Severe Migraine Attacks Research Articles

Relationship of inflammatory factors with migraine in patients with patent foramen ovale undergoing percutaneous closure

Abstract Background Observational studies have reported the incidental reduction of the frequency and severity of migraine attacks following transcatheter patent foramn ovale (PFO) for established indications. Possible physiologic mechanisms for a relationship between PFO and migraine, if such a link does exist, have been the subject of much speculation, with some researchers suggesting the possible role of PFO as a conduit for the passage of various migraine-inducing inflammatory, vasoactive triggers in cerebral circulation. Purpose The aim of this study was to compare the levels of inflammatory mediators between migraineurs and non –migraineurs and to investigate the impact of PFO closure on the inflammatory state of individuals with migraine and alleviation of migraine symptoms. Methods Forty-five patients (mean age 48.2 ± 10.8 years, 48% male) undergoing percutaneous PFO closure were enrolled in the study. Among them, 15 patients reported recurrent migraine episodes (mean age 46.4 ± 8.90 years, 86% female) while 30 individuals (mean age 49 ± 12.32 years, 70% male) were non-migraineurs. White blood cell count, C-reactive protein (CRP), ferritin and d-dimers levels, as well as the erythrocyte sedimentation rate (ESR) were compared between migraineurs and non-migraineurs. We additionally analyzed the inflammatory levels before and after the percutaneous PFO closure in migraineurs, correlating these changes with migraine relief assessed using the Migraine Disability Assessment Questionnaire (MIDAS) over a 6-month follow-up period. Results White blood cell count, d-dimers levels and ESR were similar in migraineurs and non-migraineurs (6,583 ± 2,251 Χ1 0.e3/uL vs 6,115 ± 1,958 Χ10.e3/uL; p-value = 0.48; 0.54 ± 0.49 μg/L vs 0.45 ± 0.29 μg/L; p- value= 0.49; 23.08 ± 16.68 mm vs 18.51 ± 14.98 mm; p- value 0.402; respectively). However, CRP and ferritin levels were significantly greater in patients with migraine compared to non- migraineurs (3.82 ± 1.87 mg/L vs 1.34 ± 1.52 mg/L; p- value =0.037 and 111.21 ± 82.70 ng/ml vs 50.12 ± 47.9 ng/ml; p- value = 0.023, respectively). Moreover, there was no significant difference between pre- and post-procedural inflammatory levels in migraineurs undergoing percutaneous PFO closure. Of note, following the procedure a reduction in CRP levels was observed without, however, reaching statistical significance. Finally, all patients observed a cessation in the occurrence of migraine attacks after closure. Conclusions Our study revealed significantly higher baseline levels of CRP and ferritin in migraineurs compared to non-migrainers with PFO. Although no alteration in inflammatory factors was observed following the procedure in migraineurs with PFO, all individuals experienced relief from migraine symptoms. Given the limitation of our study due to the small sample size, future studies may provide more insights into the potential benefits of PFO closure in specific migraine patient phenotypes.

Experience of using Russian rizatriptan 10 mg tablets in routine clinical practice: results of a multicenter post-registration observational study “OPYT”

One of the key mediator systems involved in the pathogenesis of migraine is the serotonergic system, which led to the development and introduction of serotonin 5-HT1 receptor agonists (triptans) into clinical practice as the most important means of preventing migraine attacks. Serotonin 5-HT1 receptor agonists have a high selectivity for the 5-HT1B and 5-HT1D receptor subtypes, which ensures their effect on the pathogenesis of migraine attack development.Objective: to evaluate the efficacy of a standard dose of Relonova in the relief of four moderate to severe migraine attacks in outpatients in reallife clinical practice, including assessment of the rate of attack relief, the effect of the drug on headache intensity, concomitant symptoms and the general condition of the patient.Material and methods. The study involved 415 patients with migraine (319 women and 96 men; mean age 35.7±7.8 years). A total of 1660 migraine attacks were analyzed. The average number of migraine days per month was 6.72±3.99. Migraine attacks with aura were observed in 125 patients (30.1%). Patients stopped four migraine attacks and filled out self-monitoring diaries. Treatment efficacy was assessed according to the European Headache Federation (EHF) Consensus Algorithm for Determining Effective Treatment of a Migraine Attack.Results. After taking Relonova, pain became mild or disappeared completely in 30 minutes in 52% of patients, in 76% in 1 hour, in 93% in 2 hours, in 99% in 4 hours and in 99% of patients in 24 hours. A recurrence of the headache occurred in 8.8% of the attacks. Additional analgesic treatment after 30 minutes was required in 14% of cases, after which period the frequency did not exceed 2%. Adverse events were observed in 4% of patients and were mild. The overwhelming majority (90%) of study participants were able to successfully terminate three attacks and were responders.Conclusion. Relonova is an effective and safe agent to stop migraine attack and can be recommended for use in daily clinical practice.

