The association between dietary glycemic index and disease severity among the women with episodic migraine.

PURPOSE: To our knowledge, no studies have evaluated the association between dietary glycemic index (GI) and glycemic load (GL) with migraine-related clinical symptoms. METHODS: This cross-sectional study was conducted among 266 women with episodic migraine. The migraine disability assessment (MIDAS) was used to evaluate migraine-related disability in the recent three months. Visual analogue scales (VAS) were also employed to examine migraine-related pains. Glycemic index and glycemic load indices were calculated using the nutritional information obtained from the food frequency questionnaire. RESULTS: The study participants had a mean age of 34.32 ± 7.86 years. It was observed that individuals in the quartile 4 of GI and GL reported significantly higher consumption of calories, carbohydrates, proteins, and fats (P < 0.05). In the unadjusted models, those in the quartile 4 of GI and GL had significantly increased odds of experiencing severe pain (based on VAS score) (OR = 2.09, 95% CI = 1.37-2.70, P < 0.001 for dietary GI, and OR = 1.75, 95% CI = 1.16-2.79, P = 0.005 for dietary GL). Additionally, compared to participants in the quartile 1 of GI and GL, those in the quartile 4 of GI and GL were more likely to suffer from severe disability (P < 0.05). CONCLUSION: We found a significant positive correlation between the consumption of foods with higher GI and GL and the clinical conditions related to migraine disease. However, due to the cross-sectional nature of the study, it is not possible to establish a cause-and-effect relationship for the observed results.

A Novel Homozygous Variant in the MCOLN1 Gene Associated With Severe Oromandibular Dystonia and Parkinsonism.

BACKGROUND: Mucolipidosis type IV (MLIV) is a rare, progressive lysosomal storage disorder characterized by severe intellectual disability, delayed motor milestones and ophthalmologic abnormalities. MLIV is an autosomal recessive disease caused by mutations in the MCOLN1 gene, encoding mucolipin-1 which is responsible for maintaining lysosomal function. OBJECTIVES AND METHODS: Here, we report a family of four Iranian siblings with cognitive decline, progressive visual and pyramidal disturbances, and abnormal movements manifested by severe oromandibular dystonia and parkinsonism. MRI scans of the brain demonstrated signal abnormalities in the white matter and thinning of the corpus callosum. RESULTS AND CONCLUSIONS: Whole-exome sequencing identified a novel homozygous variant, c.362C > T:p. Thr121Met in the MCOLN1 gene consistent with a diagnosis of MLIV. The presentation of MLIV may overlap with a variety of other neurological diseases, and genetic analysis is an important strategy to clarify the diagnosis. This is an important point that clinicians should be familiar with. The novel variant c.362C > T:p. Thr121Met herein described may be related to a comparatively older age at onset. Our study also expands the clinical spectrum of MLIV associated with the MCOLN1 variants and introduces a novel likely pathogenic variant for testing in MLIV cases that remain unresolved.

The burdens attributable to primary headache disorders in children and adolescents in Iran: estimates from a schools-based study.

