Efficacy of various exercise interventions for migraine treatment: A systematic review and network meta-analysis.

OBJECTIVE: To compare various exercise modalities' efficacy on migraine frequency, intensity, duration, and disability. BACKGROUND: Exercise has been shown to be an effective intervention to reduce migraine symptoms and disability; however, no clear evidence exists regarding the most effective exercise modalities for migraine treatment. METHODS: A systematic review was performed in PubMed, PEDro, Web of Science, and Google Scholar. Clinical trials that analyzed the efficacy of various exercise modalities in addressing the frequency, intensity, duration, and disability of patients with migraine were included. Eight network meta-analyses based on frequentist (F) and Bayesian (B) models were developed to estimate the direct and indirect evidence of various exercise modalities. Standardized mean difference (SMD) and 95% confidence (CI) and credible intervals (CrI) were calculated for each treatment effect based on Hedge's g and p scores to rank the modalities. RESULTS: We included 28 studies with 1501 migraine participants. Yoga (F: SMD -1.30; 95% CI -2.09, -0.51; B: SMD -1.33; 95% CrI -2.21, -0.45), high-intensity aerobic exercise (F: SMD -1.30; 95% CI -2.21, -0.39; B: SMD -1.17; 95% CrI -2.20, -0.20) and moderate-intensity continuous aerobic exercise (F: SMD -1.01; 95% CI -1.63, -0.39; B: SMD -1.06; 95% CrI -1.74, -0.38) were significantly superior to pharmacological treatment alone for decreasing migraine frequency based on both models. Only yoga (F: SMD -1.40; 95% CI -2.41, -0.39; B: SMD -1.41; 95% CrI -2.54, -0.27) was significantly superior to pharmacological treatment alone for reducing migraine intensity. For diminishing migraine duration, high-intensity aerobic exercise (F: SMD -1.64; 95% CI -2.43, -0.85; B: SMD -1.56; 95% CrI -2.59, -0.63) and moderate-intensity continuous aerobic exercise (SMD -0.96; 95% CI -1.50, -0.41; B: SMD -1.00; 95% CrI -1.71, -0.31) were superior to pharmacological treatment alone. CONCLUSION: Very low-quality evidence showed that yoga, high- and moderate-intensity aerobic exercises were the best interventions for reducing migraine frequency and intensity; high- and moderate-intensity aerobic exercises were best for decreasing migraine duration; and moderate-intensity aerobic exercise was best for diminishing disability.

Prescription of therapeutic exercise in migraine, an evidence-based clinical practice guideline.

The main objective of this clinical practice guideline is to provide a series of recommendations for healthcare and exercise professionals, such as neurologists, physical therapists, and exercise physiologists, regarding exercise prescription for patients with migraine.This guideline was developed following the methodology and procedures recommended in the Appraisal of Guidelines for Research and Evaluation (AGREE). The quality of evidence and strength of recommendations were evaluated with the Scottish Intercollegiate Guidelines Network (SIGN). A systematic literature review was performed and an established appraisal process was employed to rate the quality of relevant scientific research (Grading of Recommendations Assessment, Development, and Evaluation methodology).The evaluation of the current evidence, the elaboration of the grades of recommendation, and their validation show a B grade of recommendation for aerobic exercise, moderate-continuous aerobic exercise, yoga, and exercise and lifestyle recommendations for the improvement of symptoms, disability, and quality of life in patients with migraine. Relaxation techniques, high-intensity interval training, low-intensity continuous aerobic exercise, exercise and relaxation techniques, Tai Chi, and resistance exercise obtained a C grade of recommendation for the improvement of migraine symptoms and disability.

Effectiveness of anti-CGRP monoclonal antibodies on central symptoms of migraine.