Effectiveness of combining greater occipital nerve block and pulsed radiofrequency treatment in patients with chronic migraine: a double-blind, randomized controlled trial

BackgroundPulsed radiofrequency (PRF) treatment targeting the greater occipital nerve (GON) has shown efficacy in treating various conditions. This double-blind, randomized controlled study aimed to evaluate the effects of combining PRF therapy with GON block (GONB) therapy in patients with chronic migraine.MethodsThe study consisted of two groups: GONB and GONB + PRF, each comprising 16 patients with chronic migraine. Using 0.5-Hz sensorial stimulation, a 5-cm-long radiofrequency needle was inserted under ultrasound guidance in both groups. Subsequently, all patients received a GONB by administering 2 mL of 0.25% bupivacaine. In the GONB + PRF group, patients underwent 4 min of PRF at 42℃, whereas the GONB group did not receive any PRF treatment. Follow-up examinations were performed at 1, 2, 3 and 6 months after the procedure to evaluate the frequency and severity of migraine attacks, number of headache days, and analgesic consumption.ResultsIn the GONB + PRF group, the visual analog scale (VAS) score, number of migraine attacks, number of headache days, and analgesic consumption were significantly lower compared to the GONB group (P < 0.05). Significant decreases (60%) in mean VAS scores, number of migraine attacks, number of headache days, and consumption of analgesic medications were observed in the GONB + PRF group at the 1-, 2-, 3-, and 6-month follow-ups compared with the pre-treatment period (P < 0.05).ConclusionsThe combination of GONB and PRF presents a promising new treatment option for patients with chronic migraine. This approach has demonstrated efficacy in minimizing analgesic use, decreasing the frequency of migraine attacks, reducing the number of headache days and decreasing the severity of migraine attacks.Trial RegistrationNCT05464212.

Comparison of the Efficacy of Propranolol Versus Valsartan in the Prevention of Migraine: A Randomized Controlled Trial

BackgroundMigraine is a prevalent episodic headache that affects approximately 14%-15% of the global population. Since valsartan is an antihypertensive drug, it is hypothesized that taking valsartan can prevent migraine attacks in patients with the condition. This study aimed to determine the efficacy of propranolol versus valsartan in preventing migraine attacks. Material and MethodsThis randomized controlled trial was conducted on 56 patients with migraine from a neurology clinic. Patients were divided into two equal groups of 28 individuals, after providing informed consent. The patients then received either propranolol or valsartan treatment. The intensity and frequency of migraines were compared before and after treatment in both study groups. ResultsThe patients’ mean age was 32.78 years old (±6.9 SD), and 64% of the patients were female. After a 1-month treatment period, the results showed that valsartan patients experienced significantly fewer severe migraine attacks compared to propranolol patients. ConclusionAccording to the results of the present study, valsartan may be at least as effective as propranolol and perhaps more effective on some measures.

Long-term safety of zavegepant nasal spray for the acute treatment of migraine: A phase 2/3 open-label study.

