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.

The role of vitamin D in the development and prevention of migraine: a review

Introduction and Purpose Migraine is a widespread neurological disorder characterized by severe, pulsating headaches often accompanied by nausea, vomiting, and hypersensitivity to light and sound. Although its exact cause is still under investigation, recent studies suggest that vitamin D deficiency may play a role in migraine occurrence and severity. Vitamin D, known primarily for its role in bone health, also affects the nervous and immune systems, and may influence inflammatory processes involved in migraine pathogenesis. This literature review aims to explore the relationship between vitamin D supplementation and the frequency and intensity of migraines, and whether supplementation could support migraine treatment. Material and Methods A comprehensive literature review was conducted using the PubMed database, focusing on articles published until the end of 2023. The search included the keywords: "vitamin D," "migraine," "headache," and "supplementation" in various combinations. Relevant studies were selected based on criteria such as monitoring vitamin D levels and the use of supplementation as an intervention in migraine patients. Results The results of the review suggest that vitamin D deficiency may be associated with an increased frequency of migraines. Supplementation with vitamin D was linked to a reduction in both the frequency and severity of migraines. While not all studies were consistent, the majority indicated that supplementation had a positive impact, particularly in individuals with vitamin D deficiency. Conclusions The findings suggest that vitamin D deficiency could be a risk factor for migraines, and that supplementation with vitamin D may help reduce the severity and frequency of migraine attacks. Although further research is required to establish optimal dosages and treatment protocols, vitamin D supplementation shows promise as a supportive therapy in migraine management.

Patterns, Barriers, and Preferences of Treating Migraine Within the School Setting: A Survey Study of Students

Background/Objectives: Migraine affects 10% of adolescents and children. Typical school protocols in the USA require pharmacological medications to be administered by school nurses, often resulting in treatment delays or omissions when migraine attacks occur during school hours. The Remote Electrical Neuromodulation (REN) wearable is an FDA-cleared smartphone-controlled device delivering acute and preventive treatment of migraine attacks in patients aged 8 and above, allowing safe, effective, discreet, and independent usage. Methods: This retrospective study (NCT06180577) evaluates treatment patterns, barriers, and preferences among school-age students. REN users < 18 years old were invited to complete an online survey. Participants signed an assent form, and their parents/legal guardians signed an informed consent form. Results: 332 patients aged 7–17 (15.5 ± 2.1) participated (80.4% female). After being prescribed the REN wearable, the percentage of students who treated their headaches at school increased from 78.3% to 89.8%. Most participants (65.4%) treated with either REN standalone (38.0%) or in combination with medications (27.4%). Common barriers to treatment included the need to leave class for the nurse’s office (64.2%), concerns about standing out (42.2%), and one barrier unique to REN–permission needed to use a smartphone in class (22.9%). The most common reasons given for preferring REN treatment at school are the ability to avoid going to the nurse’s office (42.5%) and to treat discreetly (39.2%). Conclusions: This study underscores the challenges of managing migraine at school while suggesting the importance of the REN wearable as a discreet and independently used first-line treatment for children and adolescents.

New insights into the increased risk of migraines from COVID-19 infection and vaccination: a Mendelian randomization study

IntroductionMigraine is a prevalent neurological disorder characterized by recurrent attacks, leading to a substantial global disease burden. Recent observational studies have reported the onset and worsening of migraine following COVID-19 infection and vaccination. However, traditional observational study designs have limitations in controlling for confounding factors, potentially resulting in biased and inconsistent conclusions. To address this, we applied Mendelian randomization (MR) to investigate the causal relationship between COVID-19 infection and vaccination with migraine.MethodsThis study utilized summary-level genome-wide association study (GWAS) data from the GWAS catalog and FinnGen database to evaluate the effects of varying degrees of COVID-19 infection and vaccination on migraine. We employed inverse variance weighted (IVW) fixed-effect and random-effect models as the primary methods for MR analysis, with MR-Egger and other approaches as complementary methods. Sensitivity analyses, including Cochran's Q test, MR-Egger intercept regression, and MR-PRESSO, were conducted to ensure robustness of the results.ResultsOur MR analysis revealed no significant causal association between COVID-19 infection and migraine. However, a significant causal association was found between COVID-19 vaccination and migraine (beta = 0.071, P = 0.034). The results were confirmed through a series of sensitivity tests, demonstrating the robustness of the findings.DiscussionThis study provides novel evidence of a significant causal link between COVID-19 vaccination and migraine, while no such association was observed with COVID-19 infection. These findings may have important implications for clinical practice, particularly in planning treatment adjustments and optimizing patient care for individuals with migraines in the context of COVID-19 vaccination.

