Role of TNF-α in the Pathogenesis of Migraine.

Background: Neurogenic neuroinflammation has a wide role in migraine pathogenesis including the transition from episodic migraine to chronic one. The seed molecule of neurogenic neuroinflammation, i.e., the TNF-α proinflammatory molecule, has gathered a lot of attention. This pleiotropic cytokine is a classical component of inflammatory soup, secreted by the microglial cell, and promotes a wide range of inflammatory reactions. Aim: In this review, we aimed to provide a culminating and comprehending glimpse into the TNF-α in association with the migraine. Method: A systematic literature survey method with a mixture of keywords was utilized to grasp the different elements that represent the association between TNF-α and migraine. Discussion. Highlighted the probable involvement of the TNF-α with migraine, the complexity of the matter such as activation of NF-KB signaling cascade, autoactivation, sensitization, and increased likelihood of transition cannot be neglected. Being TNF-α as a core node, it becomes the factor for linking diseases such as chronic inflammatory disorders, including COVID-19, and also interaction with other genes to develop severe conditions. Conclusion: To this end, TNF-α plays a critical role in chronification, and inhibiting its signaling would likely be a crucial strategy for migraine therapy.

Comprehensive analysis of genes associated with migraine in the Indian population: a meta-analysis of genetic association studies with trial sequential analysis.

Migraine is a complex disorder with multigenic inheritance and is characterized by the cardinal symptom of unilateral headache. Many genes are responsible for increasing the susceptibility of disease within different populations. Therefore, our primary aim in this review was to catalog the many genes that have been studied in India and after collecting the necessary information, we calculated a more precise risk relationship between an identified variation and migraine. The gene and its associated risk variant were discovered in the Indian population using a PRISMA-based systematic literature review guideline from online databases such as PubMed & Google Scholar. We constructed pooled odds ratios with 95% confidence intervals using multiple genetic models. Also, we looked for heterogeneity using Cochran's Q Test and the I2 statistic. Publication bias was analyzed using Begg's and Egger's tests. A p-value less than 0.05 was judged to be statistically significant for all tests. After a critical analysis, a total of 24 studies explored about 21 genes with 31 variants out of which only nine genes have been studied more than two times in the Indian population and thus were found eligible for the meta-analysis. It has been found, that the ACE-DD variant (allele model: OR: 1.37 [1.11-1.69], I2 = 0%/ fixed model), ESR1-PvuII (allele model: OR: 1.47 [1.24-1.74], I2 = 0%/ fixed model) significantly increases the risk of migraine in Indian population. Also, a protective role of the LRP1-rs11172113variant was observed for both migraine and its clinical subtype i.e., MA (allelic model: OR of 0.65 [0.50-0.83] I2 = 44% and allele: OR: 0.54 [0.37-0.78], I2 = 52%) respectively. Overall, the results of this meta-analysis indicated that the ACE-DD variant and the ESR1-PvuII were associated with an increased risk of migraine in the Indian community, while the LRP1-rs11172113 variant was associated with protection from migraine in this population.

A Comprehensive Investigation of Risk Association Between the -786 T > C, + 884 G > A, VNTR, rs743506, rs3918226 of eNOS and Susceptibility of Migraine: A Updated Meta-Analysis Utilizing Trial Sequential Analysis.

