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Frontiers in Molecular Neuroscience 2024To assess the potential of ferroptosis and ferritinophagy in migraine pathogenesis. (Review)
Review
OBJECTIVE
To assess the potential of ferroptosis and ferritinophagy in migraine pathogenesis.
BACKGROUND
Ferroptosis and ferritinophagy are related to increased cellular iron concentration and have been associated with the pathogenesis of several neurological disorders, but their potential in migraine pathogenesis has not been explored. Increased iron deposits in some deep brain areas, mainly periaqueductal gray (PAG), are reported in migraine and they have been associated with the disease severity and chronification as well as poor response to antimigraine drugs.
RESULTS
Iron deposits may interfere with antinociceptive signaling in the neuronal network in the brain areas affected by migraine, but their mechanistic role is unclear. Independently of the location, increased iron concentration may be related to ferroptosis and ferritinophagy in the cell. Therefore, both phenomena may be related to increased iron deposits in migraine. It is unclear whether these deposits are the reason, consequence, or just a correlate of migraine. Still, due to migraine-related elevated levels of iron, which is a prerequisite of ferroptosis and ferritinophagy, the potential of both phenomena in migraine should be explored. If the iron deposits matter in migraine pathogenesis, they should be mechanically linked with the clinical picture of the disease. As iron is an exogenous essential trace element, it is provided to the human body solely with diet or supplements. Therefore, exploring the role of iron in migraine pathogenesis may help to determine the potential role of iron-rich/poor dietary products as migraine triggers or relievers.
CONCLUSION
Ferroptosis and ferritinophagy may be related to migraine pathogenesis through iron deposits in the deep areas of the brain.
PubMed: 38915936
DOI: 10.3389/fnmol.2024.1427815 -
Frontiers in Neurology 2024Women can experience various reproductive events, such as pregnancy, childbirth, lactation, and contraception, which cause long-term changes in female hormones. In...
The influence of factors associated with past reproductive histories on migraines in middle-aged premenopausal women: a nationwide population-based study in Republic of Korea.
INTRODUCTION
Women can experience various reproductive events, such as pregnancy, childbirth, lactation, and contraception, which cause long-term changes in female hormones. In middle-aged women, the prevalence of migraine is high, and a clear gender difference is evident. This study investigated the effects of factors associated with past reproductive events on the risk of new migraine in middle-aged premenopausal women.
METHODS
The influence of reproductive factors on migraine in middle-aged women was investigated using the Korean National Health Insurance Service (KNHIS) and Korean Health Examination (KHE) databases. The reproductive factors of interest were parity, breastfeeding, and oral contraceptive (OC) use. The study included 949,704 middle-aged premenopausal women 40-60 years of age. The study population was divided into two groups based on new diagnosis of migraine during the follow-up period (2009-2018).
RESULTS
The risk of new migraine tended to increase in the primiparous (hazard ratio, HR: 1.179; 95% confidence interval, CI: 1.137-1.221) and multiparous groups (HR: 1.181; 95% CI: 1.142-1.221) compared with the nulliparous group. The breastfeeding ≥12 months group (HR: 1.071; 95% CI: 1.052-1.091) showed a significantly increased risk of new migraine compared with the non-breastfeeding group. All women in the OC groups (< 1 year, HR: 1.048; 95% CI: 1.028-1.069 and ≥ 1 year, HR: 1.100; 95% CI: 1.067-1.134) showed a higher risk of new migraine than those in the non-OC group.
CONCLUSION
The results of the current study indicate that childbirth, longer breastfeeding, and OC use may be associated with a higher risk of new migraine in middle-aged premenopausal women.
PubMed: 38915802
DOI: 10.3389/fneur.2024.1406443 -
BMC Neurology Jun 2024Chronic migraine (CM) is the most severe and burdensome subtype of migraine. Fremanezumab is a monoclonal antibody that targets the calcitonin gene-related peptide...
BACKGROUND
Chronic migraine (CM) is the most severe and burdensome subtype of migraine. Fremanezumab is a monoclonal antibody that targets the calcitonin gene-related peptide pathway as a migraine preventive therapy. This study aimed to conduct a cost-effectiveness analysis of fremanezumab from a societal perspective in the Netherlands, using a Markov cohort simulation model.