Physical activity and supplementation as alternative methods in migraine prophylaxis -literature review

Migraine is a common and debilitating neurological disorder. It is crucial to realize that migraines are distinguished from other types of headaches. People suffering from migraine are often unable to function normally, neglecting work and daily duties. The associated costs burden not only the patients but also their family and social life. What is more, many psychiatric comorbidities are common in migraine patients. Because of all these factors, preventive treatment is essential because it can decrease migraine frequency and improve quality of life. There are many preventative medications but satisfactory improvement in reducing the frequency of migraine attacks may not be achieved without modification of lifestyle including taking care of physical activity and supplementation. Many studies have shown that moderate physical activity and supplementation of vitamins B2, D, coenzyme Q10 and magnesium has a positive effect on reducing duration and frequency of the migraine attack.

Is the combination of propranolol and flunarizine better than propranolol, flunarizine and amitriptyline alone in prophylaxis of migraine? An observational study at a tertiary care centre of North India

Background: Migraine is a primary headache disorder marked by recurrent attacks of pain and associated symptoms. Propranolol is traditionally considered highly effective for migraine prophylaxis, but other drugs have recently shown promise. Methods: This study was a prospective, observational, randomized, parallel-arm, unicentric trial conducted in the neurology department of a tertiary care hospital in North India. Patients with migraine without aura were randomly assigned to one of four treatment groups. After obtaining consent, patients were randomized using a random number table. Group 1 received propranolol (80 mg), group 2 received flunarizine (10 mg), group 3 received a combination of propranolol (40 mg) and flunarizine (10 mg), and group 4 received amitriptyline (10 mg) daily. The primary outcome was a change in the frequency of migraine days, while secondary outcomes included changes in moderate-to-severe headache days and disability levels. Results: The combination of propranolol (40 mg) and flunarizine (10 mg) was significantly more effective in reducing the frequency of migraine attacks at the end of 3 months compared to the group receiving amitriptyline (10 mg). However, no significant differences between the groups were observed at baseline, 1 month, and 2 months. For other outcomes, including adverse drug reactions (ADRs), there were no significant differences between the groups. Conclusions: The combination of propranolol (40 mg) and flunarizine (10 mg) demonstrated superior efficacy over amitriptyline (10 mg) after prolonged treatment, while its effectiveness was comparable to other groups at earlier time points. ADRs were similar across all groups.

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.