With a feature of complex pathogenic mechanisms, migraine is a well-known common neurovascular disorder. Multiple genes are responsible for hindering the susceptibility of pain threshold one of which is the eNOS gene and its variants. Multiple independent observational studies with case-control design produced conflicting findings, which can be attributed to a variety of factors including varying sample sizes, demographic stratification, technique application, etc. Therefore, in the present study we aimed to find out the precise risk between the selected variant of eNOS and the risk of migraine and its clinical subtypes using a meta-analysis approach. To find the association between the risk variants of the eNOS gene and migraine, a PRISMA-based systematic literature review strategy was utilized to search via online resources including PubMed and Google Scholar. Using several genetic models, odds ratios with 95% confidence intervals were computed to pool the data. To access heterogeneity, Cochran's Q Test and I2 statistics were utilized, while Begg's and Egger's tests were used to determine publication bias. A p-value of 0.05 or below was deemed statistically significant for all two-sided tests. The present meta-analysis was able to find out the significant protective association between rs743506 and migraine after using dominant (OR: 0.66, CI [0.49-0.86]), over-dominant (OR: 0.56, CI [0.42-0.75]), codominant model (OR: 0.58, CI[0.43-0.77]). Only significant risk association was found between rs1799983, rs3918226, and risk of migraine with aura after utilizing recessive and codominant models i.e., HR vs HW and HR vs HT. The present meta-analysis showed that rs743506 showed a protective association in comparison to rs1799983, rs3918226 which showed significant risk in the MA group. Also, TSA showed non-significant results and therefore, in conclusion, more studies are required to establish risk.

A Comprehensive Investigation into the Association Between Mthfr C677t, A1298c, and Ace I/D Variants and Risk of Migraine: an Updated Meta-Analysis of Genetic Association Studies with Trial Sequential Analysis and Meta-Regression.

Many homeostatic genes are thought to play a role in the susceptibility to migraine, making it a highly complex neurovascular disease. In this meta-analysis, our primary objective was to evaluate whether or not MTHFR variants (such as C677T and A1289C) and ACE I/D were associated with an increased risk of migraine. Using a PRISMA-based systematic literature-review guideline, internet sources such as PubMed and Google Scholar were searched to identify the genes of interest and migraine risk. To pool the data, odds ratios with 95% confidence intervals were calculated utilizing different genetic models. Cochran's Q Test and I2 statistics were used to access heterogeneity, while Begg's and Egger's tests were used to identify publication bias. All tests were two-sided, and a p-value of < 0.05 was regarded as statistically significant. The present meta-analysis observed that the C677T variant is significantly associated with the increased risk of migraine (allele model: OR:1.19, CI [1.07-1.33], I2 = 78%) and its clinical subtype i.e., MA (allele model: OR: 1.26, CI [1.09-1.45], I2 = 80%) in the overall population. Concerning the ACE- I/D, it significantly increased the risk of overall migraine and both clinical subtypes after utilizing the dominant genetic models (OR: 1.14, CI [1.01-1.29], I2% = 32). Concerning the MTHFR A1289C, only the codominant model (HR vs HT) and recessive model significantly increased the risk of overall migraine. Therefore, the findings of the present meta-analysis showed that MTHFR-C677T is an important risk factor for migraine and its clinical subtype.

Enlightening the association between TNF-α -308 G > A and migraine: a meta-analysis with meta-regression and trial sequential analysis.

BACKGROUND: Migraine is a complex neurological disorder that is characterized by a "lower threshold of neuronal hyperexcitability" with distinctive periodicity and complex vascular dysfunction. Genetic factors have impacted incredibly on the susceptibility of migraine and one such example is the TNF-α 308G > A. AIM: Therefore, we aim to provide a glimpse of the association of the TNF-α 308G > A risk on the susceptibility of migraine. METHOD: The pooled odds ratio with the associated 95% of confidence interval were calculated using different genetic models. Heterogeneity was accessed by using Cochran's Q Test and I2 statistics and Begg's and Egger's tests were used for finding the publication bias, tests were two-sided, and a p-value of < 0.05 was considered statistically significant. The Trial Sequential Analysis with Meta-regression Analysis were also utilized to find out the sample size requirement for meta-analysis to avoid type I error and source of heterogeneity respectively. RESULT: A total of 13 studies with cases: 7193 and controls: 23,091 were included and after using different genetic models, no overall association with migraine and its clinical subtype migraine with aura was observed (Allele model "OR: 1.28, 95% C.I. [0.96-1.69] and OR: 0.99,95% C.I. [0.69-1.42]) respectively. Interestingly, after sub-grouping using the "ethnicity criteria" in the migraine group, it was observed that the allelic genetic model and the dominant model were found to be significantly associated with the Asian ethnic group (OR: 1.79, 95% C.I. [1.13-2.84], and OR: 1.85, 95% C.I. [1.0927; 3.1580]. CONCLUSION: In conclusion, the present meta-analysis has provided evidence that 308G > A increases the risk of migraine only in the Asian population.