Zavegepant is the first small molecule calcitonin gene-related peptide receptor antagonist for intranasal administration for the acute treatment of migraine. The objective of this study was to evaluate the safety and tolerability of zavegepant in the acute treatment of migraine under repeated, as-needed dosing for up to one year. This phase 2/3, one-year open-label safety study of zavegepant 10 mg nasal spray for the acute treatment of migraine enrolled adults aged ≥18 years with a history of two to eight moderate to severe monthly migraine attacks. Participants used one dose of zavegepant as needed to self-treat migraine attacks of any severity, up to eight times per month, for 52 weeks. Participants were enrolled between 29 June and 4 December 2020. Of the 608 participants entering long-term treatment, 603 were treated with study drug. Participants administered a mean (SD) of 3.1 (1.55) zavegepant doses per month. There were no deaths. Of the seven serious adverse events reported, none was considered related to treatment. Altogether, 6.8% (41/603) of treated participants had an adverse event leading to study drug discontinuation. The most frequent adverse event leading to discontinuation was dysgeusia (1.5% [9/603]). The most common treatment-emergent adverse events (≥5% of participants) were dysgeusia (39.1% [236/603]); nasal discomfort (10.3% [62/603]); COVID-19 (7.5% [45/603]); nausea (6.1% [37/603]); nasal congestion and throat irritation (5.5% [33/603] each); and back pain (5.3% [32/603]). Aminotransferases >3x the upper limit of normal occurred in 2.6% [16/603] of participants; none had concurrent elevations in bilirubin >2x upper limit of normal. One year of zavegepant 10 mg nasal spray up to eight times per month was safe and well tolerated.Trial registration: Clinicaltrials.gov: NCT04408794.

The Modern Clinician as an "Argonaut" Guiding Through the "Symplegades" of Evidence for PFO Closure in Patients With Migraine.

Patent foramen ovale (PFO) has been associated with migraine, especially migraine with aura, and 30-50% of individuals with migraine with aura have a PFO, suggesting it could be more than just an "innocent bystander''. Observational data showed a reduction of the frequency and severity of migraine attacks, particularly those with aura, following transcatheter PFO closure for established indications. Three small randomized controlled trials have demonstrated significant benefits of PFO closure in most of their secondary endpoints, such as reductions in the mean number of monthly migraine attacks and migraine days. Since a significant proportion of patients experience important side effects from traditional migraine medications and newer highly effective migraine prevention strategies may need to be instituted. PFO closure could in this regard to be a valuable add-on in the armamentarium of migraine treatment, improving the quality of life by alleviating the need for medications. The effect of percutaneous PFO closure on migraine treatment is needed to be clarified. As the underlying pathophysiology remains poorly understood and largely hypothetical, future investigations, focusing on the causal relationship between PFO and migraine, will help to define the subgroup of patients most likely to benefit from PFO closure. More accurate patient recruitment may lead to greater postprocedural benefits and more significant symptom improvement. Additionally, randomized controlled trials need to be reported adequately with more realistic endpoints, sufficient duration of follow-up, and statistical power to detect differences between closure and placebo groups to ensure precise and reliable findings.

Real-world approaches to outpatient treatment of status migrainosus: A survey study.

Identify how the American Headache Society (AHS) membership manages status migrainosus (SM) among outpatients. SM is defined as a debilitating migraine attack lasting more than 72 h. There is no standard of care for SM, including whether a 72-h duration is required before the attack can be treated as SM. The Refractory Headache Special Interest Group from AHS developed a four-question survey distributed to AHS members enquiring (1) whether they treat severe refractory migraine attacks the same as SM regardless of duration, (2) what their first step in SM management is, (3) what the top three medications they use for SM are, and (4) whether they are United Council for Neurologic Subspecialties (UCNS) certified. The survey was conducted in January 2022. Descriptive statistical analyses were performed. Responses were received from 196 of 1859 (10.5%) AHS members; 64.3% were UCNS certified in headache management. Respondents treated 69.4% (136/196) of patients with a severe refractory migraine attack as SM before the 72-h period had elapsed. Most (76.0%, 149/196) chose "treat remotely using outpatient medications at home" as the first step, 11.2% (22/196) preferred procedures, 6.1% (12/196) favored an infusion center, 6.1% (12/196) sent patients to the emergency department (ED) or urgent care, and 0.5% (1/196) preferred direct hospital admission. The top five preferred medications were as follows: (1) corticosteroids (71.4%, 140/196), (2) nonsteroidal anti-inflammatory drugs (NSAIDs) (50.1%, 99/196), (3) neuroleptics (46.9%, 92/196), (4) triptans (30.6%, 60/196), and (5) dihydroergotamine (DHE) (21.4%, 42/196). Healthcare professionals with expertise in headache medicine typically treated severe migraine attacks early and did not wait 72 h to fulfill the diagnostic criteria for SM. Outpatient management with one or more medications for home use was preferred by most respondents; few opted for ED referrals. Finally, corticosteroids, NSAIDs, neuroleptics, triptans, and DHE were the top five preferred treatments for home SM management.