METHODS
The base-case cost-effectiveness analysis adhered to the Netherlands Authority guidelines. Fremanezumab was compared with best supportive care (BSC; acute migraine treatment only) in patients with CM and an inadequate response to topiramate or valproate and onabotulinumtoxinA (Dutch patient group [DPG]). A supportive analysis was conducted in the broader group of CM patients with prior inadequate response to 2-4 different classes of migraine preventive treatments. One-way sensitivity, probabilistic sensitivity, and scenario analyses were conducted.
RESULTS
Over a lifetime horizon, fremanezumab is cost saving compared with BSC in the DPG (saving of €2514 per patient) and led to an increase of 1.45 quality-adjusted life-years (QALYs). In the broader supportive analysis, fremanezumab was cost effective compared with BSC, with an incremental cost-effectiveness ratio of €2547/QALY gained. Fremanezumab remained cost effective in all sensitivity and scenario analyses.
CONCLUSION
In comparison to BSC, fremanezumab is cost saving in the DPG and cost effective in the broader population.
Topics: Humans; Migraine Disorders; Cost-Benefit Analysis; Netherlands; Antibodies, Monoclonal; Chronic Disease; Markov Chains; Female; Quality-Adjusted Life Years; Male; Cost-Effectiveness Analysis
PubMed: 38914929
DOI: 10.1186/s12883-024-03697-x -
International Medical Case Reports... 2024Although rare, cerebral venous sinus thrombosis (CVT) can result in significant neurological complications, particularly after childbirth. Early diagnosis poses a...
BACKGROUND
Although rare, cerebral venous sinus thrombosis (CVT) can result in significant neurological complications, particularly after childbirth. Early diagnosis poses a challenge due to symptom overlap with other conditions. Limited publications and underdiagnosis of CVT are prevalent in developing nations, notably in Ethiopia.
CASE
A 29-year-old mother, having given birth four times, presented to the emergency department in her second month postpartum with complaints of persistent headaches and blurred vision over three weeks. Additionally, she reported sudden weakness on her right side for one day. Despite previous treatments for migraine headaches, she was diagnosed with CVT after magnetic resonance imaging/venography revealed blockage in the right anastomotic vein and the posterior segment of the superior sagittal sinus. Treatment commenced with the anticoagulant enoxaparin. During hospitalization, she experienced one episode of generalized seizures, leading to transfer to the intensive care unit where phenytoin was added. Subsequent diagnosis of papilledema occurred. After a 16-day hospital stay, she was discharged with warfarin, phenytoin, and acetazolamide. Oral anticoagulation and other medications ceased after six months of treatment, considering the postpartum period as a temporary risk factor for CVT. The patient currently maintains good health and has resumed normal activities.
CONCLUSION
Maintaining a high index of suspicion for CVT during the postpartum period and promptly conducting imaging scans are crucial for early diagnosis. This approach can halt neurological decline and facilitate immediate recovery through early therapeutic interventions.
PubMed: 38911608
DOI: 10.2147/IMCRJ.S457170 -
Frontiers in Human Neuroscience 2024Brain fog is associated with significant morbidity and reduced productivity and gained increasing attention after COVID-19. However, this subjective state has not been...
IMPORTANCE
Brain fog is associated with significant morbidity and reduced productivity and gained increasing attention after COVID-19. However, this subjective state has not been systematically characterised.
OBJECTIVE
To characterise self-reported brain fog.
DESIGN
We systematically studied the cross-sectional associations between 29 variables with the presence of "brain fog." The variables were grouped into four categories: demographics, symptoms and functional impairments, comorbidities and potential risk factors (including lifestyle factors), and cognitive score. Univariate methods determined the correlates of brain fog, with long-COVID and non-long-COVID subgroups. XGBoost machine learning model retrospectively characterised subjective brain fog. Bonferroni-corrected statistical significance was set at 5%.
SETTING
Digital application for remote data collection.
PARTICIPANTS
25,796 individuals over the age of 18 who downloaded and completed the application.
RESULTS
7,280 of 25,796 individuals (28.2%) reported experiencing brain fog, who were generally older (mean brain fog 35.7 ± 11.9 years vs. 32.8 ± 11.6 years, < 0.0001) and more likely to be female (OR = 1.2, < 0.001). Associated symptoms and functional impairments included d (OR = 3.3), (OR = 1.6), (OR = 1.2, all < 0.0001), (OR = 2.2), (OR = 1.9), and performing (ORs = 1.8, all < 0.0001). Comorbidities included long-COVID-19 (OR = 3.8, < 0.0001), concussions (OR = 2.4, < 0.0001), and higher migraine disability assessment scores (MIDAS) (+34.1%, all < 0.0001). Cognitive scores were marginally lower with brain fog (-0.1 std., < 0.001). XGBoost achieved a training accuracy of 85% with cross-validated accuracy of 74%, and the features most predictive of brain fog in the model were difficulty focusing and following conversations, long-COVID, and severity of migraines.