BACKGROUND: We recently found headache disorders to be highly prevalent among children (aged 6-11 years) and adolescents (aged 12-17) in Iran (gender- and age-adjusted 1-year prevalences: migraine 25.2%, tension-type headache 12.7%, undifferentiated headache [UdH] 22.1%, probable medication-overuse headache [pMOH] 1.1%, other headache on ≥ 15 days/month [H15+] 3.0%). Here we report on the headache-attributed burden, taking evidence from the same study. METHODS: In a cross-sectional survey, following the generic protocol for the global schools-based study led by the Global Campaign against Headache, we administered the child and adolescent versions of the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) structured questionnaire in 121 schools, purposively selected to reflect the country's diversities. Pupils self-completed these in class, under supervision. Headache diagnostic questions were based on ICHD-3 criteria but for the inclusion of UdH (defined as mild headache with usual duration < 1 h). Burden enquiry was across multiple domains. RESULTS: The analysed sample (N = 3,244) included 1,308 (40.3%) children and 1,936 (59.7%) adolescents (1,531 [47.2%] male, 1,713 [52.8%] female). The non-participating proportion was 3.4%. Mean headache frequency was 3.9 days/4 weeks, and mean duration 1.8 h. Estimated mean proportion of time in ictal state was 1.1% (1.4% for migraine, 16.5% for pMOH). Symptomatic medication was consumed on a mean of 1.6 days/4 weeks. Lost school time averaged 0.4 days/4 weeks overall (2%, assuming a 5-day week), but was eleven-fold higher (4.3 days; 22%) for pMOH. For most headache types, days of reported limited activity were several-fold more than days lost from school (45% for pMOH, 25% for other H15+). Almost one in 12 parents (7.9%) missed work at least once in 4 weeks because of their son's or daughter's headache. Emotional impact and quality-of-life scores reflected these measures of burden. CONCLUSIONS: Headache, common in children and adolescents in Iran, is associated with symptom burdens that may be onerous for some but not for most. However, there are substantial consequential burdens, particularly for the 1.1% with pMOH and the 3.0% with other H15+, who suffer educational disturbances and potentially major life impairments. These findings are of importance to educational and health policies in Iran.

Secondary headache disorders in Turkey, the Middle East, Asia, and Africa: A cross-sectional, multicenter study.

BACKGROUND: This multicenter cross-sectional study aimed to determine the frequency and characteristics of secondary headaches in different geographic regions, including Turkey, the Middle East, Asia, and Africa. METHODS: Patients were admitted to the study on a particular day each week for five consecutive weeks between 1 April and 16 May 2022. Before the study, all researchers underwent a constructed briefing about the use and code of the ICHD-3 criteria. The study was conducted in two stages. In the first stage, data on secondary headaches were compared between the regions. In the second stage, the sub-diagnoses of secondary headaches were analyzed only in Turkey. RESULTS: A total of 4144 (30.0%) of the 13,794 patients reported headaches as the main symptoms at admission. A total of 422 patients were excluded from the study. In total, 1249 (33.4%) of 3722 patients were diagnosed as having secondary headaches (Turkey [n = 1039], Middle East [n = 80], Asia [n = 51], Africa [n = 79]). The frequency of secondary headaches (Turkey 33.6%, Africa 30.1%, Middle East 35.5%, Asia 35.4%) did not differ significantly between the regions (p > 0.05). The most common subtype of secondary headaches was headache attributed to substances or their withdrawal in all the studied regions. There was a female predominance in all regions, but it was lower in Africa than in Turkey. The severity and density of headaches differed significantly between the regions, with patients from Africa reporting milder pain than patients from other regions. In Turkey, the most common sub-diagnoses of secondary headaches were medication overuse headache, idiopathic intracranial hypertension, and cervicogenic headache. CONCLUSION: In the present study, one in three patients with a headache had a secondary headache. Headache attributed to substances or their withdrawal was the most common subtype of secondary headaches in all the studied regions. The female predominance of secondary headaches was lower in Africa than in Turkey. The severity and density of headaches differed significantly between regions, with patients from Africa reporting milder pain.

Guidelines of the International Headache Society for Controlled Clinical Trials in Idiopathic Intracranial Hypertension.

The quality of clinical trials is essential to advance treatment, inform regulatory decisions and meta-analysis. With the increased incidence of idiopathic intracranial hypertension and the emergence of clinical trials for novel therapies in this condition, the International Headache Society Guidelines for Controlled Clinical Trials in Idiopathic Intracranial Hypertension aims to establish guidelines for designing state-of-the-art controlled clinical trials for idiopathic intracranial hypertension.

The prevalence and characteristics of visceral autonomic symptoms among migraineurs: A population-based study.

