Migraine management: Non-pharmacological points for patients and health care professionals.

Migraine is a highly prevalent disorder with an enormous burden on societies. Different types of medications are used for controlling both acute attacks and prevention. This article reviews some non-pharmacological recommendations aiming to manage migraine disorder better and prevent headache attacks. Different triggers of migraine headache attacks, including environmental factors, sleep pattern changes, diet, physical activity, stress and anxiety, some medications, and hormonal changes, are discussed. It is advised that they be identified and managed. Patients should learn the skills to cope with the trigger factors that are difficult to avoid. In addition, weight control, management of migraine comorbidities, lifestyle modification, behavioural treatment and biofeedback, patient education, using headache diaries, and improving patients' knowledge about the disease are recommended to be parts of migraine management. In addition, using neuromodulation techniques, dietary supplements such as riboflavin, coenzyme Q10 and magnesium, and acupuncture can be helpful. Non-pharmacological approaches should be considered in migraine management. Furthermore, the combination of pharmacological and non-pharmacological approaches is more effective than using each separately.

Review on Headache Related to Dietary Supplements.

PURPOSE OF REVIEW: The lifetime prevalence of headaches is 96%. Approximately 11% of the adult population worldwide has a migraine headache. Migraine is a complex disorder that is more than a simple headache. So far, many underlying mechanisms, i.e. inflammatory, vascular, neurogenic have been hypothesized. In recent years evidences proposed that an energy deficit due to changes in mitochondrial function contributes to migraine pathophysiology as an upstream disorder. Recent insights suggested that the coexistence of sensory-stimuli surplus and energy-reserve shortage activate the trigeminovascular system. Some nutrients are considered as essential elements in mitochondrial bioenergetics and some others are known as natural immuno-modulatory components. Also, evidence showed their beneficial effect in headache prophylaxis and treatment. In present study, we aimed to review the available data in this field. RECENT FINDINGS: Vitamin B group, magnesium, and Coenzyme Q10 (CoQ10) are well-known for their function in mitochondrial energy metabolism. On the other hand, studies support their beneficial role in controlling migraine headache symptoms. For instance, daily intake of 400-milligram riboflavin for 3 months resulted in more than 50% reduction in migraine attacks in more than half of the consumers. According to recent evidence, vitamin D and Omega-3 which are considered as famous immune-modulatory compounds are also reported to be effective in migraine prophylaxis. For example, every 22% reduction in migraine headache occurrence was reported for every 5 ng/ml rise in serum vitamin D. Supplementation with vitamin B group, CoQ10, magnesium, vitamin D and Omega-3 could be considered as an effective, less costly strategy in headache/migraine prophylaxis.

B vitamins and their combination could reduce migraine headaches: A randomized double-blind controlled trial.

Background: The B vitamins can potentially help prevent migraine. This study was designed to examine the effects of supplementation with thiamine (B1), pyridoxine (B6), cobalamin (B12), folic acid (B9), and a combination of these vitamins on women with episodic migraine (EM). Methods: This study was a double-blind, placebo-controlled, randomized, clinical trial conducted on 120 women with EM. The participants were divided into the 6 groups of B1 (n = 20), B6 (n = 20), B12 (n = 20), B9 (n = 20), vitamin B complex (n = 20), and placebo (n = 20). Subjects received 1 capsule daily for 12 weeks. As part of the baseline and post-intervention phases, paper-based headache diaries were used to record the number of abortive drugs consumed and the frequency of headache attacks, and the Migraine Disability Assessment Questionnaire (MIDAS) was used to assess migraine disability. Results: A 16-week study on women with EM revealed that the mean changes in the frequency of headache attacks decreased significantly in all vitamin groups in comparison with the placebo group (P < 0.001). In contrast to the placebo, there was also a significant improvement in the migraine disability score in each vitamin group (P < 0.001). The 12-week supplementation with vitamins B9, B1, B6, B12, and B complex also brought on a significant decrease in the use of abortive drugs compared to the placebo group (P = 0.032). Conclusion: The results of this study showed that B1, B6, B12, and B9, and a combination of these vitamins could be effective as an adjuvant in treatment and prophylaxis of EM. Further large trials with long-term follow-ups will be required to confirm our results.

