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A systematic literature review of observational studies of the bidirectional association between metabolic syndrome and migraine.
Andreeva, VA, Galan, P, Julia, C, Fezeu, L, Hercberg, S, Kesse-Guyot, E
Diabetes & metabolism. 2019;(1):11-18
Abstract
AIMS: To evaluate all epidemiological evidence in the literature linking the metabolic syndrome (MetS) and migraine in adults. METHODS Database (Medline, Embase; published reports up to November 2017) and manual searches were performed. Information on data collection, sample characteristics, study design, MetS and migraine assessment, and results was extracted from each relevant publication. The methodological quality of each study was also assessed. RESULTS A total of 15 observational epidemiological studies in adults, published between 2009 and 2017, were retrieved. Of these, one employed a prospective design, while the rest had a cross-sectional (13 studies) or case-control (one study) design. Five studies assessed the presence of migraine in individuals with MetS, whereas 10 studies assessed the presence or risk of MetS in migraineurs. Most participants were female hospital outpatients. The sole prospective cohort study reported 11-year MetS incidence of 21.8% in migraineurs with aura, 16.8% in migraineurs without aura and 14.5% in subjects without headaches. Most studies (60%) provided no statistical estimates of association. Methodological flaws included selection biases, lack of power analysis, unsuitable research plans and no multivariable analyses. Meta-analysis was not feasible with the available data. CONCLUSION Our systematic review has identified major gaps in knowledge and weaknesses in research that should provide an impetus for future epidemiological investigations using more rigorous methodology, large general-population prospective cohorts, and substantial data on dietary behaviours and lifestyle.
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Complementary and Integrative Health Treatments for Migraine.
Patel, PS, Minen, MT
Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society. 2019;(3):360-369
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Abstract
BACKGROUND Migraine is a chronic disabling neurologic condition that can be treated with a combination of both pharmacologic and complementary and integrative health options. EVIDENCE ACQUISITION With the growing interest in the US population in the use of nonpharmacologic treatments, we reviewed the evidence for supplements and behavioral interventions used for migraine prevention. RESULTS Supplements reviewed included vitamins, minerals, and certain herbal preparations. Behavioral interventions reviewed included cognitive behavioral therapy, biofeedback, relaxation, the third-wave therapies, acupuncture, hypnosis, and aerobic exercise. CONCLUSIONS This article should provide an appreciation for the wide range of nonpharmacologic therapies that might be offered to patients in place of or in addition to migraine-preventive medications.
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Vitamin D in migraine headache: a comprehensive review on literature.
Ghorbani, Z, Togha, M, Rafiee, P, Ahmadi, ZS, Rasekh Magham, R, Haghighi, S, Razeghi Jahromi, S, Mahmoudi, M
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2019;(12):2459-2477
Abstract
INTRODUCTION As a primary headache, migraine has been established as the first leading disability cause worldwide in the subjects who aged less than 50 years. A variety of dietary supplements have been introduced for migraine complementary treatment. As an anti-inflammatory and antioxidant agent, vitamin D is one of these agents which has been of interest in recent years. Although higher prevalence of vitamin D deficiency/insufficiency has been highlighted among migraineurs compared to controls, there is not any consensus in prescribing vitamin D in clinical practice. Therefore, in the current review, in addition to observational and case-control studies, we also included clinical trials concerning the effects of vitamin D supplementation on migraine/headache. METHODS Based on a PubMed/MEDLINE and ScienceDirect database search, this review study includes published articles up to June 2019 concerning the association between migraine/headache and vitamin D status or supplementation. RESULTS The percentage of subjects with vitamin D deficiency and insufficiency among migraineurs and headache patients has been reported to vary between 45 and 100%. In a number of studies, vitamin D level was negatively correlated with frequency of headaches. The present findings show that supplementation with this vitamin in a dose of 1000-4000 IU/d could reduce the frequency of attacks in migraineurs. CONCLUSION It seems a high proportion of migraine patients might suffer from vitamin D deficiency/insufficiency. Further, the current evidence shows that in addition to routine drug therapy, vitamin D administration might reduce the frequency of attacks in migraineurs. However, these results have yet to be confirmed.
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Pharmacotherapy for acute migraines in children and adolescents.