Analysis of migraine characteristics in postmenopausal women

Objective: to identify characteristics of migraine in women in postmenopause (PM) by analyzing the frequency, duration and intensity of migraine attacks, assessment of quality of life, anxiety, depression and sleep disturbances in patients in the reproductive phase (RP) and in the PM.Material and methods. The study comprised 60 migraine patients (30 patients in the RP, 30 patients in the PM). During the personal interview, age, migraine type, frequency and duration of attacks and headache (HA) intensity on the visual analogue scale (VAS) were recorded. The patients then completed the questionnaires: HIT-6, MIBS-4, HURT, Migraine- ACT, MIDAS, SF-36, HADS, ISQ. The statistical analysis was performed in Microsoft Office Excel 2021.Results. The risk of high intensity HA (≥8 points on the VAS) was significantly higher in patients in the PM than in patients in the RP [p<0.05; relative risk (RR) 1.77]. The risk of necessity of a revision of therapy of attacks was higher in the PM than in the RP (p=0.004; RR=2.2). The risk of insomnia was higher in the PM than in the RP (p=0.004; RR=4.67). The risk of severe headache impact (HIT-6) and high migraine burden (MIBS-4) was higher in patients in the PM than in the RP (ORHIT6=1.7; ORMIBS4=1.78). All indicators of SF-36 quality of life questionnaire were significantly lower in patients in the PM group than in the RP group (p<0.05). The risk of subclinical and clinical anxiety (p<0.05; RR=4.33) and depression (p<0.05; RR=2.75) was significantly higher in the PM than in the RP.Conclusion. Migraine attacks in women in the PM are more intense than in women in the RP, quality of life is lower, and revision of therapy for attacks is required more frequently. Patients with migraine in the PM are more likely to suffer from anxiety, depression and insomnia. Further research is needed to determine the causes of the observed phenomena and to develop migraine therapy in patients in the PM.

Migraine and epilepsy frontiers, new challenges in its understanding: A case report

The relationship between migraine and epilepsy has been recognized since the 20th century. Currently, both pathologies share several characteristics, from molecular and electrophysiological mechanisms to their similarity in clinical symptoms and response to treatment. This is a case report of an 11-year-old male patient who presented with focal epilepsy at the age of 8 years. One year later, he developed episodes of migraine without aura followed by seizures with a frequency of 1–2 times per month, with headache duration ranging from 10 min to 6 h. At age 11, he also presented other episodes in which the headache occurred after the epileptic event and other episodes in which the headache was present both before and after the epileptic seizure. An interictal EEG study and an EEG study during a migraine attack showed the presence of high-voltage theta activity and bilateral temporo-parieto-occipital spikes with a greater expression in the right cerebral hemisphere. To our knowledge, this is the first report of an atypical presentation of migraine without aura and epileptic seizure. This case opens new challenges in the search for understanding between both pathologies.

Gastric stasis in migraine and the efficacy of antimigraine drugs

Migraine is characterized by severe headache attacks with the development of accompanying symptoms. Among the most common are nausea and vomiting, which limit the intake of oral medications and thus reduce the speed of onset of pain relief and the efficacy of treatment in general. The development of gastric stasis in migraine is considered to be one of the most important reasons for the delayed absorption and inconsistent effect of oral triptans. The rapid action of triptans in the form of orally dispersible tablets, efficacy in relieving pain and accompanying symptoms, and ease of administration make this form favorable as a first-line agent for the relief of migraine attacks.

The potential to prevent unnecessary emergency department visits by timely diagnosis of migraine-A prospective observational study.

Successful acute migraine treatment potentially prevents emergency room (ER) consultations but requires that the diagnosis of migraine was given earlier. The aim of this study is to quantify the problem of missed migraine diagnosis prior to ER visits. Inclusion criterion for this single-center prospective study was the presentation at the ER for acute headache. Patients with acute migraine attacks were assessed for previous migraine attacks, and whether they were given a diagnosis of migraine in the past. Of 137 patients with migraine diagnosis at discharge, 108 (79%) had previous headache attacks fulfilling the criteria for migraine according to The International Classification of Headache Disorders 3rd edition (ICHD-3). Of those, 54 (50%) received the diagnosis for the first time. Half of the migraine patients (50%) presenting in the ER for headache could have been diagnosed earlier. This highlights the need for better detection and treatment of migraine by pre-hospital healthcare providers, as earlier diagnosis and specific acute treatment could have prevented the ER visit.

Effects of selected dietary supplements on migraine prophylaxis: A systematic review and dose-response meta-analysis of randomized controlled trials.