BACKGROUND: There is limited evidence about visceral autonomic symptoms in the different phases of migraine attack. We evaluated the prevalence of these symptoms in migraineurs before, during, and after headache attacks. In addition, the association between migraine characteristics and visceral autonomic symptoms was investigated. METHODS: A total of 605 participants who met the entry criteria were enrolled prospectively in this cross-sectional study. Participants were 18-60 years old and met the ICHD-3 criteria for migraine with or without aura. Information on the migraine symptoms was gathered from all participants in face-to-face interviews. A structured questionnaire was used to evaluate the related symptoms before, during, and after attacks. Migraine features of frequency, duration, and severity were also assessed. RESULTS: Considering all phases, the most commonly present visceral symptom was nausea (52.9%). About half of participants reported at least one visceral symptom before the onset of attacks. While, during and after attacks, 71% and 36% of participants reported such characteristics, respectively. Notably, the migraine headache in participants with visceral symptoms was longer during attacks compared to participants without them (24.4 ± 29.6 vs. 16.8 ± 19.8; P = 0.008). Additionally, subjects with positive visceral symptoms experienced more severe migraine attacks than participants without symptoms for both the premonitory (8 ± 1.7 vs. 7.6 ± 1.8; P = 0.02) and during-attack (8.01 ± 1.7 vs. 7.09 ± 1.9; P = 0.001) phases. CONCLUSION: This study demonstrated that visceral symptoms were common in migraine sufferers not only during attacks but also in the premonitory and postdrome phases. Positive visceral symptoms were also associated with more burdensome headache attacks. Therefore, recognizing the phenotypic presentation of associated symptoms of migraine, especially during the pre-attack phase, could aid in early implementation of optimal management.

The prevalence of headache disorders in children and adolescents in Iran: a schools-based study.

BACKGROUND: While the Global Burden of Disease study reports headache disorders as the third-highest cause of disability worldwide, the headache data in this study largely come from adults. This national study in Iran, the first of its type in the Eastern Mediterranean Region, was part of a global schools-based programme within the Global Campaign against Headache contributing data from children (6-11 years) and adolescents (12-17 years). METHODS: We followed the generic protocol for the global study. In a cross-sectional survey, self-completed structured questionnaires were administered to pupils within their classes in 121 schools selected from across the country to be representative of its diversities. Headache diagnostic questions were based on ICHD-3 criteria but for the inclusion of undifferentiated headache. RESULTS: Of 3,357 potential participants, 3,244 (children 1,308 [40.3%], adolescents 1,936 [59.7%]; males 1,531 [47.2%], females 1,713 [52.8%]) satisfactorily completed the questionnaire. Children and males were therefore somewhat under-represented, with a participating proportion of 96.6%. Gender- and age-adjusted 1-year prevalence of any headache was 65.4%, of migraine 25.2%, of tension-type headache 12.7%, of undifferentiated headache 22.1%, of all headache on ≥15 days/month 4.1%, and of probable medication-overuse headache 1.1%. All headache types except undifferentiated headache were more prevalent among adolescents than children; probable medication-overuse headache increased five-fold between childhood and adolescence. CONCLUSIONS: Headache disorders are common in children and adolescents in Iran, with undifferentiated headache accounting for over one third of cases. The increasing prevalence of probable medication-overuse headache with age is concerning. These findings are of importance to health and educational policies in Iran.

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.

Characteristics and comorbidities of headache in patients over 50 years of age: a cross-sectional study.