Real-world experiences of migraine patients on Erenumab: a Kuwait single center cohort

ABSTRACT Background Migraine is a prevalent headache disorder with a significant impact on the quality of life. This study aims to investigate the effectiveness and safety of erenumab, mAb targeting the CGRP receptor, in treating chronic (CM) and episodic (EM) migraine in clinical practice Kuwait, providing region-specific insights to treatment options. Method This was a prospective observational cohort study of patients diagnosed with EM or CM treated with erenumab. The primary outcome of the study was to assess the proportion of patients achieving ≥ 50% reduction in monthly mean migraine days, and several changes including the mean number of monthly migraine days, the frequency of analgesic use, attack severity, AEs, and QoL. Results The study included 151 patients with a mean age of 44.0±11.4 years, and 81.9% female. The primary outcome was achieved in 74.2% of patients, with a significant (p < 0.001) reduction in headache frequency, pain severity, analgesic use, and improvement in QoL. Age and duration of migraine were significant predictors of achieving a ≥ 50% reduction in headache frequency after therapy (OR = 0.955; p = 0.009) and (OR = 0.965; p = 0.025), respectively. Treatment compliance was observed in 76.2% of patients, and 24.5% discontinued treatment. Constipation was the most commonly reported AEs (6.0%), and conservative management was the most common approach to managing AEs. Conclusion Erenumab was effective in reducing the frequency and severity of migraine attacks and improving QoL, and safe with manageable AEs in a real-world setting in Kuwait. Further research is needed to better understand erenumab’s effectiveness and safety in different populations and settings, as well as to compare it with other migraine prophylactic treatments.

PACAP-38 and sex hormones in women with migraine: exploratory analysis of a cross-sectional, matched cohort study

BackgroundEndogeneous and exogeneous sex hormones can impact the frequency and severity of migraine attacks, but the underlying mechanisms are poorly understood. In this study, we investigate the relationship between female sex hormones and Pituitary Adenylate Cyclase-Activating Polypeptide-38 (PACAP-38) concentrations in plasma of women with migraine and healthy controls, aiming to elucidate potential hormonal influences on PACAP dynamics and their relevance to migraine pathophysiology.MethodsThis analysis is part of a cross-sectional, matched-cohort study. We recruited two groups of women with episodic migraine: one with a regular menstrual cycle (M-RMC) and another undergoing combined oral contraceptive treatment (M-COC). Additionally, we included corresponding age-matched control groups without migraine for both categories (C-RMC and C-COC). For participants with a RMC, the study visits were scheduled during the perimenstrual period (menstrual cycle day 2 ± 2) and periovulatory period (day 13 ± 2). Participants using COC were examined at day 4 ± 2 of the hormone-free interval and between day 7–14 of the hormone intake phase. During these visits, PACAP-38 concentrations in plasma were measured using a commercial Enzyme-linked-immunosorbent assay (ELISA) kit.ResultsThe study included 120 women, with 30 participants in each group. Women with migraine and a RMC had significantly higher PACAP-38 plasma concentrations compared to healthy controls at both study visits [day 2 ± 2: M-RMC: 2547.41 pg/ml (IQR 814.27 – 4473.48) vs. C-RMC: 1129.49 pg/ml (IQR 257.34 – 2684.88), p = 0.025; day 13 ± 2: M-RMC: 3098.89 pg/ml (IQR 1186.29 – 4379.47) vs. C-RMC: 1626.89 (IQR 383.83 – 3038.36), p = 0.028]. In contrast, PACAP-38 levels were comparable between migraine and control groups receiving COC. Women with migraine and a RMC exhibited higher PACAP-38 concentrations during menstruation compared to those using COC during the hormone-free interval.ConclusionSystemic PACAP-38 concentrations in women vary based on the presence of migraine diagnosis and their hormonal status.

P.006 Barriers and risk factors for emergency room visits vs smartphone app use for migraine in Canada and the United States

Background: Migraine affects more than 1 billion people, with attacks triggered by a variety of factors. Knowledge of environmental triggers for migraine attacks is limited, and has mostly been studied via emergency room (ER) visits. There are significant barriers and delays for attending ER for migraine treatment, which create challenges for estimating causal links to environmental exposures. We assessed whether smartphone app records may have fewer barriers and reduced lags. Methods: American and Canadian participants completed an online survey about their migraine attacks, smartphone app use, and ER visits. Results: Among 308 participants, barriers to visiting ER were similar in both countries, except for financial concerns in the US. About half of participants who attended ER also recorded the attack in a diary or app. Whereas migraine patients often present to ER 7+ days after onset, records in a smartphone app dataset were created within 2 days of onset. Conclusions: Although not all severe migraine attacks are recorded by smartphone users, smartphone app records may have fewer barriers to creation and shorter time lags compared to ER visit records, making them a rich source of data for research on transient neurologic health outcomes and environmental exposures.

