Identifying genetic variants for age of migraine onset in a Han Chinese population in Taiwan

BackgroundConsidering the involvement of genetics in migraine pathogenesis in diverse ethnic populations, genome-wide association studies (GWAS) are being conducted to identify migraine-susceptibility genes. However, limited surveys have focused on the onset age of migraine (AoM) in Asians. Therefore, in this study, we aimed to identify the susceptibility loci of migraine considering the AoM in an Asian population.MethodsWe conducted a GWAS in 715 patients with migraine of Han Chinese ethnicity, residing in Taiwan, to identify the susceptibility genes associated with AoM. Based on our standard demographic questionnaire, the population was grouped into different subsets. Single-nucleotide polymorphism (SNP) associations were examined using PLINK in different AoM onset groups.ResultsWe discovered eight novel susceptibility loci correlated with AoM that reached the GWAS significance level in the Han Chinese population. First, rs146094041 in ESRRG was associated with AoM ≤ 12 years. The other SNPs including rs77630941 in CUX1, rs146778855 in CDH18, rs117608715 in NOL3, rs150592309 in PRAP1, and rs181024055 in NRAP were associated with the later AoM.ConclusionsTo our knowledge, this is the first GWAS to investigate the AoM in an Asian Han Chinese population. Our newly discovered susceptibility genes may have prospective associations with migraine pathogenesis.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01301-y.     

Effective prophylactic therapy for cyclic vomiting syndrome in children using valproate

This trial sought to evaluate our experience using the antimigraine prophylactic drug, use of valproate for the prophylactic management of cyclic vomiting syndrome (CVS) in children. Thirteen children diagnosed with severe CVS were enrolled. Prophylactic therapy consisted of valproate administered at a dose of 10-40 mg/kg/day. Upon enrollment in the study, all patients underwent diagnostic tests to rule out organic causes of their symptoms. Vomiting was severe enough in all patients to cause dehydration requiring hospitalization for intravenous rehydration. Nine of 13 patients did not respond to numerous previous medical therapies like propranolol, amitriptyline, cyproheptadine, phenobarbital, phenytoin, and carbamazepine. Three of 13 patients required combination therapy with valproate and phenobarbital. Of the 13 patients, two showed complete resolution of their symptoms, nine had marked improvement in their symptoms, as evidenced by infrequent attacks of reduced severity, and two failed to respond to valproate therapy. Four patients experienced relapse with a decreased dosage of valproate. Side effects associated with long-term valproate administration were not observed. Valproate appears to be effective for the prophylactic management of severe CVS, with 85% of all patients achieving at least a reduction in the frequency of attacks.     

内皮型一氧化氮合酶基因+894G/T多态性与偏头痛发病的meta分析

目的分析内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)基因+894G/T多态性与偏头痛发病风险之间的相关性。方法本研究检索时间从建库至2016年10月。纳入评估eNOS多态性(+894G/T)与偏头痛发病风险之间相关性的病例对照研究。初筛得到365篇全文,经筛选后最终5篇纳入meta分析。异质性分析采用I~2检验,文献质量评估采用英国牛津循证医学中心文献严格评价项目。结果与GG+GT基因型相比,TT基因型增加有先兆偏头痛(migraine with aura,MA)的发生风险(OR=1.56,95%CI 1.11~2.20;I~2=0%,P=0.01)。在非高加索人群中,GT+TT基因型可增加偏头痛发病风险(OR=1.53,95%CI 1.08~2.16;I~2=0%,P=0.02)。结论本研究提示内皮型一氧化氮合酶基因+894G/T多态性与偏头痛发病风险之间有一定的关系,并且可能因人群遗传背景的不同与偏头痛亚型有一定关联。     

Prevalence and classification of headache in patients with systemic lupus erythematosus

Studies on the prevalence of headache in systemic lupus erythematosus (SLE) have shown that it varies from 32 to 78%. The purpose of our study was to determine the prevalence and characteristics of headache in SLE compared with patients with different types of diffuse connective tissue diseases (DCTD) and its relationship with clinical and laboratory manifestations of SLE. We studied patients with SLE (SLE group) and patients with DCTD (control group). All patients were made to answer questionnaire to assess the presence of headache, characterized by at least five episodes of headache during the last year, which was classified according to the International Headache Society criteria. A total of 207 patients were studied, 115 in SLE group and 92 in the control group. The 1-year prevalence of headache was 75.7% in SLE group and 66% in the control group. When the groups were analyzed, 66.1% met the diagnostic criteria for migraine in the SLE group compared with 52.2% in the control group (p=0.04) and 13.9% for tension-type headache in SLE group compared with 16.3% in the control group. The former was the only variable that reached statistical significance comparing the two groups. Both headache and migraine were associated with Raynaud’s phenomenon in SLE patients (odds ratio of 2.80, 95% confidence interval: 1.11–7.05, p=0.02 and odds ratio of 2.34, 95% confidence interval: 1.04–5.23, p=0.03, respectively). These results suggest that headache is a common manifestation in SLE and in other DCTD and we cannot exclude the possibility that it may be related to the emotional stress induced by such clinical situations.     