BACKGROUND: Clinical trials and observational studies with anti-calcitonin gene-related peptide antibodies poorly investigated their impact on migraine prodromal and accompanying symptoms. This information might help deciphering the biologics' pharmacodynamic and provide hints on migraine pathogenesis. Herein, we report the effects of erenumab, fremanezumab and galcanezumab on attack prodromal and accompanying symptoms and on neurological and psychiatric traits. . METHODS: An explorative, prospective, questionnaire-based study was completed by a cohort (n = 80) of patients with chronic migraine patients presenting a sustained reduction of ≥50% of Migraine Disability Assessment Score and ≥30% of monthly migraine days three months after anti-calcitonin gene-related peptide antibodies treatment. RESULTS: The majority of patients experienced a complete prevention of migraine symptoms without evidence of initial onset followed by attack abortion. Few patients reported the recurrence of prodromal (from 10% to 12.5%) or accompanying (from 1.3% to 8.8%) symptoms without headache. All patients with migraine with aura reported a decrease of aura incidence. Sleep changes (51.2%), increase in appetite (20.0%) and weight (18.8%) as well as a reduction in stress (45.0%), anxiety (26.3%), and panic attacks (15%) were also reported. CONCLUSION: Anti-calcitonin gene-related peptide antibodies seems to significantly impact brain functions of migraineurs, preventing not only migraine headache but also its anticipatory and accompanying symptoms.

Age-related features in vestibular migraine onset: A multiparametric analysis.

BACKGROUND: Clinical heterogeneity is a peculiarity of vestibular migraine, in contrast to other vestibular disorders that have a more stereotypical expression. Migraine presents a range of variability in symptoms depending on the age of the patient. Supposing that migraine headache and vestibular migraine share the same pathogenetic mechanisms, a multiparametric analysis was performed to verify the hypotheses of an age-related influence on the clinical features of vestibular migraine at the onset. METHODS: In this retrospective study, we analysed the clinical records of 72 consecutive patients affected by vestibular migraine from June 2012 to November 2018: 64 females and eight males; mean age 38.2 ± 9.6. We considered only patients that reported onset of vestibular symptoms within 12 months preceding inclusion into the study. RESULTS: Statistical analysis shows a significant increase in the diagnosis of probable vestibular migraine with increasing age and a decrease in vestibular migraine diagnosis (p = 0.034). The incidence of spontaneous dizziness increases with age (p = 0.012); by contrast, external spontaneous vertigo, and visually induced vertigo decrease after 40 years of age (p = 0.018), clinically characterising the onset of juvenile forms. Spontaneous vertigo, head motion-induced vertigo/dizziness, and positional vertigo did not show significant variations with age. CONCLUSION: Our data show that the type of vestibular symptoms in vestibular migraine varies according to the age of onset.

The effects of concurrent Coenzyme Q10, L-carnitine supplementation in migraine prophylaxis: A randomized, placebo-controlled, double-blind trial.

PURPOSE: The present study aimed to determine the effects of combined supplementation of Coenzyme Q10 with L-carnitine on mitochondrial metabolic disorders marker and migraine symptoms among migraine patients. METHODS: A total of 56 men and women, between 20-40 years of age with migraine headache, participated in this randomized, double-blind, placebo-controlled, parallel study. The subjects were randomly assigned to receive either 30 mg/day Coenzyme Q10 and 500 mg/day L-carnitine at the same time and/or placebo tablets for 8 weeks. The measurements were completed at the beginning and end of the study. The primary outcome was severity of headache attacks. The secondary outcomes included duration, frequency of headache attacks, the headache diary results (HDR), and serum levels of lactate. RESULTS: A significant reduction was obtained in serum levels of lactate (-2.28 mg/dl, 95% CI: -3.65, -0.90; p = 0.002), severity (-3.03, 95% CI: -3.65, -2.40; p ≤ 0.001), duration (-7.67, 95% CI: -11.47, -3.90; p ≤ 0.001), frequency (-5.42, 95% CI: -7.31, -3.53; p ≤ 0.001) and HDR (-103.03, 95% CI: -145.76, -60.29; p ≤ 0.001) after 8 weeks. CONCLUSION: This double-blind parallel study provides evidences supporting the beneficial effects of Coenzyme Q10 and L-carnitine supplements on serum levels of lactate and migraine symptoms. TRIAL REGISTRATION: IRCT20121216011763N21.

