and sound. Accumulating evidence suggests that cerebral arteries dilate during migraine, causing distal microvessels to constrict, which could activate nociceptors and cause onset of headache pain. If so, preventing or attenuating chronic microvascular constriction, and promoting a dilatory phenotype, may reduce frequency and/or severity of migraines. The primary aim of the L-Arginine and Aged Garlic Extract (LARGE) trial is to investigate whether oral treatment with dietary nutraceuticals, L-arginine and aged garlic extract (AGE), both systemic vasodilatory agents, will alleviate migraine frequency, duration and severity in adults with chronic frequent episodic migraines. METHODS: The study is a randomised double-blind placebo-controlled phase-II single-site clinical trial conducted in Perth, Australia. The target sample is to recruit 240 participants diagnosed with chronic frequent episodic migraines between 18 and 80 years of age. Participants will be randomised to one of four treatment groups for 14 weeks (placebo induction for 2 weeks, followed by 12 weeks on one of the respective treatment arms): placebo, L-arginine, AGE, or a combination of L-arginine and AGE. The doses of L-arginine and AGE are 1.5 g and 1 g daily, respectively. The primary outcome is to assess migraine response using change in migraine frequency and intensity between baseline and 12 weeks. Secondary outcomes include the impact of L-arginine and/or AGE on photosensitivity, retinal vessel changes, and blood biomarker concentrations of vascular tone, following a 12-week intervention. DISCUSSION: The protocol describes the oral administration of 2 nutraceutical-based interventions as possible prophylactic treatments for chronic frequent episodic migraines, with potential for direct clinical translation of outcomes. Potential limitations of the study include the fixed-dose design of each treatment arm and that in vivo neuroimaging methods, such as magnetic resonance imaging (MRI), will not be conducted to determine putative cerebro-vasodilatory changes to coincide with the outcome measures. Dose-response studies may be indicated. TRIAL REGISTRATION: The trial was retrospectively registered with the Australian New Zealand Clinical Trials Registry ACTRN12621001476820 (Universal Trial Number: U1111-1268-1117) on 04/08/2021. This is protocol version 1, submitted on 25/11/2022.

Matching adjusted indirect comparison of acupuncture versus fremanezumab in the preventive treatment of episodic migraine.

OBJECTIVE: Acupuncture and fremanezumab are second-line treatments for migraine prophylaxis. We aimed to compare acupuncture with fremanezumab in the preventive treatment of episodic migraine by using a matching-adjusted indirect comparison analysis (MAIC). METHODS: We acquired participant-level data from an acupuncture trial recruiting 302 participants and summary-level data from a fremanezumab trial recruiting 875 participants (290 participants received monthly fremanezumab [MF] and 291 received single-dose fremanezumab [SF]). The primary outcome was the mean reduction in monthly headache days. The secondary outcomes were the mean reduction in monthly moderate-to-severe headache days, days with acute medication, and the adverse events rate. RESULTS: Before matching, the acupuncture arm had significantly lower BMI, fewer headache days with at least moderate severity, and fewer days with acute medication. After matching, the baseline variables were comparable between groups. The three arms had no difference in the change of monthly migraine days (MF vs. acupuncture: mean difference 0.3, 95%CI -0.5 to 1.1, p-value = 0.473; SF vs. acupuncture: mean difference 0.5, 95%CI -0.3 to 1.3, p-value = 0.214). The results were similar in the analyses of secondary outcomes sensitivity analyses. Thirty-six (25%) participants in the acupuncture arm reported adverse events, versus 192(66%) participants in the MF arm and 193 (66%) in the SF arm. CONCLUSION: The preventive treatment effect of acupuncture is equivalent to fremanezumab, and it presented with a lower adverse event rate, which indicates that acupuncture can be an alternative to fremanezumab.

Nutritional intake of riboflavin (vitamin B2) and migraine: a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) 2001-2004.

OBJECTIVES: Clinical studies demonstrate that supplemental riboflavin is an efficacious and low risk prophylactic treatment for migraine. However, background riboflavin intake of adults with migraine from nutritional sources has not been evaluated. This study aimed to evaluate riboflavin consumption of adults with migraine in the United States, and further investigate the relationship between nutritional riboflavin consumption and the prevalence of migraine among adults. METHODS: This cross-sectional secondary analysis included 3439 participants ages 20-50 years old in the National Health and Nutrition Examination Survey from 2001 to 2004. Presence of migraine in the past three months was self-reported. Riboflavin intake was determined from one 24-hour recall interview. Odds ratios and 95% confidence intervals were calculated for riboflavin intake quartiles using an adjusted logistic regression model. Statistical significance was determined using an adjusted Wald test. RESULTS: Results showed that mean dietary consumption of riboflavin fulfilled the Recommended Dietary Allowance for migraine and control groups. Dietary riboflavin intake was associated with the odds of migraine (pWald = 0.002), but no association was found for supplemental or total riboflavin consumption (pWald = 0.479 and 0.136). When stratified by gender, there was no association of dietary riboflavin with migraine in males (pWald = 0.423), but an association was observed in females (pWald = 0.014). DISCUSSION: The RDA value for riboflavin was not relevant for assessing odds of migraine; however, differing odds of migraine were detected across dietary riboflavin consumption groups at levels above the RDA. Future riboflavin supplementation trials for migraine prophylaxis should consider measuring background dietary intake.