Auricular Therapy for Migraine.

Migraine brings hours or even days of disability, affecting 15% of the US population and one billion people worldwide. Migraine treatments have improved over the years and there is now a range of non-pharmacologic therapies that can be administered as monotherapy, combined with pharmacologic therapy or combined with other non-pharmacologic therapies to give greater options for those who do not tolerate, do not respond to, or who wish to reduce or avoid pharmacologic treatments. We conducted a review of the literature on auricular therapy as acute or preventive treatment for migraine, searching the databases of MEDLINE and ClinicalTrials.gov from 2013 to 2023. A total of 43 articles contained at least one search term, with three studies specific to acute or prevention of migraine (one for acute only, one for prevention only and one for both acute and prevention). The population was limited to, adults with migraine ages 18 or older, with the administration of auricular therapy as the intervention. While there have been studies on the use of auricular therapy for pain on two specific standardized auricular therapies, Battlefield Acupuncture (BFA) and National Acupuncture Detoxification Association (NADA), neither of these protocols were utilized in any of the studies specific to migraine management. Each of the three studies used different techniques, with one using acupuncture needles and five specific points and two using semi-permanent needles (remained in for a few days) that were placed in areas that showed high activity. Each of these studies showed auricular therapy to have benefit for the management of migraine. However, the authors of each of the studies recommended further studies. Auricular therapy may be a helpful adjunctive treatment to abort a current migraine attack or aid in reducing the frequency or severity of migraine attacks.

The Effect of Melatonin on Reducing the Frequency and Severity of Migraine Attacks: A Double-Blind, Randomized Clinical Trial.

There is no definite recommendation for melatonin supplementation in episodic migraine. This study aimed to evaluate the effect of melatonin on reducing the frequency and severity of migraine attacks. This randomized, double-blind clinical trial was conducted at Golestan Hospital of Ahvaz, Iran, in 2021. A total of 60 patients with episodic migraine were randomly assigned into 2 groups of receiving 3 mg melatonin (intervention group; n=30) or the same dose of placebo (control group; n=30) along with baseline therapy (propranolol 20 mg, BID) for two months. The attack frequency, attack duration, attack severity (based on VAS), the number of analgesic intakes, drug complications, Migraine Disability Assessment score (MIDAS), and Pittsburgh sleep quality index (PSQI) were evaluated at baseline and in the first, second, third, and fourth months of follow-up. The independent t test, chi-square, and analysis of variance (ANOVA) with repeated measures were used to compare variables between the two groups. In both groups, the frequency, duration, and severity of attacks, taking analgesics, MIDAS, and PSQI scores during follow-up decreased significantly (P<0.001). After treatment, the mean frequency (P=0.032) and duration of attacks (P=0.001), taking analgesic (P<0.001), and MIDAS (P<0.001) and PSQI scores (P<0.001) in the melatonin group were lower than placebo. Only the attack severity was not significantly different between the two groups (P=0.126). Side effects were observed in two patients (6.7%) in the melatonin group and one patient (3.3%) in the placebo group (P>0.999). Our study shows that melatonin was more efficacious than the placebo in the reduction of frequency and duration of migraine attacks. It was equally safe as the placebo and might be effective in the preventive treatment of episodic migraine in adults.Trial Registration Number: IRCT20190107042264N5.