Exploring the symptoms and sleep disorders associated with migraines in women of Syria: A cross-sectional observational study.

Background and Aim: Migraine is a prevalent neurological disorder characterized by recurring episodes of debilitating headache accompanied by associated symptoms and sleep disorders. This study aims to investigate migraine-associated symptoms in female migraineurs within the Syrian population and the relation between migraines and sleep issues. Methods: A questionnaire-based cross-sectional observational study was conducted among the Syrian population. A total of 1009 women were enrolled in this study, including women without a history of migraine (Control group) and migraineurs (Case group) who had received a diagnosis of migraine from a hospital or private clinic. Data about migraine-related symptoms, including tingling, visual disturbances, Nausea/Vomiting, and epileptic seizures as well as sleep-related symptoms such as interrupted sleep, frequent awakenings, insomnia, snoring, and narcolepsy were gathered. Chi-square test was used to examine the relation between migraines and sleep issues. Results: A total of 1009 women were enrolled in this study including 531 migraineurs and 478 healthy women. The study revealed that the most commonly experienced symptoms during migraine attacks were nausea/vomiting and visual disturbances, followed by tingling. Total Unduplicated Reach and Frequency analysis showed that visual disturbances and nausea/vomiting were the two most frequent symptoms that co-occurred during migraine attacks. The study also demonstrated a significant relationship between snoring, insomnia, and narcolepsy with migraine (p = 0.038), with these sleep disorders being more prevalent among migraineurs. Conclusion: The findings indicate a significant association between migraines and sleep disorders, with migraineurs being at a significantly higher risk of experiencing poor sleep quality compared to healthy women. Addressing sleep disorders is crucial in managing patients with migraines. This study is the first of its kind in the Syrian population, providing valuable insights into the symptoms and sleep disorders associated with migraines in this population.

Acute Treatment Patterns, Migraine Burden, and Healthcare Resource Use in People With Migraine: Results From the OVERCOME (EU) Observational Study.

INTRODUCTION: The ObserVational survey of the Epidemiology, tReatment and Care Of MigrainE (OVERCOME) European Union (EU) is part of an overarching population-based study program that also includes the United States and Japan. Here, we report data on the migraine/severe headache burden and the use of acute medication and healthcare resources in Spain and Germany. METHODS: OVERCOME (EU) was an online, non-interventional, cross-sectional survey conducted in adults in Spain and Germany between October 2020 and February 2021. A total migraine cohort was established based on health survey participants who reported headache/migraine in the last 12 months AND identified as having migraine based on modified International Classification of Headache Disorders, third edition criteria OR self-reported physician diagnosis. Data were analyzed for the total migraine cohort and the subcohort with moderate to severe headache attacks, with average pain severity ≥ 5 points, pain duration ≥ 4 h, and at least moderate disability due to migraine [Migraine Disability Assessment (MIDAS) score ≥ 11] over the past 3 months. RESULTS: Pain of moderate or severe intensity was the most frequent symptom in the total migraine cohort (n = 19,103/20,756; 92.0%). Proportions of participants reporting severe disability (MIDAS Grade IV), poorer quality of life (QoL; Migraine-Specific QoL Questionnaire), and higher interictal burden (Migraine Interictal Burden Scale-4), generally increased with number of headache days (HDs)/month. Most participants (92.5%) reported current acute migraine/severe headache medication use, although only 39.0% were using triptans. In the moderate to severe attacks subcohort (n = 5547), 48.4% were using triptans, with nonsteroidal anti-inflammatory drugs the most common acute medication. The moderate to severe attacks subcohort also reported poorer QoL and greater pain and disability with increasing HDs/month, although severe interictal burden was reported for ~ 60% of participants regardless of HDs/month. Treatment satisfaction (six-item migraine Treatment Optimization Questionnaire) in those using triptans was generally poor in both total and subcohorts. CONCLUSION: High migraine-related burden levels were reported, despite use of acute medication. Although triptans are recommended for moderate to severe migraine attacks in Spanish and German guidelines, less than half of participants were using triptans; treatment satisfaction in those using triptans was generally poor. New tailored treatment options may help address unmet needs in current acute treatment.