BACKGROUND: Although headache is a common complaint in younger individuals, it is one of the most common complaints among persons over the age of 50 and is a significant cause of morbidity. As there are differences in the causes and types of headache, the diagnosis and management of headache in older adults differ from that in younger individuals. METHODS: In this cross-sectional study, 570 patients ≥ 50 years were recruited at a university affiliated tertiary headache center between 2016 and 2019. Demographic data, headache characteristics, and comorbid medical conditions were recorded. The presence of depression was explored using the Beck Depression Inventory. The patients were evaluated using the STOP-BANG scale to determine the risk of obstructive sleep apnea. RESULTS: The mean age of the patients was 57.7 years. Seventy-three percent of the patients had primary headache disorders, with the most prevalent types being migraine, followed by tension-type headache. Secondary headaches were primarily the result of overuse of medication, cervical spine disease, and hypertension. Patients with medication-overuse headache were significantly more likely to suffer from hypothyroidism and gastrointestinal problems such as bleeding/ulcers. Irritable bowel syndrome was also more common in patients with medication-overuse headaches and migraines. The risk for obstructive sleep apnea was intermediate in 45.2% of the patients with hypertension-induced headache, but was lower in the majority of others. There was a high tendency for moderate-to-severe depression in the participants; however, the Beck Depression Inventory scores were significantly higher in medication-overuse headache patients. CONCLUSION: Proper treatment of headache in middle-aged and older adults requires the recognition of secondary causes, comorbid diseases, and drug induced or medication overuse headaches. Special attention should be paid to depression and obstructive sleep apnea in such patients suffering from headache disorders.

Assessment of peripheral biomarkers potentially involved in episodic and chronic migraine: a case-control study with a focus on NGF, BDNF, VEGF, and PGE2.

BACKGROUND: Several inflammatory and vascular molecules, and neurotrophins have been suggested to have a possible role in the development of migraine. However, pathophysiological events leading to migraine onset and transformation of episodic migraine (EM) to chronic migraine (CM) are not fully understood. Thus, we aimed to assess peripheral levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE2) in EM and CM patients, and controls. METHODS: From September 2017 to June 2020, 89 subjects were enrolled in a case-control study; 23 and 36 EM and CM patients, respectively, and 30 age and sex-matched controls. Demographic data and medical history were obtained from all patients. Headache characteristics were recorded at baseline visit and ensuing 30 days for persons with migraine disease. Serum levels of NGF, BDNF, VEGF, and PGE2 were measured once for controls and EM and CM patients, and adjusted for age, sex, and body mass index. RESULTS: Serum levels of NGF were significantly lower in EM patients compared to controls and CM patients (P-value=0.003 and 0.042, respectively). Serum levels of BDNF were significantly lower in EM and CM patients as opposed to controls (P-value<0.001), but comparable between EM and CM patients (P-value=0.715). Peripheral blood levels of VEGF were significantly higher in EM and CM patients as opposed to controls (P-value<0.001), but not different between EM and CM patients (P-value=0.859). Serum levels of PGE2 were significantly lower in EM patients compared to controls (P-value=0.011), however similar between EM and CM patients (P-value=0.086). In migraine patients, serum levels of NGF and PGE2 positively correlated with headache frequency (NGF: ρ = 0.476 and P-value<0.001; PGE2: ρ = 0.286 and P-value=0.028), while corresponding levels of BDNF and VEGF did not correlate with headache frequency (BDNF: ρ = 0.037 and P-value=0.778; VEGF: ρ= -0.025 and P-value=0.850). CONCLUSIONS: Our findings suggest that NGF, BDNF, PGE2, and VEGF may play a significant role in migraine pathogenesis and/or chronification, and therefore might bear potential value for novel targeted abortive and prophylactic migraine therapy. Further prospective cohort studies with larger sample sizes can more robustly evaluate the implications of these findings.

Cranial autonomic symptoms in episodic and chronic migraine: a cross sectional study in Iran.