An Association Study of ESR1-XbaI and PvuII Gene Polymorphism in Migraine Susceptibility in the Jammu Region.

INTRODUCTION: Migraine is a neurovascular disorder and is clinically characterized by episodic attacks of mild to severe headaches. Due to the involvement of multiple environmental and genetic factors, it has become a much more complex neurological condition to understand. Apart from the environmental variables, a plethora of genes have been implicated, and one such example is ESR1. The present study was focused to find out the association of two important polymorphisms, namely, PvuII and XbaI of the ESR1 with migraine in the population of Jammu and Kashmir (UT). METHODS: The PCR-RFLP genotyping method was utilized to detect PvuII and XbaI polymorphism, and the result was confirmed by statistical analysis. RESULTS: Although we did not find a signification association of ESR-PvuII polymorphism with migraine susceptibility {OR: 1.14 at 95% CI [0.76-1.71] (p value 0.5)}, a strong association was found with the clinical subtype of migraine; migraine with aura (MA) {OR: 2.014 at 95% CI [1.069-3.792] (p value 0.028)}. Furthermore, a significant association of ESR-XbaI polymorphism was observed with migraine {OR: 1.908 at 95% CI [1.252-2.907] (p value 0.002) and its both clinical subtypes; migraine without aura (MO) {OR: 1.870 at 95% CI [1.186-2.950] (p value 0.006)} and MA {OR: 2.014 at 95% CI [1.069-3.792] (p value 0.028)}. CONCLUSION: In conclusion, ESR1-XbaI polymorphism is significantly associated with migraine risk including both subtypes (MA and MO) in the North Indian population of Jammu.

Migraine as an inflammatory disorder with microglial activation as a prime candidate.

BACKGROUND: The lower threshold of neuronal hyperexcitability has been correlated with migraines for decades but as technology has progressed, it has now become conceivable to learn more about the migraine disease. Apart from the "cortical spreading depression" and "activation of the trigeminovascular system", inflammation has been increasingly recognized as a possible pathogenic process that may have the possibility to regulate the disease severity. Microglial cells, the prime candidate of the innate immune cells of central nervous tissue, has been associated with numerous diseases; including cancer, neurodegenerative disorders, and inflammatory disorders. AIM: In this review, we have attempted to link the dot of various microglial activation signaling pathways to enlighten the correlation between microglial involvement and the progression of migraine conditions. METHOD: A structured survey of research articles and review of the literature was done in the electronic databases of Google Scholar, PubMed, Springer, and Elsevier until 31 December 2021. RESULT & CONCLUSION: Of 1136 articles found initially and screening of 1047 records, 47 studies were included for the final review. This review concluded that inflammation and microglial overexpression as the prime candidate, plays an important role in the modulation of migraine and are responsible for the progression toward chronification. Therefore, this increases the possibility of preventing migraine development and chronification by blocking microglia overexpression.

The complexities of migraine: A debate among migraine researchers: A review.

Migraine is indeed a neurovascular disorder for which several genes have been identified in this era of Genome-Wide Association Studies (GWAS) and neuroimaging studies have already revealed structural changes and different mechanisms that cause migraine, but the exact cause of this debilitating and disabling neurovascular disorder remained unclear. Low neuronal hyperexcitability ("the migrainous brain") is set and hindered by genetic and environmental factors, respectively. Migraine is also found to be associated with different diseases (co-morbidity). There is still a subject of contention: is migraine a disease of evolution or disease of pathology? This research review seeks to provide a brief overview on the genetics of disorders, structural abnormalities in the brain, CSD-like symptoms, and faulty Trigeminovascular System activation for migraine pain phenotype. This review briefly covered here to provide some ideas that may also be utilized in migraine research and to serve as motivation for future research.

Algorithm for sample availability prediction in a hospital-based epidemiological study spreadsheet-based sample availability calculator.