CONCLUSIONS AND RELEVANCE
This is the largest study characterising subjective brain fog as an impairment of concentration associated with functional impairments in activities of daily living. Brain fog was particularly associated with a history of long-COVID-19, migraines, concussion, and with 0.1 standard deviations lower cognitive scores, especially on modified Stroop testing, suggesting impairments in the ability to inhibit cognitive interference. Further prospective studies in unselected brain fog sufferers should explore the full spectrum of brain fog symptoms to differentiate it from its associated conditions.
PubMed: 38911226
DOI: 10.3389/fnhum.2024.1409250 -
Clinical Case Reports Jun 2024Basilar artery fenestration should be considered in migraine patients, especially with a cerebrovascular family history, necessitating annual magnetic resonance...
Basilar artery fenestration should be considered in migraine patients, especially with a cerebrovascular family history, necessitating annual magnetic resonance imaging/angiography (MRI/MRA) monitoring and careful assessment of birth control regimens to mitigate risks.
PubMed: 38910835
DOI: 10.1002/ccr3.9107 -
Cureus May 2024Migraine is characterized by recurrent episodes of unilateral, pulsating headaches. At the cerebral and ocular levels, it is recognized that the vascular narrowing and...
BACKGROUND
Migraine is characterized by recurrent episodes of unilateral, pulsating headaches. At the cerebral and ocular levels, it is recognized that the vascular narrowing and loss of blood flow are transient; however, the chronic nature of migraine may result in long-term functional and structural changes in these structures. It could result in axonal loss and an alteration in the thickness of the retinal nerve fiber layers (RNFL). This study aimed to measure the RNFL thickness, which provides a useful indication of the state of the axons and the loss of ganglion cells in migraine patients, and to find out if RNFL thickness and the clinical features of migraine are correlated.
MATERIALS AND METHODS
Sixty patients with migraine and 60 age-gender-matched controls were recruited. A complete neurological and ophthalmological examination was performed, and spectral-domain optical coherence tomography (SD-OCT) was done to measure RNFL.
RESULTS
All quadrants of the retina on both sides showed non-statistically significant differences in RNFL thickness between migraine patients and controls (p-value >0.05). Furthermore, in all retinal quadrants on both sides, there was no statistically significant difference in RNFL thickness between migraine patients with aura and those without aura (p-value >0.05). Significant correlations were found between the duration of migraine disease and the superior RNFL thickness of both eyes, as well as the inferior RNFL in the right eye. There was also a significant correlation between the headache attack duration and RNFL thickness of the superior retina (p<0.05), Conclusion: Our key finding was that when comparing migraine patients to controls, RNFL thickness did not significantly change; however, the duration of migraine disease did significantly affect RNFL thickness.
PubMed: 38910687
DOI: 10.7759/cureus.60909 -
Cureus May 2024Ischemic strokes (IS) in young adults often evade early detection, resulting in delayed diagnosis until complications arise. Cervical/vertebral artery dissection, a... (Review)
Review
Exploring the Nexus: A Systematic Review on the Interplay of the Methylenetetrahydrofolate Reductase (MTHFR) Gene C677T Genotype, Hyperhomocysteinemia, and Spontaneous Cervical/Vertebral Artery Dissection in Young Adults.
Ischemic strokes (IS) in young adults often evade early detection, resulting in delayed diagnosis until complications arise. Cervical/vertebral artery dissection, a significant contributor to these strokes, presents with symptoms such as migraine with aura, severe headache, and neck pain, commonly overlooked due to their nonspecific nature. This review investigates early indicators of artery dissections, emphasizing their importance in diagnosis and exploring the correlation between methylenetetrahydrofolate reductase (MTHFR) gene C677T genotype polymorphism, hyperhomocysteinemia (HHCY), and IS in young adults. This systematic review encompasses a thorough analysis of 11 papers, including four observational studies, three case reports, three narrative reviews, and one experimental study, involving 4,840 patients aged 18-45 years. Findings reveal HHCY as a significant contributor to vascular damage and tissue ischemia leading to IS. The MTHFR gene C677T genotype polymorphism is closely associated with HHCY, often contributing to underdiagnosed strokes in young adults. Cervical/vertebral artery dissection may manifest as initial symptoms of neck pain or headache, remaining undiagnosed until imaging is conducted. Importantly, the review suggests that MTHFR gene polymorphism can be mitigated through simple supplementation with vitamin B12 and folates, serving as a valuable tool for primary prevention. Additionally, betaine, a methyl donor, was explored in severe MTHFR gene polymorphism cases resistant to conventional supplementation. In conclusion, recognizing the significance of early signs and symptoms, along with a high clinical suspicion, is crucial for preventing catastrophic outcomes, mortality, and morbidity associated with IS in young adults lacking traditional risk factors. The MTHFR gene C677T genotype polymorphism, a potential genetic cause, can be easily managed with simple measures but is often overlooked or underdiagnosed.