The existing evidence on the effect of dietary supplements for preventing migraines has generated conflicting results. We assessed alterations in migraine clinical features corresponding to the intake of dietary supplements. Our main outcomes included the frequency (number of attacks), duration (in hours), the severity (intensity) and the monthly migraine days. Using a dose-response meta-analysis, we estimated the dose-dependent impact. The certainty of evidence was evaluated using the GRADE tool. Finally, twenty-two trials were included in the systematic review and meta-analysis. Magnesium supplementation reduced migraine attacks (mean difference (MD) = -2.51), severity (MD = -0.88), and the monthly migraine days (MD = -1.66) compared with the control group. CoQ10 decreased the frequency (MD = -1.73), severity (MD = -1.35), and duration of migraine (MD = -1.72). Riboflavin decreased attack frequency (MD = -1.34). Alpha-lipoic acid decreased attack frequency (MD = -1.24) and severity (MD = -0.38). Probiotics decreased the frequency (MD = -1.16), severity (MD = -1.07) and the monthly migraine days (MD = -3.02). Vitamin D reduced migraine frequency (MD = -1.69) and the monthly migraine days (MD = -2.41). In adults, compared with placebo, these supplements did not significantly affect other outcomes, and omega-3 supplementation did not yield a statistically significant reduction in any of these outcomes. The use of certain dietary supplements has resulted in a significant decrease in migraine prophylaxis. Further clinical trials of high quality appear to be beneficial.

Preserved working memory performance along with subcortical modulation during peri-ictal phases in spontaneous migraine attacks.

To analyze cognitive performance and brain activation during a working memory task in patients with migraine during various phases of the migraine cycle and compare to healthy participants. Cognitive difficulties reported during migraine attacks remain poorly understood, despite evidence that the lateral frontoparietal network undergoes reversible disturbances and decreased activation during attacks. Recent findings in resting state functional magnetic resonance imaging suggest that brain areas involved in this network interact with subcortical regions during spontaneous migraine attacks. In this prospective, within-subject study, 10 patients with diagnosed menstrual-related episodic migraine without aura underwent 3T functional magnetic resonance imaging assessments while performing a working memory task across four phases of the natural migraine cycle: peri-ictal (preictal, ictal, postictal) phases and interictally (between attacks). Migraine prophylaxis was an exclusion criterion. Fourteen healthy controls were assessed during the corresponding phases of their menstrual cycles. The protocol was completed by 24 female participants aged 21 to 47 years: 10 with migraine (four sessions each) and 14 healthy controls (two sessions each) yielding a total of 68 analyzed datasets. Patients and controls showed similar performance on the working memory task and displayed increased brain activity in regions linked to this function, namely the middle frontal gyrus, inferior parietal lobe, and anterior cingulate cortex, during all phases of the migraine/menstrual cycle. Patients with migraine (N = 10) exhibited a significant decrease in hypothalamic activity (p = 0.007) as measured by the percent signal change (PSC) during the postictal phase compared to perimenstrual controls (N = 14), with -2 (16) and 31 (35) PSC, respectively. Comparing across the migraine cycle, the change in hypothalamic activity relative to controls in the postictal phase -0.33 (0.2) ΔPSC was significantly different from the ones in the interictal (0.006 [0.5] ΔPSC; p = 0.002) and preictal (-0.08 [0.4] ΔPSC; p = 0.034) phases. During a working memory task, cognition-related brain activation was present across all phases of the migraine cycle similarly to healthy control participants. Patients with migraine, however, displayed lower neural activity at the subcortical level in the postictal phase. Nonetheless, the sample size is a limitation for the generalization of our results. More research is needed to fully understand how the brain copes with cognitive demands during spontaneous migraine attacks.

Pediatric migraine is characterized by traits of ecological and metabolic dysbiosis and inflammation.