Study Protocol for Assessing the Effectiveness of Agomelatine on the Severity and Frequency of Episodic Migraine Attacks Without Aura: A Randomized Triple-Blind, Placebo-Controlled Trial

Background: Migraine is a chronic condition characterized by moderate to severe headache attacks, adversely affecting individual and social quality of life. Given the chronic nature of this disease, it is crucial to find medications that offer fewer side effects and enhanced effectiveness. Agomelatine, a synthetic analogue of the hormone melatonin, shares similar pharmacodynamics, such as stimulating melatonin receptors and inhibiting the 5HT2c receptor. Due to its favorable side-effect profile and high tolerability, agomelatine presents a viable alternative to traditional preventive treatments for migraines. Objectives: The primary objective of this trial is to evaluate the effectiveness of agomelatine in reducing the severity and frequency of episodic migraine attacks without aura. Methods: This study utilizes a parallel, triple-blind controlled trial design. Patients, aged between 18 and 60 years, who have been definitively diagnosed with episodic migraine without aura and have not received prior severity treatment, are eligible for this randomized controlled trial (RCT). A convenience sample of patients will be recruited from individuals visiting the clinic for migraine issues. If these individuals agree to participate and meet the inclusion criteria, they will be randomly assigned to either the intervention or control group using a random number table or software. The intervention group will receive 25 mg of agomelatine daily, while the control group will be given vitamin B1 as a placebo. Both the frequency and severity of migraine attacks will be monitored, along with the mean monthly migraine days (MMD) and migraine disability assessment (MIDAS) scores, before and after the intervention.

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

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

Efficacy of Nano-curcumin Supplementation on Depression, Anxiety, Stress and Clinical Symptoms in Migraine Patients: A Randomized Double-blind Clinical Trial

Background:: Migraine is a debilitating neuroinflammatory disorder. Patients with migraine often experience elevated levels of depression, anxiety, and stress, which are associated with the frequency and severity of migraine attacks. Curcumin has been shown to have regulatory effects on depression, anxiety, and stress, as well as analgesic properties through various mechanisms. The objective of this study was to assess the impact of nanocurcumin supplementation on depression, anxiety, stress, and clinical manifestations in patients with migraine. Methodology:: This study was conducted as a randomized, double-blind clinical trial. A total of forty-four patients with episodic migraines were recruited for the trial. Stratified randomization was employed to ensure a balanced distribution of participants based on BMI and sex. The patients were equally assigned to two groups using permuted block randomization: 1) the intervention group, which received 80 mg of nano-curcumin, and 2) the placebo (control) group, which received a paraffin-based placebo. The intervention and control periods lasted for 2 months. Anthropometric and demographic data, clinical signs and symptoms (including headache frequency, duration, and severity as reported by the patients), as well as stress, anxiety, and depression scores (using the Dass-21 questionnaire), were recorded before and after the study. The collected data were analyzed using SPSS 22. For normally distributed data, paired t-tests and independent t-tests were utilized. Non-normal data were analyzed using the Wilcoxon test and Mann-Whitney U test. The chi-squared test was employed for categorical variables. To account for confounding factors, the ANCOVA test was conducted. A p-value of ≤ 0.05 was considered statistically significant. The intention-to-treat method was applied to address outliers and missing data. Results:: Based on the findings, the current study demonstrates that supplementation with nano-curcumin can effectively mitigate symptoms of depression and anxiety (p &lt; 0.05). Regarding stress, a noticeable reduction within the nano-curcumin group was observed, although it did not reach statistical significance when compared between groups (p &gt; 0.05). Moreover, nano-curcumin exhibited a significant decrease in the frequency, duration, and severity of headaches (p &lt; 0.05). Conclusion:: Our research findings have shown that supplementation with nano-curcumin can effectively decrease the frequency, severity, and duration of headaches while also alleviating symptoms of depression and anxiety in comparison to the placebo group. Hence, curcumin exhibits significant potential as an adjuvant therapy to enhance the treatment of migraines.

The effect of simultaneous administration of occipital nerve block and cervical myofascial trigger point injection (MTrPI) on headache parameters in chronic migraine patients.