The correlation between serum selenium, zinc, and COVID-19 severity: an observational study.

BACKGROUND: Without an adequate immune response, SARS-CoV2 virus can simply spread throughout the body of the host. Two of the well-known immunonutrients are selenium (Se) and zinc (Zn). Se and Zn deficiency might lead to inflammation, oxidative stress, and viral entry into the cells by decreasing ACE-2 expression; three factors that are proposed to be involved in COVID-19 pathogenesis. Thus, in the current study we aimed at evaluating the correlation between serum Se and Zn status and COVID-19 severity. METHODS: Eighty-four COVID-19 patients were enrolled in this observational study. Patients were diagnosed based on an infectious disease specialist diagnosis, using WHO interim guidance and the recommendations of the Iranian National Committee of Covid-19. The patients with acute respiratory tract infection symptoms were checked for compatibility of chest computed tomography (CT) scan results with that of Covid-19 and Real-time polymerase chain reaction (RT-PCR) for corona virus infection. The severity of Covid-19 was categorized into three groups (mild, moderate, and severe) using CDC criteria. Serum Zn and Se level of all subjects was measured. The severity of the disease was determined only once at the onset of disease. RESULTS: According to the results of linear regression test, there was a significant association between Zn and Se level and COVID-19 severity (ß = - 0.28, P-value = 0.01 for Se; ß = - 0.26, P-value = 0.02). However the significance disappeared after adjusting for confounding factors. Spearman correlation analysis showed a significant negative association between serum Zn, Se and CRP level (r = - 0.35, P-value = 0.001 for Se; r = - 0.41, P-value < 0.001 for Zn). CONCLUSION: Results suggest that increasing levels of Se and Zn were accompanied by a decrease in serum CRP level. However, the significant association between Se, Zn, and disease severity was lost after adjusting for confounding factors.

The effects of vitamin D3 supplementation on TGF-ß and IL-17 serum levels in migraineurs: post hoc analysis of a randomized clinical trial.

BACKGROUND: Although the exact mechanism involved in migraine pathogenesis remained uncertain, and different researches have been developed to address the role of neuroinflammation and immune dysfunction. Therefore, considering the immune protective functions of vitamin D3, we aimed to investigate the effects of daily administration of 2000 IU D3 supplements on serum status of immune markers in migraine patients. METHODS AND MATERIALS: Eighty episodic migraineurs who randomly assigned into two equal groups to receive either vitamin D3 2000 IU/d or placebo for 12-week were enrolled in this placebo-controlled double-blind trial included. Serum concentrations of transforming growth factor-beta (TGF-ß) and interleukin (IL)-17 were evaluated at baseline and after the trial via the ELISA method. RESULTS: Applying ANCOVA adjusted for baseline levels and confounding variables, it was found that the serum level of TGF-ß was significantly higher in vitamin D group (adjusted mean:1665.50 ng/L) than the placebo group (1361.90 ng/L) after the experiment (P-value = 0.012); on the other hand, vitamin D prevented the increment in IL-17 serum level in the intervention group after the trial (adjusted mean:37.84 ng/L) comparing to the controls (adjusted mean:70.09 ng/L; P-value = 0.039). The Pearson correlation analysis revealed a significant positive correlation between changes in serum 25-hydroxy-vitamin D (25(OH)D) and TGF-ß (r = - 0.306, P-value = 0.008). In contrast, no significant correlations were noted between serum 25(OH) D and IL-17 changes throughout the study. CONCLUSION: Based on the results of this study, it was revealed that 12-week vitamin D3 supplementation (2000 IU/day) could enhance the Th17/Treg related cytokines balance in episodic migraineurs. Although these findings are promising, it is needed to be extended. TRIAL REGISTRATION: The trial is registered in the Iranian registry of clinical trials (IRCT) at 11 July 2018, with IRCT code: IRCT20151128025267N6 ( https://www.irct.ir/trial/31246 ).