BACKGROUND: Cranial autonomic symptoms are common in migraine, with eye redness and tearing being the most common ones. Their identification can help to avoid misdiagnosis, predict the disease course, and select the appropriate treatment. METHODS: This was a cross-sectional study of 904 patients who presented with migraine to a headache referral clinic. The participants filled out a questionnaire about their headache characteristics, as well as the presence of cranial autonomic symptoms. A total of 904 patients, 698 women (77.2%) and 206 men (22.8%), were included in the study, with a mean (SD) age of 38.05 (11.76) years. RESULTS: About 70% of subjects with chronic migraine and 56.2% of those with episodic migraine reported one or more cranial autonomic symptoms. The two most commonly reported autonomic symptoms were eye redness (36.06%) and tearing (21.02%). Chronic migraine (43.4% vs. 29.5%), unilateral headache (56.8% vs. 48.7%), and blurred vision (20% vs. 14.7%) were significantly more frequent in migraineurs with cranial autonomic symptoms. Headache intensity and frequency in subjects with cranial autonomic symptoms were significantly higher than in those without cranial autonomic symptoms. CONCLUSION: We found higher percentages of cranial autonomic symptoms in patients with unilateral headaches, frequent and severe attacks and blurred vision. A diagnosis of cranial autonomic symptoms accompanying migraine may predict more severe disease and the possibility of evolution into chronic migraine.

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.

Association of dietary diversity score (DDS) and migraine headache severity among women.

BACKGROUND AND OBJECTIVES: Migraine is an episodic disorder that is characterized by unilateral headache lasting 4-72 h along with certain associated features. Modifying dietary habits have been considered an appropriate therapeutic approach in these patients. This study was designed to examine the association between dietary diversity score (DDS) and severity, frequency, and duration of migraine attacks. METHODS AND MATERIALS: The present study was conducted using a cross-sectional design on 256 women 18-50 years old referred to neurology clinics for the first time. After the diagnosis of migraine by a neurologist, the data related to anthropometric measures and dietary intake (147-item semi-quantitative food frequency questionnaire) were collected. To assess migraine severity, the migraine disability assessment questionnaire (MIDAS), visual analog scale (VAS), and a 30-day headache diary were used. Multinomial logistic regression was used to evaluate the association between DDS and migraine severity. The age, physical activity, BMI, and job were considered confounding variables in regression model. Data were analyzed using SPSS software and P values < 0.05 considered statistically significant. RESULTS: Totally, 256 subjects participated in the present study with mean age, height, weight, and BMI of 34.28 ± 7.88 years, 161.78 ± 5.18 cm, 69.25 ± 13.06 kg, and 26.46 ± 4.89 kg/m2, respectively. Subjects with higher DDS had a lower waist circumference (P = 0.01). There was no association between DDS and other anthropometric measures and demographic characteristics (P > 0.05). In the crude model of logistic regression, participants with lower DDS had higher odds of more pain severity (OR = 2.30; 95% CI = 1.28, 4.12; P = 0.005), migraine disability (OR = 2.66; 95% CI = 1.51, 4.69; P = 0.001), and headache duration (OR = 2.32; CI = 1.22, 4.40; P = 0.01) compared to reference group. No association was found between headache frequency and DDS. Adjusting for the effect of confounding variables did not change the significant association. CONCLUSION: DDS was inversely associated with migraine disability, pain severity, and headache frequency. Additional studies are needed to replicate these findings and to explore mechanisms that mediate the association between DDS and migraine attacks.

Economic burden of medication-overuse headache in Iran: direct and indirect costs.

BACKGROUND AND OBJECTIVE: Medication-overuse headache (MOH) as a secondary chronic headache imposes a considerable burden on both individuals and societies. Nevertheless, little is known about the burden of MOH in Iran. Therefore, in the current study, we aimed to quantify the annual cost of MOH among Iranian patients. METHODS: In this cross-sectional study, 84 patients were recruited. Demographic data, headache attack characteristics, related disability, and information about the economic burden of MOH were collected through face-to-face interview. Direct medical and nonmedical costs as well as indirect costs were included in our cost analysis. The prevalence-based approach was applied to estimate the economic burden of MOH. RESULTS: We found that MOH patients in Iran spend averagely $1046 for medical services, $132 for nonmedical services, and $1432 due to lost productivity per year. The per-person annual cost of MOH was US$2610, and the total annual cost for Iran was $10,179,000,000, with direct and indirect cost accounting for 45% and 55%, respectively. CONCLUSION: MOH leads to substantial healthcare costs and significant loss of productivity in Iran. Therefore, raising awareness in this area especially for policymakers can use in future health planning and lead to resource allocation in the field of disabling type of headache disorders such as MOH. Our findings also provide a different insight into the burden of MOH, which are likely closer to the actual costs in middle- and low-income countries, and also it could be a sample of such a study in western Asia.