Peripheral myofascial mechanisms have been identified as contributors to migraine pathophysiology. The specific comorbid relationship between migraine and cervical trigger points may exacerbate the occurrence and severity of migraine attacks. Trigger point injections (TPIs) are frequently employed to address headaches and alleviate migraine symptoms. The current study explores the impact of concurrent myofascial trigger point injection (MTrPI) and occipital nerve block (greater occipital nerve block [GONB] + lesser occipital nerve block [LONB]) on the severity of headaches and the number of migraine attacks in individuals with chronic migraine (CM) and cervical myofascial trigger points (MTrPs), with a comparison of occipital nerve block alone (GONB + LONB). During trigger point examination and injection, trapezius, levator scapulae, splenius capitis, temporalis, and sternocleidomastoid muscles were targeted. We planned the treatment based on whether they were in the muscle groups we determined, rather than the number of trigger points. This study enrolled 62 individuals experiencing CM with bilateral headache and cervical MTrP who sought care at the Algology Unit within the Departments of Neurology and Physical Therapy and Rehabilitation at Siirt Training and Research Hospital between 2020 and 2022. The CM cohort was stratified into two groups: group 1 received trigger point injections (TrPI), while group 2 underwent concurrent bilateral occipital nerve block (GONB + LONB) and TrPI. Both groups underwent three treatment sessions with bupivacaine 0.5% (1ml = 5mg) in weeks 1, 2, and 4. Visual analog scale (VAS) was used to measure the patients' pain intensity. The evaluation included the assessment of the monthly migraine frequency and visual analog scale (VAS) p score for pain before treatment (BT) and after treatment (AT), conducted at baseline and during follow-up visits. Analysis of the data was conducted utilizing IBM SPSS Statistics for Windows version 28.0 software. Among patients diagnosed with CM and MTrPs, 32 individuals (51.6%) underwent GONB and LONB, while 30 patients (48.4%) received simultaneous GONB, LONB, and cervical MTrPI. Within the entire sample, 51 participants (82.3%) were female, and 11 (17.7%) were male, with a mean age of 32.81 ± 10.75years. With an average age of 32.81 ± 10.75years, there was no statistically significant variance between the two groups (p = 0.516). Of the total cohort, 45 individuals (72.6%) reported experiencing headaches persisting for 12months or longer. Among CM patients, 80% had active trigger points, while 20% had latent trigger points. No statistically significant difference was observed between the groups concerning TrPs (p = 0.158), and the distribution of TrPs was homogenous across the two groups. In group 1, the median (min-max) monthly frequency of migraines reduced from 18.5days (range: 15.0 to 25.0days) before treatment to 12.0days (range: 7.0 to 17.0days) after treatment (p = 0.000). In group 2, the median monthly frequency of migraines reduced from 16.5days (range: 15.0 to 22.0days) before treatment to 4.0days (range: 2.0 to 8.0days) after treatment (p = 0.000). The median (min-max) VAS score in group 1 was 8.0 (range: 5.0 to 9.0) before treatment, 4.0 (range: 2.0 to 6.0) at week 1, and 5.0 (range: 4.0 to 8.0) at week 4 (p = 0.000). In group 2, the median VAS score was 7.0 (range: 5.0 to 9.0) before treatment, 0.0 (range: 0.0 to 0.3) at week 1, and 2.0 (range: 0.0 to 0.3) at week 4 (p = 0.000). There were significant distinctions between the groups in terms of both the monthly count of migraine days and the severity of headaches (p = 0.000). The combination of repeated MTrPIs and ONB proves more effective than ONB alone in managing patients with CM and cervical MTrP. In patients with CM, performing TrPs examination and adding treatments for this may contribute to the treatment. In cases where patients endure prolonged episodes of headache associated with chronic migraine, the inclusion of trigger point injections alongside peripheral nerve blocks may offer enhanced therapeutic benefits.

Association between anemia severity and migraine in iron deficiency anemia.

Migraine is an episodic public health problem that usually occurs with a severe headache. Various mechanisms and outcomes have been reported between iron deficiency anemia (IDA) and migraine. We aimed to investigate the effect of the presence and severity of anemia and iron parameters on the frequency and severity of migraine attacks. The study included 104 patients with IDA and newly diagnosed migraine in the neurology outpatient clinic and 38 age and gender-matched controls with normal hemoglobin levels. Patients were divided into 3 subgroups (mild, moderate, and severe anemia) to determine a significant relationship between the severity of IDA and migraine attacks. All patients were asked validated questions with the Visual Analogue Scale (VAS), Headache Impact Test-6 (HIT-6), and the Hamilton Anxiety Rating Scale (HAM-A) face-to-face. In this study, 85.6% of the participants were female, and 22 (14.6%) of them were male. Thirty-two mild anemia patients' mean age was 36.6 ± 12.5, 41 with moderate anemia was 46 ± 14.2, and 31 with severe anemia patients' mean age was 48 ± 14.1. There was no significant difference between the subgroups in VAS, HIT-6 score, headache type, and headache frequency. Menstrual migraine is associated with low hemoglobin levels. A significant increase was found in VAS and HIT-6 scores with low ferritin levels. The presence and severity of anemia and iron deficiency do not affect the frequency and severity of migraine attacks in groups other than menstruation-related migraine. An inverse relationship was found between VAS, HIT-6, and ferritin levels. VAS was found to be more effective than HIT-6.