The effects of vitamin D supplementation on interictal serum levels of calcitonin gene-related peptide (CGRP) in episodic migraine patients: post hoc analysis of a randomized double-blind placebo-controlled trial.

BACKGROUND: Emerging evidence showed promising effects of vitamin D on headaches characteristics. Thus, it seems there is still a need for more researches to clarify the mechanisms by which this vitamin exerts anti-migraine effects. METHODS: The present study was conducted as a 16-week randomized double-blind placebo-controlled trial on 80 episodic migraine patients allocated in 2 parallel groups each consisted of 40 patients who received vitamin D 2000 IU/d or placebo. At baseline and after the intervention completion, headache diaries and migraine disability assessment questionnaire (MIDAS) were used to assess migraine related variables in patients. Also, interictal serum concentration of calcitonin gene-related peptide (CGRP) (as the dominant mediator of migraine pain pathogenesis) was evaluated using ELISA method. RESULTS: The mean (SD) of age in the vitamin D and placebo groups was 37 (8) and 38 (12) years, respectively. ANCOVA test adjusted for baseline values, and confounders showed vitamin D supplementation resulted in a significant improvement in MIDAS score after 12 weeks in the intervention group (21.49 (16.22-26.77)) compared to placebo (31.16 (25.51-36.82) P value: 0.016). Moreover, after controlling for baseline levels, and other variables using ANCOVA, CGRP level was appeared to be significantly lower following vitamin D supplementation (153.26 (133.03-173.49) ng/L) than the patients in the placebo arm (188.35 (167.15-209.54) ng/L) (P value = 0.022). CONCLUSION: According to the current findings, vitamin D supplementation in episodic migraineurs, particularly in those with migraine with aura, may potentially improve migraine headache characteristics and disability probably through attenuating CGRP levels. Therefore, these results could provide a new insight into anti-nociceptive effects of vitamin D; however, more studies are required to confirm our findings. TRIAL REGISTRATION: The trial is registered in the Iranian registry of clinical trials (IRCT) at 11 July 2018, with IRCT code: IRCT20151128025267N6.

Gut-brain Axis and migraine headache: a comprehensive review.

The terminology "gut-brain axis "points out a bidirectional relationship between the GI system and the central nervous system (CNS). To date, several researches have shown that migraine is associated with some gastrointestinal (GI) disorders such as Helicobacter pylori (HP) infection, irritable bowel syndrome (IBS), and celiac disease (CD). The present review article aims to discuss the direct and indirect evidence suggesting relationships between migraine and the gut-brain axis. However, the mechanisms explaining how the gut and the brain may interact in patients with migraine are not entirely clear. Studies suggest that this interaction seems to be influenced by multiple factors such as inflammatory mediators (IL-1ß, IL-6, IL-8, and TNF-α), gut microbiota profile, neuropeptides and serotonin pathway, stress hormones and nutritional substances. Neuropeptides including CGRP, SP, VIP, NPY are thought to have antimicrobial impact on a variety of the gut bacterial strains and thus speculated to be involved in the bidirectional relationship between the gut and the brain. According to the current knowledge, migraine headache in patients harboring HP might be improved following the bacteria eradication. Migraineurs with long headache history and high headache frequency have a higher chance of being diagnosed with IBS. IBS and migraine share some similarities and can alter gut microflora composition and thereby may affect the gut-brain axis and inflammatory status. Migraine has been also associated with CD and the condition should be searched particularly in patients with migraine with occipital and parieto-occipital calcification at brain neuroimaging. In those patients, gluten-free diet can also be effective in reducing migraine frequency. It has also been proposed that migraine may be improved by dietary approaches with beneficial effects on gut microbiota and gut-brain axis including appropriate consumption of fiber per day, adhering to a low glycemic index diet, supplementation with vitamin D, omega-3 and probiotics as well as weight loss dietary plans for overweight and obese patients.

Vitamin D3 might improve headache characteristics and protect against inflammation in migraine: a randomized clinical trial.