Recently, there has been increasing interest in the possible role of the gut microbiota (GM) in the onset of migraine. Our aim was to verify whether bacterial populations associated with intestinal dysbiosis are found in pediatric patients with migraine. We looked for which metabolic pathways, these bacteria were involved and whether they might be associated with gut inflammation and increased intestinal permeability. Patients aged between 6 and 17years were recruited. The GM profiling was performed by the 16S rRNA metataxonomics of faecal samples from 98 patients with migraine and 98 healthy subjects. Alpha and beta diversity analyses and multivariate and univariate analyses were applied to compare the gut microbiota profiles between the two group. To predict functional metabolic pathways, we used phylogenetic analysis of communities. The level of indican in urine was analyzed to investigate the presence of metabolic dysbiosis. To assess gut inflammation, increased intestinal permeability and the mucosal immune activation, we measured the plasmatic levels of lipopolysaccharide, occludin and IgA, respectively. The α-diversity analysis revealed a significant increase of bacterial richness in the migraine group. The β-diversity analysis showed significant differences between the two groups indicating gut dysbiosis in patients with migraine. Thirty-seven metabolic pathways were increased in the migraine group, which includes changes in tryptophan and phenylalanine metabolism. The presence of metabolic dysbiosis was confirmed by the increased level of indican in urine. Increased levels of plasmatic occludin and IgA indicated the presence of intestinal permeability and mucosal immune activation. The plasmatic LPS levels showed a low intestinal inflammation in patients with migraine. Pediatric patients with migraine present GM profiles different from healthy subjects, associated with metabolic pathways important in migraine.

Association between human herpes simplex virus and severe headache or migraine among aged 20-49 years: a cross-sectional study.

Previous studies have shown that human herpes simplex virus (HSV) infection may be associated with the onset of headache or migraine. We aimed to investigate the association between HSV infection and severe headache or migraine. The cross-sectional data on 5,730 participants aged 20-49 years were obtained from the 1999-2004 National Health and Nutrition Examination Survey (NHANES). We used weighted logistic regression analysis to assess the association between HSV infection (HSV-1 gG-1 and HSV-2 gG-2) and severe headache or migraine, and performed subgroup analyses. Our study found that women, higher education, higher body mass index, better family conditions, smoking and alcohol consumption were all associated with severe headaches or migraines. After adjusting for confounding factors such as sex, age, race, and education, HSV-2 (+) was still significantly associated with severe headache or migraine (OR = 1.22, 95%CI:1.03-1.46, p = 0.0443). In subgroup analyses, we found that participants with HSV-1 (-) and HSV-2 (+) were also significantly associated with severe headache or migraine (OR = 1.41, 95%CI:1.04-1.91, p = 0.0281). HSV-2 gG-2(+) was significantly associated with severe headache or migraine.

Long-Term (12-Month) Safety and Tolerability of STS101 (Dihydroergotamine Nasal Powder) in the Acute Treatment of Migraine: Data from the Phase 3 Open-Label ASCEND Study.

STS101 is an investigational drug-device combination comprising 5.2 mg dihydroergotamine (DHE) powder (6.0 mg DHE mesylate) in a single-use nasal delivery device for the acute treatment of migraine. The primary objective of the ASCEND trial was to assess long-term safety and tolerability of STS101 in the acute treatment of migraine attacks across 12-18 months, with secondary objectives describing efficacy. ASCEND was an open-label study of STS101 in adults aged 18-65 years with a ≥ 1 year history of migraine with or without aura, with onset before the age of 50 years and 4-12 migraine attacks/month and < 15 headache days/month in each of the 3 months prior to screening. Exclusion criteria included diagnosis of non-migraine headache, history of cerebrovascular disease, and ≥ 2 cardiovascular risk factors. After establishing eligibility, participants could self-administer STS101 5.2 mg as needed for up to 2 doses within 24 h to treat a single migraine attack and up to 12 doses/month. Safety and tolerability evaluations included physical and nasal examinations, vital signs, laboratory tests, and treatment-emergent adverse event (TEAE) assessments. Participants used an electronic diary to record exploratory efficacy parameters, including intensity of headache pain and associated migraine symptoms (photophobia, phonophobia, and nausea). Participant impression questions were asked at months 3, 6, and 12. Of the 6610 migraine attacks treated with a total of 8234 STS101 doses in 344 participants, 945/6610 (14.3%) were associated with a TEAE. Events were predominantly mild or moderate in nature and rarely led to premature study discontinuation (15/344 [4.4%] participants). Treatment was associated with rapid onset of freedom from pain (36.6%, 67.1%, and 85.5% of treated attacks 2, 4, and 24 h post-dose, respectively), freedom from most bothersome symptoms (54.3%, 79.6%, and 91.3%), and headache relief (66.5%, 89.1%, and 94.3%). Most participants rated treatment results as good or very good and ease of use as easy or very easy at all time points (months 3, 6, and 12) and indicated they were likely or very likely to use STS101 again. The repeated long-term, as-needed use of STS101 was well tolerated, demonstrating a favorable safety profile in the acute treatment of migraine attacks in appropriately indicated adults. Exploratory efficacy evaluations indicated beneficial effects, which warrant further evaluation. ClinicalTrials.gov identification NCT04406649.