Barbanti, P, Grazzi, L, Egeo, G
Expert opinion on pharmacotherapy. 2019;(4):455-463
Abstract
INTRODUCTION Migraine is increasingly recognized as an extremely burdensome and disabling disorder in both children and adolescents. A proper treatment plan is needed to improve the quality of life of both children and families as well as to minimize the risk of disease progression. AREAS COVERED This review focuses on the current pharmacotherapy for acute migraine in pediatric populations, taking into account specific considerations for those drugs tested in randomized, placebo-controlled trials (RCTs). EXPERT OPINION A large number of RCTs have documented the efficacy, tolerability, and safety of different compounds. Triptans appears more effective than placebo but results are variable and inconsistent. Almotriptan and rizatriptan are effective as oral formulations, as well as sumatriptan and zolmitriptan as both oral and nasal spray formulations. Adding non-steroidal anti-inflammatory drugs (NSAIDs) reinforces triptan's effectiveness. Furthermore, small RCTs have documented both the efficacy of ibuprofen and the ineffectiveness of acetaminophen. Naproxen, ketoprofen, diclofenac, and indomethacin - NSAIDs effective in acute migraines in adults - should be tested also in pediatric subjects. Furthermore, the authors suggest that dopamine receptor antagonists should be considered in cases of severe migraines. Lastly, better designed RCTs are needed to fine-tune current therapeutic resources.
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Association of diet and headache.
Razeghi Jahromi, S, Ghorbani, Z, Martelletti, P, Lampl, C, Togha, M, ,
The journal of headache and pain. 2019;(1):106
Abstract
The global prevalence of migraine as a primary headache has been estimated as 14.4% in both sexes. Migraine headache has been ranked as the highest contributor to disability in under 50 years old population in the world. Extensive research has been conducted in order to clarify the pathological mechanisms of migraine. Although uncertainties remains, it has been indicated that vascular dysfunction, cortical spreading depression (CSD), activation of the trigeminovascular pathway, pro-inflammatory and oxidative state may play a putative role in migraine pain generation. Knowledge about pathophysiological mechanisms of migraine should be integrated into a multimodal treatment approach to increase quality of life in patients. With respect to this, within the integrative health studies growing interest pertains to dietary interventions. Although the number of studies concerning effects of diet on headache/migraine is not yet very large, the current article will review the available evidence in this area. All publications on headache/migraine and dietary interventions up to May 2019 were included in the present review through a PubMed/MEDLINE and ScienceDirect database search. According to the current findings, Ketogenic diet and modified Atkins diet are thought to play a role in neuroprotection, improving mitochondrial function and energy metabolism, compensating serotoninergic dysfunction, decreasing calcitonin gene-related peptide (CGRP) level and suppressing neuro-inflammation. It can also be speculated that prescription of low glycemic diet may be promising in headache/migraine control through attenuating the inflammatory state. Moreover, obesity and headaches including migraine could be attributed to each other through mechanisms like inflammation, and irregular hypothalamic function. Thereby, applying dietary strategies for weight loss may also ameliorate headache/migraine. Another important dietary intervention that might be effective in headache/migraine improvement is related to balance between the intake of essential fatty acids, omega-6 and omega-3 which also affect inflammatory responses, platelet function and regulation of vascular tone. Regarding elimination diets, it appears that targeted these diets in migraine patients with food sensitivities could be effective in headache/migraine prevention. Taken together, dietary approaches that could be considered as effective strategies in headache/migraine prophylaxis include weight loss diets in obese headache patients, ketogenic and low-calorie diets, reducing omega-6 and increasing omega-3 fatty acid intakes.
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Diamine oxidase (DAO) supplement reduces headache in episodic migraine patients with DAO deficiency: A randomized double-blind trial.