INTRODUCTION: Due to anti-inflammatory effects of vitamin D3, we aimed to explore the effects of supplementation with this vitamin on headache characteristics and serum levels of pro/anti-inflammatory markers in migraineurs. METHODS AND MATERIALS: This placebo-controlled, double-blind study included 80 episodic migraineurs who randomly assigned into two equal groups to receive either daily dose of vitamin D3 2000 IU (50 µg) or placebo for 12 weeks. At baseline and after the trial, headache characteristics were determined using diaries and serum levels of interleukin (IL)-10, IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (Cox-2) were assessed via ELISA method. RESULTS: At the end of trial, analysis of covariance (ANCOVA) adjusted for baseline values, and confounders revealed that vitamin D3 supplemented group experienced significantly lower headache days per month (4.71), reduced attacks duration (12.99 h/attack), less severe headaches (5.47, visual analog scale), and lower analgesics use/month (2.85) than placebo group (6.43, 18.32, 6.38 and 4.87, respectively) (P values < 0.05). Using ANCOVA adjusted for baseline levels and confounding variables, it was found that serum levels of IL-10 and Cox-2 did not significantly differ between groups after the experiment; whereas, iNOS serum level was significantly reduced in the intervention group (106.06 U/L) comparing to the controls (156.18 U/L P : 0.001). Also, the patients receiving vitamin D3 yielded a marginally significant lower IL-6 serum concentration (76.43 ng/L) compared to placebo (93.10 ng/L) (P value:0.055). CONCLUSION: Based on the results of this study, we found that 2000 IU (50 µg)/day vitamin D3 supplementation for 12 weeks could improve headache characteristics and might reduce neuro-inflammation in episodic migraine.

A sonographic comparison of the effect of dry needling and ischemic compression on the active trigger point of the sternocleidomastoid muscle associated with cervicogenic headache: A randomized trial.

BACKGROUND: Cervicogenic headache (CeH) is among the common types of headache which has an undesirable influence on the quality of life. The myofascial trigger point (MTrP) within the sternocleidomastoid (SCM) muscle is one of the most important causes of CeH. OBJECTIVE: The purpose of this study was to compare the effect of dry needling (DN) and ischemic compression (IC) on the headache symptoms as well as MTrP-related features in subjects with CeH originating from MTrPs of the SCM muscle using a sonographic method. METHODS: A total of 29 female subjects aged 35.34 ± 12.19 on average with a clinical diagnosis of CeH originating from MTrP in the SCM muscle were randomly divided into the DN, IC, and control groups. Both DN and IC groups received 4 treatment sessions. Headache intensity, duration, frequency, MTrP elastic modulus, MTrP area, and pressure pain threshold (PPT) were assessed 2 weeks before and after treatments. RESULTS: In both DN and IC groups, a significant improvement was found in the headache intensity, duration, frequency, PPT, and MTrP area (P< 0.05). No significant differences were observed between DN and IC (P> 0.05). Pearson correlation revealed a significant correlation between headache intensity and the MTrP elastic modulus (P< 0.05). CONCLUSIONS: Both interventions could reduce headache symptoms, PPT, and MTrP area. Neither intervention was found to be superior to the other in short-term follow-up. IC may be preferred since it has fewer unwanted side effects compared to DN. Based on the data, it may be concluded that some MTrP biomechanical features such as stiffness may influence the produced headache symptoms.

An investigation of oxidant/antioxidant balance in patients with migraine: a case-control study.