Sustainable chemometric analysis of tension headache drugs in the presence of nephrotoxic impurities

A three-drug combination of caffeine, aspirin and paracetamol is widely prescribed as a first-line treatment for tension headaches and migraine attacks. Being of easy access as an over-the-counter medication, renal papillary necrosis may be caused if large doses are taken chronically. Moreover, several toxic impurities such as p-aminophenol and p-hydroxy acetophenone may be formed during the synthesis or storage of paracetamol. These impurities are classified as nephrotoxic and teratogenic materials which obliges pharmaceutical companies to develop cost-effective methodologies for their detection along with paracetamol itself. During the current study, multivariate chemometric-assisted spectrophotometric models namely; Partial Least Squares, Genetic Algorithm-Partial Least Squares and Multivariate Curve Resolution-Alternating Least Squares were developed for assaying and resolving the complex spectral overlap of the ternary combination in the presence of the nephrotoxic impurities; p-aminophenol and p-hydroxy acetophenone. A comparison was held between the three models where the optimized Genetic Algorithm-Partial Least Squares and Multivariate Curve Resolution-Alternating Least Squares models reduced the root mean square by 18.1%, 21.7%, 20.0%, 43.9% and 11.5% and 31.5%, 32.6%, 39.3%, 54.6% and 37.9% for caffeine, aspirin, paracetamol, p-aminophenol and p-hydroxy acetophenone, respectively. Panadol® migraine tablets were successfully analyzed using the constructed models without interference from the excipients. A statistical comparative analysis and greenness evaluation were carried out using two assessment tools including the “Green Analytical Procedure Index” and the “Analytical Greenness metric”. Also, the “Whiteness Analytical Chemistry tool” using the RGB12 model and the Blueness Applicability Grade Index were applied. Greener quadrants and a high score of 0.74 for the greenness tools were achieved with accepted statistical parameters regarding t and f values. Also, the high scores of the Blueness Applicability Grade Index and RGB12 metrics of 90 and 98.3, respectively confirmed the method's wide practicality and utility. Although other chemometric methods were reported for assaying the ternary combination, our developed method was the only one that incorporated toxic impurities during the analysis along with implementing greenness, whiteness and blueness assessments to ensure the method's sustainability.

Phasic perfusion dynamics among migraine subtypes: a multimodel arterial spin labeling investigation