Looking at the population's behavior by taking samples is quite uncertain due to its big and dynamic structure and unimaginable variability. All quantitative sampling approaches aim to draw a representative sample from the population so that the results of the studying samples can then be generalized back to the population. The probability of detecting a true effect of a study largely depends on the sample size and if taking small samples will give lowers statistical power, higher risk of missing a meaningful underlying difference. The probability of rejecting the null hypothesis i.e., finding significant difference using the sample largely depends upon the statistical power. There are a lot of online tools used for calculating the sample size, but none tell us about the availability of samples from single site in a fixed span. This study aims to provide an efficient calculation method for the availability of samples during a specific period of a research study which is an important question to be answered during the research study design. So, we have designed a spreadsheet-based sample availability calculator tool implemented in MS-Excel 2007.

Black fungus immunosuppressive epidemic with Covid-19 associated mucormycosis (zygomycosis): a clinical and diagnostic perspective from India.

The catastrophic phase of Covid-19 turns the table over with the spread of its disastrous transmission network throughout the world. Covid-19 associated with mucormycosis fungal infection accompanied by opportunistic comorbidities have emerged the myriad of complications and manifestations. We searched the electronic databases of Google Scholar, PubMed, Springer, and Elsevier until June 05, 2021, using keywords. We retrieved the details of confirmed and suspected mucormycosis patients associated with Covid-19. We analyzed the case reports, treatment given for Covid-19, steroids used, associated comorbidities, mucormycosis site involved, and patients survived or dead. Overall, 102 patients of mucormycosis associated with Covid-19 have been reported from India. Mucormycosis was predominant in males (69.6%) rather than females (19.6%), and most of the patients were active Covid-19 cases (70.5%). Steroids were mostly used (68.6%) for the treatment of Covid-19 followed by remdesivir (10.7%). Patients were suffering from diabetes mellitus (88.2%) and severe diabetic ketoacidosis (11.7%). Mucormycosis affects the sino-nasal (72.5%), orbit (24.5%), central nervous system (18.6%), and maxillary necrosis (13.7%) of the patients. The Mortality rate was recorded as 23.5%, and recovery rate was 2.9%. Diabetes mellitus cases are highest in India as compared to other countries, and prevalent use of steroids with the background of Covid-19 becomes an opportunistic environment for mucormycosis fungal infection to survive.

Neuroepidemiology study of headache in the region of Jammu of north Indian population: A cross-sectional study.

Background: Headache disorders now represent a major public health problem globally. It is more prevalent in developing countries with the rising trends of headache disorders observed in young adults affecting their quality of life negatively. Very little information is available on the epidemiology of headache disorders in the Jammu Division of the north Indian population. Aim: The aim of the present study was to find out the prevalence of headache and its two major types, i.e., migraine and tension-type headache (TTH), in the population of the Jammu Division. Methods: The present study was conducted in two phases: (Phase I: face-to-face interview and Phase II: E-based sampling) and the sufferers of headaches were incorporated into the study based on the International Classification of Headache Disorder-3 (ICHD-3) criteria for a representative sample. Frequency distribution and mean ± standard deviation were used in descriptive statistics to describe the data sets, while a t-test, chi-square test, multiple logistic regression, and prevalence ratio were used in inferential statistics. Results: In the present study, a total of 3,148 patients were recruited, with an overall prevalence of headache of 53.84%, with a majority of females (38.18%) over males (15.66%). As regards the type of headache, migraine was found to be of the more prevalent (33.25%) type than the TTH (20.58%). Females suffering from migraine showed the highest prevalence (25.28%), in contrast to females suffering from the TTH (12.89%). Sociodemographic variables, such as gender [female; AOR = 2.46, 95% CI (2.12-2.85), p-value < 0.0001] and marital status [married; AOR: 1.46, 95% CI (1.11-1.92) p-value = 0.006], showed a significant association with the headache. Conclusion: The present study shows that the prevalence of headache is high in the Jammu Division of Jammu and Kashmir (J&K) India, with migraine being the highly prevalent type.