Izquierdo-Casas, J, Comas-Basté, O, Latorre-Moratalla, ML, Lorente-Gascón, M, Duelo, A, Soler-Singla, L, Vidal-Carou, MC
Clinical nutrition (Edinburgh, Scotland). 2019;(1):152-158
Abstract
BACKGROUND & AIMS Histamine intolerance is a disorder in the homeostasis of histamine due to a reduced intestinal degradation of this amine, mainly caused by a deficiency in the enzyme diamine oxidase (DAO). Among histamine related symptoms, headache is one of the most recorded. Current clinical strategies for the treatment of the symptomatology related to this disorder are based on the exclusion of foods with histamine or other bioactive amines and/or exogenous DAO supplementation. The aim of this study was to assess the efficacy of a food supplement consisting of DAO enzyme as a preventive treatment of migraine in patients with DAO deficiency through a randomized double-blind trial. METHODS 100 patients with confirmed episodic migraine according to current International Headache Society (IHS) criteria and DAO deficiency (levels below 80 HDU/ml) were randomized in two groups. One group received DAO enzyme supplementation and the other received placebo for one month. Clinical outcomes assessed were duration and number of attacks, perception of pain intensity and adverse effects during treatment. The use of triptans was also recorded. RESULTS Great variability was found in the duration of migraine attacks reported by placebo and DAO groups. A significant reduction (p = 0.0217) in hours of pain was achieved in patients treated with DAO supplement, with mean durations of 6.14 (±3.06) and 4.76 (±2.68) hours before and after treatment, respectively. A smaller reduction without statistical signification was also observed for this outcome in the placebo group, from 7.53 (±4.24) to 6.68 (±4.42) hours. Only in DAO group, a decrease in the percentage of patients taking triptans was observed. The number of attacks and the scores of pain intensity showed a similar reduction in both groups. No adverse effects were registered in patients treated with DAO enzyme. CONCLUSIONS Migrainous patients supplemented with DAO enzyme during one month significantly reduced the duration of their migraine attacks by 1.4 h. No statistically significant reduction was found in placebo group before and after treatment. The reduction of pain hours observed in placebo group (0.9 h) could explain the lack of significant differences between both study groups. One month of DAO supplementation has demonstrated a positive trend in the improvement of migraine but more studies with a longer treatment period are needed to better assess the efficacy of DAO supplementation. CLINICAL TRIAL REGISTRATION NUMBER ISRCTN10091019; www.isrctn.org.
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Large-scale plasma metabolome analysis reveals alterations in HDL metabolism in migraine.
Onderwater, GLJ, Ligthart, L, Bot, M, Demirkan, A, Fu, J, van der Kallen, CJH, Vijfhuizen, LS, Pool, R, Liu, J, Vanmolkot, FHM, et al
Neurology. 2019;(16):e1899-e1911
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Abstract
OBJECTIVE To identify a plasma metabolomic biomarker signature for migraine. METHODS Plasma samples from 8 Dutch cohorts (n = 10,153: 2,800 migraine patients and 7,353 controls) were profiled on a 1H-NMR-based metabolomics platform, to quantify 146 individual metabolites (e.g., lipids, fatty acids, and lipoproteins) and 79 metabolite ratios. Metabolite measures associated with migraine were obtained after single-metabolite logistic regression combined with a random-effects meta-analysis performed in a nonstratified and sex-stratified manner. Next, a global test analysis was performed to identify sets of related metabolites associated with migraine. The Holm procedure was applied to control the family-wise error rate at 5% in single-metabolite and global test analyses. RESULTS Decreases in the level of apolipoprotein A1 (β -0.10; 95% confidence interval [CI] -0.16, -0.05; adjusted p = 0.029) and free cholesterol to total lipid ratio present in small high-density lipoprotein subspecies (HDL) (β -0.10; 95% CI -0.15, -0.05; adjusted p = 0.029) were associated with migraine status. In addition, only in male participants, a decreased level of omega-3 fatty acids (β -0.24; 95% CI -0.36, -0.12; adjusted p = 0.033) was associated with migraine. Global test analysis further supported that HDL traits (but not other lipoproteins) were associated with migraine status. CONCLUSIONS Metabolic profiling of plasma yielded alterations in HDL metabolism in migraine patients and decreased omega-3 fatty acids only in male migraineurs.
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The effects of a multispecies probiotic supplement on inflammatory markers and episodic and chronic migraine characteristics: A randomized double-blind controlled trial.