BACKGROUND: In recent years, the role of neuroinflammation and oxidative stress in migraine pathogenesis has achieved considerable interest; however, to date findings are equivocal. Thus, the objective of this study was to investigate biomarkers of oxidative stress in episodic and chronic migraineurs (EM and CM patients) and controls. METHODS: Forty-four patients with EM, 27 individuals with CM and 19 age-sex-matched controls were enrolled. After collecting data on demographic and headache characteristics, blood samples were collected and analyzed to detect serum levels of oxidative stress biomarkers (malondialdehyde (MDA) and nitric oxide (NO)); total antioxidant capacity using Trolox equivalent antioxidant capacity (TEAC) assay; and antioxidant enzymes (catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase-1 (GPx-1)). RESULTS: Serum levels of CAT and SOD were significantly lower in the CM group than the EM group and controls. However, serum GPx-1 levels of the CM patients were slightly higher than the EM patients and controls (P-value≤0.001). CM patients had lower mean TEAC values than EM patients and controls. In addition, serum levels of NO and MDA were significantly elevated among subjects with CM compared to EM and control individuals (P-value≤0.001). Pearson correlation analysis revealed negative correlations between the number of days of having headaches per month and serum concentrations of the two antioxidant enzymes CAT (r = - 0.60, P-value< 0.001) and SOD (r = - 0.50, P-value< 0.001) as well as TEAC values (r = - 0.61, P-value< 0.001); however, there were positive correlations between headache days and serum GPx-1 levels (r = 0.46, P-value< 0.001), NO (r = 0.62, P-value< 0.001), and MDA (r = 0.64, P-value< 0.001). CONCLUSION: Present findings highlighted that chronic migraineurs had lower total non-enzymatic antioxidant capacity and higher oxidative stress than episodic migraineurs and control individuals. Although more studies are needed to confirm these data, applying novel prophylactic medications or dietary supplements with antioxidant properties could be promising in migraine therapy.

Association of diet and headache.

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.

Vitamin D in migraine headache: a comprehensive review on literature.

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.

The effects of a multispecies probiotic supplement on inflammatory markers and episodic and chronic migraine characteristics: A randomized double-blind controlled trial.

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.

Molecular Mechanisms of Curcumin in Neuroinflammatory Disorders: A Mini Review of Current Evidences.

OBJECTIVE: Neuroinflammatory disease is a general term used to denote the progressive loss of neuronal function or structure. Many neuroinflammatory diseases, including Alzheimer's, Parkinson's, and multiple sclerosis (MS), occur due to neuroinflammation. Neuroinflammation increases nuclear factor-κB (NF-κB) levels, cyclooxygenase-2 enzymes and inducible nitric oxide synthase, resulting in the release of inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). It could also lead to cellular deterioration and symptoms of neuroinflammatory diseases. Recent studies have suggested that curcumin (the active ingredient in turmeric) could alleviate the process of neuroinflammatory disease. Thus, the present mini-review was conducted to summarize studies regarding cellular and molecular targets of curcumin relevant to neuroinflammatory disorders. METHODS: A literature search strategy was conducted for all English-language literature. Studies that assessed the various properties of curcuminoids in respect of neuroinflammatory disorders were included in this review. RESULTS: The studies have suggested that curcuminoids have significant anti- neuroinflammatory, antioxidant and neuroprotective properties that could attenuate the development and symptom of neuroinflammatory disorders. Curcumin can alleviate neurodegeneration and neuroinflammation through multiple mechanisms, by reducing inflammatory mediators (such as TNF-α, IL-1ß, nitric oxide and NF-κB gene expression), and affect mitochondrial dynamics and even epigenetic changes. CONCLUSION: It is a promising subject of study in the prevention and management of the neuroinflammatory disease. However, controlled, randomized clinical trials are needed to fully evaluate its clinical potential.

Effect of ischemic compression for cervicogenic headache and elastic behavior of active trigger point in the sternocleidomastoid muscle using ultrasound imaging.

OBJECTIVES: To investigate the effect of ischemic compression on clinical outcomes of a cervicogenic headache and elastic behavior of myofascial trigger points. DESIGN: Randomized, controlled trial. SETTING: Outpatient headache clinic. SUBJECTS: 19 subjects with a cervicogenic headache originating from myofascial trigger point within the sternocleidomastoid muscle. INTERVENTIONS: Subjects were randomized in treatment group (n = 9) and control group (n = 10). Subjects in the treatment group received 4 sessions of ischemic compression in the myofascial trigger point region. MAIN MEASURES: Headache intensity, frequency, and duration, trigger point elastic modulus, trigger point area, pressure tolerance, and pressure pain threshold were assessed before and after treatment. RESULTS: Subjects in the treatment group compared with those in control group showed significant improvements in headache intensity (P = 0.002), headache frequency (P = 0.005), headache duration (P = 0.015), pressure tolerance (P < 0.001), pressure pain threshold (P = 0.039), and myofascial trigger point area (P = 0.017). Changes in myofascial trigger point elastic modulus did not reach a significant level (P > 0.05). CONCLUSION: The improvements in outcome measures suggest that ischemic compression may be effective in subjects with a cervicogenic headache associated with a myofascial trigger point in the sternocleidomastoid muscle. Data suggests that biomechanical properties of MTrP and severity of headache symptoms are not directly linked, and other mechanisms could be more influential in contributing to symptoms.