CGRP Antagonism and Ketogenic Diet in the Treatment of Migraine.

The study of migraine is based on the complexity of the pathology, both at the pathophysiological and epidemiological levels. Although it affects more than a billion people worldwide, it is often underestimated and underreported by patients. Migraine must not be confused with a simple headache; it is a serious and disabling disease that causes considerable limitations in the daily life of afflicted people, including social, work, and emotional effects. Therefore, it causes a daily state of suffering and discomfort. It is important to point out that this pathology not only has a decisive impact on the quality of life of those who suffer from it but also on their families and, more generally, on society as a whole. The clinical picture of migraine is complex, with debilitating unilateral or bilateral head pain, and is often associated with characteristic symptoms such as nausea, vomiting, photophobia, and phonophobia. Hormonal, environmental, psychological, dietary, or other factors can trigger it. The present review focuses on the analysis of the physiopathological and pharmacological aspects of migraine, up to the correct dietary approach, with specific nutritional interventions aimed at modulating the symptoms. Based on the symptoms that the patient experiences, targeted and specific therapy is chosen to reduce the frequency and severity of migraine attacks. Specifically, the role of calcitonin gene-related peptide (CGRP) in the pathogenesis of migraine is analyzed, along with the drugs that effectively target the corresponding receptor. Particularly, CGRP receptor antagonists (gepants) are very effective drugs in the treatment of migraine, given their high diffusion in the brain. Moreover, following a ketogenic diet for only one or two months has been demonstrated to reduce migraine attacks. In this review, we highlight the diverse facets of migraine, from its physiopathological and pharmacological aspects to prevention and therapy.

The Association Between CGRP Gene -624 T→C Polymorphism and Headache Severity in Turkish Migraine Patients

ABSTRACT Aim: This study aims to explore -624 T→C polymorphism on CGRP gene in migraine patients, and the relation between this polymorphism and migraine attacks. Materials and methods: The study registered a total of 101 migraine patients, 17 with aura and 84 without aura and 80 healthy volunteers. CGRP -624 T→C polymorphism in migraine patients and the control group was evaluated using PCR-RFLP method. Results: Although no significant difference could be found between genotype and allele frequencies of CGRP -624T→C polymorphism in the patient and control groups (p&gt;O.O5). In addition, a statistically significant positive correlation was established between the severity of headache and C allele of this gene in migraine patients (p&lt;0.05). Conclusion: The fact that C allele of CGRP gene is at a higher rate in those with severe migraine attacks suggests that this allele can render neuroinflammation more marked by increasing the amount of CGRP. However, how CGRP -624T→C polymorphism influences the expressian level of the gene is not known for sure yet.

Effectiveness of integrated education and relaxation program on migraine-related disability: a randomized controlled trial

BackgroundMigraine is one of the most disabling disorders worldwide. Globally, in 2019, headache disorders were the cause of 46.6 million years of disability, with migraine accounting for 88.2% of these. The value of integrative strategies in migraine management has been raised due to the recurrent and provoked nature of migraine. So, the current study aimed to evaluate the effectiveness of implementing a therapeutic patient education and relaxation training program versus usual pharmacological treatment alone on the frequency, severity, and duration of migraine attacks as the primary outcome and migraine-related disability and quality of life as the secondary outcome. A randomized controlled trial was conducted at the specialized headache clinic of a tertiary referral center. Sixty patients were randomly assigned to intervention or control groups. Participants in the intervention arm received the education and relaxation training program and were instructed to perform daily relaxation exercises in addition to their routine pharmacological treatment, whereas the control group only received their routine treatments. Follow-up was done after 1 and 3 months using a headache diary and a migraine-specific quality of life questionnaire (MSQ).ResultAfter implementation of the program, there was a significant reduction in migraine attack severity in the intervention group compared to the control group, and they also had significantly fewer migraine headache days/month and duration of migraine attacks compared to patients in the control group. Statistically significant improvement in the role-function restrictive, role-function preventive, and emotional function domains of MSQ.ConclusionAn integrated migraine management program has a significant effect on reducing the burden of migraine attacks and improving the daily activities of migraine sufferers.