Martami, F, Togha, M, Seifishahpar, M, Ghorbani, Z, Ansari, H, Karimi, T, Jahromi, SR
Cephalalgia : an international journal of headache. 2019;(7):841-853
Abstract
BACKGROUND The current study was designed to assess the effect of supplementation with a 14-strain probiotic mixture on episodic and chronic migraine characteristics. METHODS Forty episodic and 39 chronic migraine patients who completed this randomized double-blind controlled trial received two capsules of multispecies probiotic or placebo. The migraine severity was assessed by visual analog scale (VAS). The number of abortive drugs consumed, migraine days, frequency and duration of attacks were recorded on paper-based headache diaries. Serum tumor necrosis factor alpha (TNF-α) and C- reactive protein (CRP) levels were measured at baseline and the end of the intervention. RESULTS After a 10-week intervention, among episodic migraineurs the mean frequency of migraine attacks significantly reduced in the probiotic group compare to the placebo group (mean change: -2.64 vs. 0.06; respectively, p < 0.001). A significant reduction was also evident in the migraine severity (mean decrease: -2.14 in the probiotic group and 0.11 in the placebo group; p < 0.001). Episodic migraineurs who received the probiotic also showed significant reduction in abortive drug usage per week (mean change: -0.72; p < 0.001) compare to baseline, while there was no significant changes within the placebo group. In chronic migraine patients, after an 8-week intervention, the mean frequency of migraine attacks significantly reduced in the probiotic compared to the placebo group (mean change: -9.67 vs. -0.22; p ≤ 0.001). In contrast to the placebo, probiotic supplementation significantly decreased the severity (mean changes: -2.69; p ≤ 0.001), duration (mean changes: -0.59; p ≤ 0.034) of attacks and the number of abortive drugs taken per day (mean changes: -1.02; p < 0.001), in chronic migraine patients. We failed to detect any significant differences in the serum levels of inflammatory markers at the end of the study either in chronic or in episodic migraineurs. DISCUSSION The results of this study showed that the 14-strain probiotic mixture could be an effective and beneficial supplement to improve migraine headache in both chronic and episodic migraineurs. Further research is required to confirm our observations.
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Experiences of an outpatient infusion center with intravenous magnesium therapy for status migrainosus.
Xu, F, Arakelyan, A, Spitzberg, A, Green, L, Cesar, PH, Csere, A, Nworie, O, Sahai-Srivastava, S
Clinical neurology and neurosurgery. 2019;:31-35
Abstract
OBJECTIVES Exploratory study to investigate the effectiveness of intravenous magnesium as an abortive for status migrainosus in an outpatient infusion center, and characterize the patients who benefit from the therapy. PATIENTS & METHODS Retrospective analysis of 234 migraine patients who received IV magnesium as a headache abortive, at the headache clinic of University of Southern California. Additional intramuscular (IM) injections for nausea (prochlorperazine, odansetron, metoclopramide) or for refractory pain (ketorolac, dexamethasone, sumatriptan, dihydroergotamine), were administered as necessary. Immediately before and after treatment, self-reported pain levels were recorded using an 11-point numeric pain rating scale (0-10). RESULTS Our patient sample has a mean age of 44 years and was predominantly female (79%). 36 (19%) had migraine with aura. Overall, pain score decreased from 5.46±2.39 to 3.56 ± 2.75 (P < 0.001) after magnesium infusion. One hundred twenty-seven (54%) patients had clinically significant pain reduction, as defined by pain decrease ≥ 30%. One hundred and four patients (44%) received IV magnesium and did not require additional intramuscular (IM) medications for pain. In patients who did not receive additional IM medications for pain, pain score decreased from 4.76 ± 2.41 to 2.95 ± 2.70 (p < 0.001), and 61 out of 104 (59%) experienced ≥ 30% pain reduction. Patients with less severe pain tended to have a better response than patients with more severe pain, as patients with ≥30% pain reduction had a significantly lower pre-treatment pain score (p = 0.018). CONCLUSION For a subset of patients with status migrainosus, IV magnesium therapy results in clinically significant pain relief without the need for intramuscular pain medications. Therefore, IV magnesium may be useful as a cost-effective first-line parental therapy for status migrainosus, especially for patients who initially present with lower pain intensity.
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Navigating monoclonal antibody use in breastfeeding women: Do no harm or do little good?
LaHue, SC, Gelfand, AA, Bove, RM
Neurology. 2019;(15):668-672
Abstract
Many neurologic diseases disproportionately affect women, particularly during their reproductive years. For many of these diseases, monoclonal antibodies (mAbs) are becoming widely available as a treatment option, for example, in migraine, multiple sclerosis, and myasthenia gravis. Yet, despite how common pregnancy is (latest estimates suggest that 86% of US women ages 40-44 have given birth), there is a paucity of research on the safety of prescription medications, including mAbs, during the peripartum period. In this article, we focus on the safety of mAbs during breastfeeding. We summarize how pregnancy affects the trajectory of these diseases and explore the benefit derived from mAb therapies. We posit that as neurologists, we are uniquely poised to lead the study of peripartum safety for the mAbs now on the market and provide a framework for their future study.