The synergistic effects of ω-3 fatty acids and nano-curcumin supplementation on tumor necrosis factor (TNF)-α gene expression and serum level in migraine patients.

Migraine is a destabilizing neuroinflammatory disorder characterized by recurrent headache attacks. Evidences show tumor necrosis factor (TNF)-α play a role in neuroimmunity pathogenesis of migraine. TNF-α increase prostanoid production, hyperexcitability of neurons, and nociceptor activation resulted in neuroinflammation and neurogenic pain. ω-3 fatty acids and curcumin exert neuroprotective and anti-inflammatory effects via several mechanisms including suppression of TNF-α gene expression and its serum levels. The aim of this study is an evaluation of synergistic effects of ω-3 fatty acids and nano-curcumin on TNF-α gene expression and serum levels in migraine patients. The present study performed as a clinical trial over a 2 month period included 74 episodic migraine patients in 4 groups and received ω-3 fatty acids, nano-curcumin, and combination of them or placebo. At the start and the end of the study, the gene expression of TNF-α and TNF-α serum levels was measured by real-time PCR and ELISA method, respectively. Our results showed that the combination of ω-3 fatty acids and nano-curcumin downregulated TNF-α messenger RNA (mRNA) significantly in a synergistic manner (P < 0.05). As relative to gene expression, a significant greater reduction in serum levels of TNF-α were observed in the combination group, but no significant differences in other groups. Supplementation with ω-3 fatty acids or nano-curcumin alone did not show significant reduction either in mRNA or serum levels of TNF-α. In addition, a much greater reduction in attack frequency was found in the combination group (P < 0.001). These findings indicated that ω-3 fatty acids and curcumin supplementation can be considered as a new promising approach in migraine management.

Molecular mechanisms of omega-3 fatty acids in the migraine headache.

Migraine is a common chronic inflammatory neurological disease with the progressive and episodic course. Much evidence have shown a role of inflammation in the pathogenesis of migraine. Omega-3 fatty acids are an important components of cell membranes phospholipids. The intake of these fatty acids is related to decrease concentration of C-reactive protein (CRP), proinflammatory eicosanoids, cytokines, chemokines and other inflammation biomarkers. Many of clinical trials have shown the beneficial effect of dietary supplementation with omega-3 fatty acids in inflammatory and autoimmune diseases in human, including Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), multiple sclerosis (MS) and migraine headaches. Therefore, omega-3 fatty acids as an alternative therapy can be potentially important. This review focuses on the pathogenesis of a migraine, with an emphasis on the role of omega-3 fatty acid and its molecular mechanisms.

Iranian consensus on use of vitamin D in patients with multiple sclerosis.