Semi-Automated Recording of Facial Sensitivity in Rat Demonstrates Antinociceptive Effects of the Anti-CGRP Antibody Fremanezumab.

Migraine pain is frequently accompanied by cranial hyperalgesia and allodynia. Calcitonin gene-related peptide (CGRP) is implicated in migraine pathophysiology but its role in facial hypersensitivity is not entirely clear. In this study, we investigated if the anti-CGRP monoclonal antibody fremanezumab, which is therapeutically used in chronic and episodic migraines, can modify facial sensitivity recorded by a semi-automatic system. Rats of both sexes primed to drink from a sweet source had to pass a noxious mechanical or heat barrier to reach the source. Under these experimental conditions, animals of all groups tended to drink longer and more when they had received a subcutaneous injection of 30 mg/kg fremanezumab compared to control animals injected with an isotype control antibody 12-13 days prior to testing, but this was significant only for females. In conclusion, anti-CGRP antibody, fremanezumab, reduces facial sensitivity to noxious mechanical and thermal stimulation for more than one week, especially in female rats. Anti-CGRP antibodies may reduce not only headache but also cranial sensitivity in migraineurs.

Galcanezumab Effects on Migraine Severity and Symptoms in Japanese Patients with Episodic Migraine: Secondary Analysis of a Phase 2 Randomized Trial.

INTRODUCTION: Galcanezumab, a humanized monoclonal antibody against calcitonin gene-related peptide, is a preventive migraine treatment. In global, randomized, placebo-controlled trials, galcanezumab reduced migraine headache severity and the frequency of migraine headaches associated with nausea and/or vomiting, photophobia and phonophobia, prodromal symptoms, or aura. We report secondary analyses from a Japanese phase 2 trial that assessed the effect of galcanezumab on migraine headache severity, frequency of migraine-associated symptoms, and frequency of migraine headaches during menstrual periods in Japanese patients with episodic migraine. METHODS: Adults with migraine (International Classification of Headache Disorders, 3rd edition; 4-14 migraine headache days/month) were randomized (2:1:1) to a monthly placebo (n = 230), 120 mg galcanezumab (240 mg loading dose; n = 115), or 240 mg galcanezumab (n = 114) for 6 months (double-blind). Patients recorded migraine headache days, severity, and symptoms in an electronic diary. Changes from baseline were analyzed (mixed model for repeated measures). RESULTS: Both galcanezumab doses significantly reduced the number of monthly moderate-to-severe and severe migraine headache days compared with placebo, overall (difference in least-squares mean change from baseline, 120 mg/240 mg versus placebo: moderate-to-severe, -1.9/-1.8 days; severe: -0.4/-0.4 days) and in each month; mean severity score was significantly reduced in the 240 mg group. Both galcanezumab doses significantly reduced the number of migraine headache days with nausea/vomiting (-1.1/-1.0 days), photophobia/phonophobia (-2.3/-1.7 days), prodromal symptoms (-0.7/-0.8 days), and aura (-0.7/-0.7 days). In most cases, the proportion of migraine headache days with these symptoms was reduced by galcanezumab. Both galcanezumab doses reduced the number of migraine headache days occurring during menstrual periods (n = 269; -0.8/-0.9 days). CONCLUSION: Once-monthly galcanezumab significantly reduced the frequency of migraine headache days with moderate-to-severe or severe headache, migraine headache days with migraine-associated symptoms, and migraine headache days during menstrual periods in Japanese patients with episodic migraine, consistent with results from global studies. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02959177).