Reversible cerebral vasoconstriction syndrome (RCVS): an interesting case report.

BACKGROUND: Reversible Cerebral Vasoconstriction Syndrome is a condition of transient cerebral vascular spasms, which usually presents with recurrent thunderclap headaches and recovers within 3 months. Several probable triggers and underlying factors, such as sex hormones, vasoactive drugs, head trauma or surgery, and tumors, have been implicated. CASE PRESENTATION: In this paper, we present a 53-year-old woman with thunderclap headaches and normal lab tests who was radio-clinically diagnosed with reversible cerebral vasoconstriction syndrome and treated accordingly. Then, she experienced the recurrence of RCVS after about 2 years and headaches after 1 year in association with high blood pressure, high blood sugar, hypothyroidism, hyperlipidemia, and a urine metanephrine level of 5 times higher than the normal limit, suggesting a diagnosis of pheochromocytoma. After confirmation of the diagnosis with further imaging studies, surgical removal of the tumor resolved all the signs and symptoms. CONCLUSION: Often underdiagnosed, pheochromocytoma could be an important condition associated with RCVS. It is important for clinicians to bear this diagnosis in mind while dealing with similar cases of recurrent thunderclap headaches.

Structured headache services as the solution to the ill-health burden of headache: 1. Rationale and description

In countries where headache services exist at all, their focus is usually on specialist (tertiary) care. This is clinically and economically inappropriate: most headache disorders can effectively and more efficiently (and at lower cost) be treated in educationally supported primary care. At the same time, compartmentalizing divisions between primary, secondary and tertiary care in many health-care systems create multiple inefficiencies, confronting patients attempting to navigate these levels (the "patient journey") with perplexing obstacles.High demand for headache care, estimated here in a needs-assessment exercise, is the biggest of the challenges to reform. It is also the principal reason why reform is necessary.The structured headache services model presented here by experts from all world regions on behalf of the Global Campaign against Headache is the suggested health-care solution to headache. It develops and refines previous proposals, responding to the challenge of high demand by basing headache services in primary care, with two supporting arguments. First, only primary care can deliver headache services equitably to the large numbers of people needing it. Second, with educational supports, they can do so effectively to most of these people. The model calls for vertical integration between care levels (primary, secondary and tertiary), and protection of the more advanced levels for the minority of patients who need them. At the same time, it is amenable to horizontal integration with other care services. It is adaptable according to the broader national or regional health services in which headache services should be embedded.It is, according to evidence and argument presented, an efficient and cost-effective model, but these are claims to be tested in formal economic analyses.

Cinnarizine and sodium valproate as the preventive agents of pediatric migraine: A randomized double-blind placebo-controlled trial.