BACKGROUND: Accumulating evidences from experimental, epidemiologic and clinical studies support the potential linkage between poor vitamin D status and the risk of developing Multiple Sclerosis (MS), as well as, an adverse disease course. However, the results of the trials on the clinical outcomes of vitamin D supplementation in MS patients are less consistent which brought many discrepancies in routine practice. In this article we presented a summary of a symposium on vitamin D and MS. In this symposium we aim to review the current data about the relationship between vitamin D and MS, and suggest management guides for practicing neurologists. DISCUSSION: Generally, supplementation seems to be reasonable for all MS and clinically isolated syndrome (Rinaldi et al., Toxins 7:129-37, 2015) patients with serum 25(OH)D level below 40 ng/ml. In patients with vitamin D insufficiency or deficiency, a large replacing dose (e.g. 50,000 IU capsules of D per week for 8-12 week) is recommended. Panel also suggested: the checking of the serum vitamin D, and calcium level, as well as, patients' compliance after the initial phase; a maintenance treatment of 1500-2000 IU daily or equivalent intermittent (weekly, biweekly or monthly) Dose, considering the patient's compliance; routine check of serum vitamin D level at least two times a year especially at the beginning of spring and autumn; Serum vitamin D evaluation for first degree relatives of MS patients at high risk age and supplementation in case of insufficiency (25(OH)D less than 40 ng/ml); correction of vitamin D deficiency and insufficiency before pregnancy, as well as, a daily dose of 1500-2000 IU or equivalent biweekly intake in 2nd and 3rd trimesters; stopping supplementation if 25(OH)D serum level exceeds 100 ng/ml. Although the results of high power studies are not available, correcting vitamin D status seems plausible in all MS and CIS patients. Maintaining the serum 25(OH)D level between 40 and 100 ng/ml is not known to exert adverse effect. More ever, it might be associated with lower disease activity.

Effect of Vitamin A Supplementation on fatigue and depression in Multiple Sclerosis patients: A Double-Blind Placebo-Controlled Clinical Trial.

Decreasing the population and activation of inflammatory T helper cells in multiple sclerosis (MS) patients using vitamin A derivatives (retinoic acids) has been well documented. The present study determined the effect of vitamin A supplementation on psychiatric signs in MS patients. The subjects were 101 relapsing-remitting MS patients enrolled in a placebo-controlled randomized clinical trial. The treatment group was administered 25000 IU/d retinyl palmitate (RP) for 6 months followed by 10000 IU/d RP for another 6 months. The results for baseline characteristics, modified fatigue impact scale and Beck Depression Inventory-II were recorded at the beginning and end of the one-year study. The non-normal distribution data was compared between groups using a nonparametric test and normal distribution data was analyzed using a parametric test. (ClinicalTrials.gov Identifiers: NCT01417273). The results showed significant improvement in the treatment group for fatigue (p=0.004) and depression (p=0.01). Vitamin A supplementation helped during interferon therapy in the treatment process and improved psychiatric outcomes for anti-inflammatory mechanisms.

Impact of Vitamin A Supplementation on Disease Progression in Patients with Multiple Sclerosis.

BACKGROUND: Many studies have shown that active vitamin A derivatives suppress the formation of pathogenic T cells in multiple sclerosis (MS) patients. The aim of the present study is to determine the impact of vitamin A on disease progression in MS patients. METHODS: A total of 101 relapsing-remitting MS (RRMS) patients were enrolled in a 1-year placebo-controlled randomized clinical trial. The treated group received 25000 IU/d retinyl palmitate for six month followed by 10000 IU/d retinyl palmitate for another six month. The results of the expanded disability status scale (EDSS) and multiple sclerosis functional composite (MSFC) were recorded at the beginning and the end of the study. The relapse rate was recorded during the intervention. Patients underwent baseline and follow up brain MRIs. RESULTS: The results showed "Mean ± SD" of MSFC changes in the treated group was (-0.14 ± 0.20) and in the placebo group was (-0.31 ± 0.19). MSFC was improved significantly (P < 0.001) in the treatment group. There were no significant differences between the "Mean ± SD" of EDSS changes in the treated (0.07 ± 0.23) and placebo (0.08 ± 0.23) groups (P = 0.73). There were also no significant differences between the "Mean ± SD" of annualized relapse rate in the treated group (-0.36 ± 0.56) and placebo (-0.53 ± 0.55) groups (P = 0.20). The "Mean ± SD" of enhanced lesions in the treatment (0.4 ± 1.0) and in the placebo (0.2 ± 0.6) groups were not significantly different (P = 0.26). Volume of T2 hyperintense lesions "Mean ± SD" was not significantly different between treatment (45 ± 137) and placebo (23 ± 112) groups after intervention (P = 0.23). CONCLUSION: Vitamin A improved total MSFC score in RRMS patients, but it did not change EDSS, relapse rate and brain active lesions.