Efficacy and feasibility of a 12-week Tai Chi training for the prophylaxis of episodic migraine in Hong Kong Chinese women: A randomized controlled trial.

Background: Tai Chi has been broadly applied as alternative treatment for many neurological and psychological disorders. Whereas no study using Tai Chi as prophylactic treatment for migraine. The purpose of this study was to preliminarily examine the efficacy and feasibility of a 12-week Tai Chi training on migraine attack prevention in a sample of Chinese women. Methods: A two-arm randomized controlled trial was designed. Women aged 18 to 65 years and diagnosed with episodic migraine were randomized to either Tai Chi group (TC group) or the waiting list control group. A modified 33-short form Yang-style Tai Chi training with 1 h per day, 5 days per week for 12 weeks was implemented in the TC group, with a 12-week follow up period. The control group received a "delayed" Tai Chi training at the end of the trial. The primary outcome was the differences in attack frequency between 4 weeks before baseline and at the 9-12 weeks after randomization. The intensity and duration of headache were also measured. The feasibility was evaluated by the maintenance of Tai Chi practice and satisfactory level of the participants toward training. Results: Eighty-two women were randomized, finally 40 in TC group and 33 in control group were involved in the analysis. On average, women in TC group had 3.0 times (95% CI: -4.0 to -2.0, P < 0.01) and 3.6 days (95% CI: -4.7 to -2.5, P < 0.01) reduction of migraine attack per month. Compared with the control group, the differences were statistically significant (-3.7 attacks/month, 95% CI: -5.4 to -1.9; and -3.0 migraine days/month, 95% CI: -4.5 to -1.5; both P < 0.001). The intensity and duration of headache had 0.6 (95% CI: -1.2 to -0.0, P < 0.05) units and 1.2 (IQR: -5.0 to 1.1, P < 0.05) hours reduction in TC group, respectively. Most of the participants (69.2%-97.4%) were satisfied with the training. At the end of 24 weeks, on average, the participants maintained 1.5 times of practice per week and 20 min for each practice. Conclusion: The 12-week Tai Chi training significantly decreased the frequency of migraine attack. It was acceptable and practicable among female migraineurs. Clinical trial registration: www.ClinicalTrials.gov, identifier: NCT03015753.

2022 Taiwan Guidelines for Preventive Treatment of Migraine.

The Treatment Guideline Subcommittee of the Taiwan Headache Society evaluated the medications currently used for migraine prevention in Taiwan. The subcommittee assessed the results of recently published trials, meta-analyses, and guidelines. After expert panel discussions, the subcommittee reached a consensus on the preventive treatment of migraine in Taiwan, which includes recommendation levels, the strength of evidence, and essential prescription information (i.e., dosage and adverse effects) . The recent introduction of CGRP monoclonal antibodies has had a substantial effect on migraine treatment. Thus, the subcommittee updated the previous version of the treatment guideline published in 2017. Preventive medications for migraines can be divided into the following categories: ß-blockers, anticonvulsants, calcium channel blockers, antidepressants, onabotulinumtoxinA, anti-CGRP monoclonal antibodies, and complementary and alternative medicine. For episodic migraine prevention, propranolol, flunarizine, and topiramate are recommended as the first-line medications. Second-line medications for episodic migraine prevention include valproic acid, amitriptyline, and anti-CGRP monoclonal antibodies. Other treatment options could be used as third-line treatments. For chronic migraine prevention, topiramate, flunarizine, onabotulinumtoxinA, and anti-CGRP monoclonal antibodies are recommended as first-line therapies. Preventive medications for episodic migraine can also be used as second-line treatments for chronic migraine. For menstrual migraines, nonsteroidal anti-inflammatory drugs and triptans can be used for short-term prophylaxis. Indications for starting preventive treatment include a headache frequency of ≥4 days per month, profound disabilities, failure of or contraindication to acute therapies, a complicated migraine with debilitating (e.g., hemiplegic) auras, and migrainous brain infarction. The general principle for oral preventives is to "start low and go slow" while monitoring for adverse events and comorbid conditions. Physicians could consider gradually tapering the medications in patients with sustained improvement over 3 to 6 months in episodic migraine and 6 to 12 months in chronic migraine. Education about not overusing acute medications is also essential for all patients with migraine. Key words: migraine, preventive treatment, evidence-based medicine, guidelines, CGRP monoclonal antibodies, onabotulinumtoxinA, neuromodulation.

Nutraceuticals and migraine: further strategy for the treatment of specific conditions.