BACKGROUND: Few migraine preventive agents have been assessed in a pediatric population. We evaluated the safety and efficacy of cinnarizine and sodium valproate for migraine prophylaxis in children and adolescents. METHODS: We carried out a randomized double-blind placebo-controlled trial in the Children's Medical Center and Sina hospital, Tehran, Iran. Eligible participants were randomly assigned in 1:1:1 ratio via interactive web response system to receive either cinnarizine, sodium valproate, or placebo. The primary endpoints were the mean change in frequency and intensity of migraine attacks from baseline to the last 4 weeks of trial. The secondary endpoint was the efficacy of each drug in the prevention of migraine. The drug was considered effective if it decreased migraine frequency by more than 50% in the double-blind phase compared with the baseline. Safety endpoint was adverse effects that were reported by children or their parents. RESULTS: A total of 158 children participated. The frequency of migraine attacks significantly reduced compared to baseline in cinnarizine (difference: -8.0; 95% confidence interval (CI): -9.3 to -6.6), sodium valproate (difference: -8.3; 95% confidence interval: -9.3 to -7.2), and placebo (difference: -4.4; 95% confidence interval: -5.4 to -3.4) arms. The decrease was statistically greater in cinnarizine (difference: -3.6; 95% confidence interval: -5.5 to -1.6) and sodium valproate (difference: -3.9; 95% confidence interval: -5.8 to -1.9) arms, compared to placebo group. Children in all groups had significant reduction in intensity of episodes compared to baseline (cinnarizine: -4.6; 95% confidence interval: -5.2 to -4.0; sodium valproate: -4.0; 95% confidence interval: -4.8 to -3.3; placebo: -2.6; 95% confidence interval: -3.4 to -1.8). The decrease was statistically greater in cinnarizine (difference: -2.0; 95% confidence interval: -3.2 to -0.8) and sodium valproate (difference: -1.5; 95% confidence interval: -2.7 to -0.3) arms, compared to the placebo group. Seventy-one percent of individuals in the cinnarizine group, 66% of cases in the sodium valproate group, and 42% of people in the placebo arm reported more than 50% reduction in episodes at the end of the trial. The odds ratio for >50% responder rate was 3.5 (98.3% confidence interval: 1.3 to 9.3) for cinnarizine versus placebo and 2.7 (98.3% confidence interval: 1.0 to 6.9) for sodium valproate versus placebo. Nine individuals reported adverse effects (three in cinnarizine, five in sodium valproate, and one in the placebo group) and one case in the sodium valproate group discontinued the therapy due to severe sedation. CONCLUSION: Cinnarizine and sodium valproate could be useful in migraine prophylaxis in children and adolescents. Trial registration: IRCT201206306907N4.

Associations between adherence to dietary approaches to stop hypertension (DASH) diet and migraine headache severity and duration among women.

Purpose/introduction: Migraine is a common disorder, with attacks causing neurological dysfunction and pain. Many foods are involved in reducing the severity of migraine attacks. This study aimed to assess the effects that adhering to the Dietary approaches to stop hypertension (DASH) diet had on headache severity and duration among women suffering from migraine.Methods and materials: Two hundred and sixty-six women (18-45 years) were enrolled after being referred to a headache clinic for the first time. Dietary intake was assessed daily using a Food Frequency Questionnaire. Anthropometric measurements were assessed for all cases, as well as headache duration of each attack; Visual Analog Scale and Migraine Disability Assessment questionnaires were evaluated by a neurologist.Results: The mean age, weight, and height of the study participants were 34.32 (SD 7.86) years, 69.41 (13.02) kg, and 161 (0.05) cm, respectively. The results of analysis in the crude model showed that individuals with the greatest adherence to the DASH diet displayed a 30% lower prevalence in severe headaches, compared to those with the lowest adherence (OR=0.70, 95%CI=0.49-0.99, P<0.05). Also, after controlling for potential confounders, subjects in the highest quartile of DASH diet adherence were 46% less likely to have severe headaches, and also saw a 36% lower occurrence of moderate headaches, compared to those in the bottom quartile (OR=0.54, 95%CI=0.35-0.83, P<0.005 and OR=0.64, 95%CI=0.44-0.95, P<0.005, respectively). These results showed a significant positive correlation between adherence to DASH diets and lower rates of mean headache duration for each attack in the last month (ß=-1.49, CI=0.21-2.7, P=0.02).Conclusion: This study showed that the DASH diet is associated with lower headache severity and duration in migraine 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.

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.