PubMed: 38910639
DOI: 10.7759/cureus.60878 -
Annals of General Psychiatry Jun 2024Migraine has been associated with mental disorders, however whether parental migraine is associated with an increased risk of major mental disorders (MMDs) in offspring...
BACKGROUND
Migraine has been associated with mental disorders, however whether parental migraine is associated with an increased risk of major mental disorders (MMDs) in offspring has not been investigated. We aimed to examine the risk of the development of MMDs in the offspring of parents with migraine compared with those of parents without migraine.
METHODS
This study used data derived from the Taiwan National Health Insurance Research Database. Offspring of parents with migraine and a control group consisting of offspring of parents without migraine matched for demographic and parental mental disorders were included. Cox regression was used to estimate the risk of MMDs, including schizophrenia, depressive disorder, bipolar disorder, autistic spectrum disorder (ASD), and attention deficit/hyperactivity disorder (ADHD). Sub-analyses stratified by the fathers and mothers were further performed to separately clarify the risks of MMDs among the offspring.
RESULTS
We included 22,747 offspring of parents with migraine and 227,470 offspring of parents without migraine as the controls. Parental migraine was significantly associated with an increased risk of ADHD (reported as hazard ratios with 95% confidence intervals: 1.37, 1.25-1.50), bipolar disorder (1.35, 1.06-1.71), and depressive disorder (1.33, 1.21-1.47) compared to the offspring of parents without migraine. Importantly, sub-analyses showed that only maternal migraine was significantly associated with these risks.
CONCLUSIONS
Due to the heavy burden of MMDs, healthcare workers should be aware of the risk of MMDs in the offspring of parents with migraine, particular in mothers.
PubMed: 38909222
DOI: 10.1186/s12991-024-00508-y -
PloS One 2024This study aims to assess the knowledge and perceptions of the public toward migraine in Saudi Arabia.
OBJECTIVE
This study aims to assess the knowledge and perceptions of the public toward migraine in Saudi Arabia.
METHODS
This cross-sectional survey assessed the knowledge and perceptions of migraine among Saudi Arabian individuals. The study was conducted over three months in 2023 (1st of June 2023 to 31st of August 2023) using a prevalidated online questionnaire divided into four sections.
RESULTS
A total of 1,975 adults aged between 18 and 64 completed the web-based survey. Of these, over half were male (n = 1,268; 64.2%). The main causes of migraine identified by the participants were genetic disease (n = 540, 27.3%), followed by physical disease (n = 341, 17.3%), head trauma (n = 274, 13.9%), and psychiatric disease (n = 157, 7.9%). The main symptoms identified by the participants were photophobia (21%), followed by inability to control urine (14.1%), vomiting and nausea (13.8%), and vision loss (8.3%). The majority of the participants in this study had a good knowledge of migraines, while 49% had poor knowledge. The migraine knowledge score was significantly associated with the participants' gender (p = 0.002), age (p = 0.0001), educational level (p = 0.001), employment status (p = 0.001), monthly income (p = 0.0001), region (p = 0.0001), and history of migraine (p = 0.0001).
CONCLUSION
Although one-third of the participants exhibiting good knowledge, deficiencies existed in certain clinical aspects, emphasizing the need for targeted educational interventions to enhance public awareness and understanding of migraines.
Topics: Humans; Male; Saudi Arabia; Adult; Migraine Disorders; Female; Cross-Sectional Studies; Health Knowledge, Attitudes, Practice; Middle Aged; Adolescent; Young Adult; Surveys and Questionnaires
PubMed: 38905175
DOI: 10.1371/journal.pone.0304840