BackgroundMigraine-related perfusion changes are documented but inconsistent across studies due to limited sample size and insufficient phenotyping. The phasic and spatial dynamics across migraine subtypes remains poorly characterized. This study aimed to determine spatiotemporal dynamics of gray matter (GM) perfusion in migraine.MethodsWe prospectively recruited episodic (EM) and chronic migraine (CM) patients, diagnosed with the International Headache Society criteria and healthy controls (HCs) between 2021 and 2023 from the headache center in a tertiary medical center, and adjacent communities. Magnetic resonance (3-tesla) arterial spin labeling (ASL) was conducted for whole brain cerebral blood flow (CBF) in all participants. The voxel-wise and whole brain gray matter (GM) CBF were compared between subgroups. Spatial pattern analysis of CBF and its correlations with headache frequency were investigated regarding different migraine phases and subtypes. Sex- and age-adjusted voxel-wise and whole brain GM comparisons were performed between HCs and different EM and CM phases. Spatial pattern analysis was conducted by CBF clusters with phasic differences and spin permutation test. Correlations between headache frequency and CBF were investigated regarding different EM and CM phases.ResultsTotally 344 subjects (172 EM, 120 CM, and 52 HCs) were enrolled. Higher CBF in different anatomical locations was identified in ictal EM and CM. The combined panels of the specific locations with altered CBF in ictal EM on receiver operating characteristic curve analysis demonstrated areas under curve of 0.780 (vs. HCs) and 0.811 (vs. preictal EM). The spatial distribution of ictal-interictal CBF alteration of EM and CM were not correlated with each other (p = 0.665; r = − 0.018). Positive correlations between headache frequency and CBF were noted in ictal EM and CM regarding whole GM and specific anatomical locations.ConclusionsPatients with migraine exhibited unique spatiotemporal CBF dynamics across different phases and distinct between subtypes. The findings provide neurobiological insights into how selected anatomical structures engage in a migraine attack and adapt to plastic change of repeated attacks along with chronicity.

Migraine in antiphospholipid syndrome and hereditary thrombophilia: pregnancy-related clinical and diagnostic features and therapeutic issues

Introduction. Migraine is one of the most common primary headaches and a risk factor for cardiovascular and cerebrovascular diseases. Antiphospholipid syndrome (APS) and hereditary thrombophilia (HT) causing pathological pregnancy are highly associated with migraine. Timely migraine recognition related to APS and HT facilitates earlier initiation of thrombophilia pathogenetic therapy and prevention of potential complications.Aim: to analyze the literature data on migraine clinical and diagnostic features in APS and HT as well as pregnancy-related therapeutic issues.Materials and Methods. A search for scientific literature was conducted in electronic databases including PubMed, Google Scholar, eLibrary from 2004 until May 2024. The search methodological basis included the presence of the following keywords and their combinations in Russian and English: "migraine", "antiphospholipid syndrome", "thrombophilia", "migraine and pregnancy", "migraine and thrombophilia", "migraine and cardiovascular diseases". As a result, a total of 184 publications were identified. Next, 62 articles were included in the review.Results. At the current stage, neurologists have no means to diagnose migraine in APS and HT based on headache-intrinsic characteristics. Pregnancy increases a risk of thrombotic complications. A migraine observed in patient's history should be crucial while assessing pregnancy-related obstetric risk. While diagnosing migraine, neurologists need to examine patient obstetric history. The data on most effective and safe therapy for pregnancy-related migraine attacks remain scarce.Conclusion. The frequent association between APS and HT with migraine, the lack of clear migraine clinical features in thrombophilia, patients’ reproductive age, and the high risk of thrombotic complications necessitate collaboration between neurologists and obstetricians-gynecologists for timely diagnostics and management of such patients. The impact of various types of antithrombotic therapy on migraine course requires further clarification. It is promising to conduct studies able to determine of whether migraine attack prevention can avoid adverse pregnancy outcomes in women with former migraine.

The Clinical Concurrence of Migraine and Transient Global Amnesia: Case Series of ‘Migramnesia’?

ABSTRACTComplaint of transient impairment or loss of memory as an attendant feature in some migraine attacks has long been recognised. In some cases, migraine may be a trigger or precipitating factor for the syndrome of transient global amnesia (TGA); however, the exact frequency of this concurrence is unknown. Here, the authors present three cases of TGA in the context of migraine headache, consider possible reasons why this concurrence might be under‐recognised, review possible shared pathogenetic mechanisms and suggest a new terminology—‘migramnesia’—which may encourage clinicians to address the possible significance of migraine in the context of an episode of TGA.