Nutraceuticals might be defined as food or dietary supplements that provide medicinal or health benefits. Current preventive treatment of migraine includes nutraceuticals as well as conventional drugs. These non-pharmacological therapies, such as magnesium, coenzyme Q10, feverfew, riboflavin, and phycocyanins, are particularly useful in certain categories of patients (adolescents, pregnant or breastfeeding women, the elderly with complex drug therapy, the patient with contraindication to the usual pharmacological therapies) when a conventional drug therapy cannot be prescribed or may be not well tolerated. The evidence currently available confirms a modest efficacy but a very good safety and tolerability profile.

A Digital Therapeutic Allowing a Personalized Low-Glycemic Nutrition for the Prophylaxis of Migraine: Real World Data from Two Prospective Studies.

Migraine is a headache disorder associated with a high socioeconomic burden. The digital therapeutic sinCephalea provides an individualized low-glycemic diet based on continuous glucose measurement and is intended to provide a non-pharmacological migraine prophylaxis. We performed two prospective studies with migraine patients who used sinCephalea over a period of 16 weeks. The patients used a headache diary and recorded their migraine-related daily life impairments using the assessment tools HIT-6 and MIDAS for a pre versus post comparison. In addition, continuous glucose data of patients were compared to healthy controls. In both studies, patients reported a reduction of headache and migraine days as well as reductions in HIT-6 and MIDAS scores. More specifically, migraine days decreased by 2.40 days (95% CI [-3.37; -1.42]), HIT-6 improved by 3.17 points (95% CI [-4.63; -1.70]) and MIDAS by 13.45 points (95% CI [-22.01; -4.89]). Glucose data suggest that migraine patients have slightly increased mean glucose values compared to healthy controls, but drop into a glucose range that is below one's individual standard range before a migraine attack. In conclusion, sinCephalea is a non-pharmacological, digital migraine prophylaxis that induces a therapeutic effect within the range of pharmacological interventions.

Effects of aerobic exercise and progressive muscle relaxation on migraine.

OBJECTIVE: To determine the effect of aerobic exercises and progressive muscle relaxation in migraine patients. METHODS: The quasi-experimental study was conducted at the Sheikh Khalifa Bin Zayed Al Nayhan Hospital / Combined Military Hospital, Muzaffarabad, Azad Jammu and Kashmir, from February to July 2017, and comprised migraine patients of either gender aged 20-50 years. They were divided into experimental and control group. Experimental group A received supervised exercises protocol, including aerobic exercise (stationary bicycle) 30min with 10min warm-up and 5min cool-down followed by progressive muscle relaxation for 15min 3 times a week for 6 weeks along with prophylactic medicine. The control group received prophylactic medicines flunarazine 5mg twice daily, inderal 10mg thrice daily and nortriptyline 25mg at night. Patients were assessed using Numeric Pain Rating Scale, Migraine Disability Assessment Scale, Headache Disability Index, Headache Impact test-6 and the Central Sensitisation Inventory at baseline, midline and at the completion of intervention. Data was analysed using SPSS 21. RESULTS: Of the 28 patients, there were 14(50%) in each of the two groups. Overall, there were 24(85.7%) females and 4(14.3%) males with a mean age of 29.7±10 years. There were significant improvements in all parameters in both the groups, but group A had significantly better outcome post-intervention (p<0.05). CONCLUSIONS: Prophylactic medicine, aerobic exercises and progressive muscle relaxation, when used together, were found to be effective means of intervention for migraine.

The Impact of Vitamin D3 Supplementation to Topiramate Therapy on Pediatric Migraine Prophylaxis.

Background:There is still a need for more studies to evaluate the role of vitamin D3 in pediatric migraine prophylaxis. Objectives: We aimed to evaluate the effects and safety of vitamin D3 supplementation to topiramate on pediatric migraine. Methods: A double-blinded prospective clinical trial was conducted on 5- to 14-year-old children with migraine. They were randomly assigned in a 1:1 ratio into 2 groups, one with vitamin D3 supplementation (the supplementation group) and the other without vitamin D supplementation (the placebo group). The supplementation group received topiramate plus one 5000-IU dose of vitamin D3 daily for 4 months. The placebo group received topiramate with a placebo capsule without any effective substances. The primary outcomes were a monthly frequency of headache attacks, a good response to intervention, and reduction in migraine severity, duration, and disability before and after treatment. Fifty-six children completed the trial. Vitamin D3 supplementation to topiramate was more effective than the placebo group in the reduction of monthly frequency (6231.31 vs 9792.24 times, P = .01) and disability score for migraines (17 566.43 vs 25 187.65, P = .04). A good response was observed in 76.13% of patients in the vitamin D3 supplementation group and 53.5% of patients in the placebo group, and vitamin D3 supplementation was significantly more effective than placebo (P = .01). Side effects were observed in 13.3% and 20% of the intervention group and placebo groups, respectively, P = .5. Conclusion: Vitamin D3 supplementation in pediatric migraine prophylaxis could be a well-tolerated, safe, and effective strategy.