Rizatriptan vs. rizatriptan plus trimebutine for the acute treatment of migraine: a double-blind, randomized, cross-over, placebo-controlled study

Gastroparesis frequently happens during migraine attacks, postponing the onset of action of orally administered drugs. Furthermore, triptans seem to work better in the earlier phases of the migraine attacks. Therefore, associating a gastrokinetic drug with a triptan may translate into better efficacy and higher consistency of response. Trimebutine is an opioid derivative with exclusive action on receptors of the Meissner and Auerbach plexus throughout the digestive tube. It has no absorption or central penetration. Herein we contrast the combination of rizatriptan plus trimebutine with rizatriptan alone in the acute treatment of migraine. Forty patients with migraine consecutively seen in our clinic were randomized to treat two consecutive moderate or severe attacks with one tablet of 10 mg rizatriptan plus one capsule of 200 mg trimebutine and two attacks with the same triptan and placebo, in counterbalanced order. We collected information on the severity of the attack, as well as presence of nausea and photophobia at the time of drug intake, and after 1, 2 and 4 h. Recurrence and adverse events were also contrasted. Sixty-four attacks were treated with each drug regimen. At 1 h postdose, 30 (46.8%) of 64 attacks treated with the combination resolved completely, vs. eight (12.5%) of the rizatriptan-treated attacks, a difference of 34% (P < 0.01). At 2 h postdose, 47 (73.4%) attacks treated with the combination vs. 20 (31.2%) of those treated with rizatriptan alone resolved completely, a difference of 42% (95% confidence interval 26, 58, P < 0.001). Regarding nausea and photophobia, the combination was also associated with significantly better response. Recurrence was similar among the two drug regimens, as well as adverse events. The combination rizatriptan and trimebutine is more effective than rizatriptan alone. The combination does not increase adverse events or recurrence of pain.     

Cognitive function is not impaired in people with a long history of migraine: a blinded study

Little is known about the long-term consequences of migraine for cognitive functioning. This study compared older migraine patients with matched controls on four measures of cognitive ability, in a blinded design. Migraine patients and case-matched controls were recruited from the database records of a pre-existing study of ageing. Data were available from four tests of cognitive ability: verbal/arithmetic problem solving, spatial problem solving, processing speed, and vocabulary. There were no significant differences between the mean scores of migraine and control groups on any of the four cognitive tests. In addition, there were no significant differences between migraine and control groups in the effect of age on any of the four tests. A long history of migraine does not compromise scores on the four cognitive tests used in this study. These tests are predictive of memory and executive functioning in cognitive ageing, but it remains possible that lower-level cognitive processes, particularly as assessed by visual tasks, may be vulnerable to migraine.     

A review of evidence-based medicine and meta-analytic reviews in migraine

The following systematic reviews and meta-analyses are presented and the results discussed: the evidence-based American guidelines, five systematic reviews on naratriptan, rizatriptan, eletriptan, sumatriptan and propranolol; a meta-analysis of sumatriptan, a meta-analysis of acute migraine therapy, a meta-analysis of triptans available in Canada and a large meta-analysis of oral triptans. The systematic reviews of several randomized trials of one drug overcome random effects in estimating treatment effect of the reviewed drug. The results from the large meta-analysis of several drugs are compared with head-to-head comparative trials. Results are generally the same in the meta-analysis and in the comparative trials, with some exceptions. Head-to-head comparisons should remain the 'gold standard' and meta-analyses are a useful supplement in cases when comparative trials are relatively small and when no comparative trials exist.     

Improvement in quality of life and activity limitations in migraine patients after prophylaxis. A prospective longitudinal multicentre study

Improved health-related quality of life (HRQOL) and reduced activity limitations are prime objectives of migraine therapy, but no data on the effect of preventive treatments on these outcomes are available. We monitored changes in HRQOL using the Short Form 36 (SF-36) and headache-related activity limitations using the Migraine Disability Assessment Score (MIDAS) in 141 consecutive migraine without aura patients on prophylaxis. A total of 102 patients completed the 3-month study. Mean (SD) number of headache days/month dropped from 8.0 (3.7) to 5.0 (2.3) (P < 0.001). Mean monthly consumption of acute drugs reduced from 7.4 (3.5) to 4.4 (3.1) (P < 0.001). MIDAS total score reduced (improved) significantly. All SF-36 scale scores increased (improved), most significantly. This first study to assess prospectively the impact of prophylaxis on HRQOL and daily activities in a large series indicates that migraine prophylaxis has the potential to reduce the global burden of migraine on individuals and society.     

Right-to-left shunt and migraine: the strength of the relationship

Several studies have shown that the prevalence of a cardial right-to-left shunt (RLS) in patients with migraine with aura is significantly higher than in patients without migraine. To assess the strength of the possible relationship between RLS and migraine, the literature concerning this subject was systematically reviewed. We identified seven relevant studies. Among patients with RLS migraine with aura was 3.5 times more prevalent than among subjects without RLS [Mantel-Haenszel odds ratio (ORMH) 3.5; 95% confidence interval (CI) 2.1, 5.8]. In patients with ischaemic stroke migraine was more than two times more prevalent in patients with RLS than in patients without RLS (ORMH 2.1; 95% CI 1.6, 2.9). Our review shows that there is a clear association between RLS and migraine, especially migraine with aura. The relationship between RLS and migraine is further substantiated by the observations of disappearance and improvement of migraine symptoms after closure of the foramen ovale. However, the mechanism as well as the question about causality of this association has to be further elucidated.     

A study of oxidative stress in migraine with special reference to prophylactic therapy

Objective: The role of oxidative stress markers in migraine and effect of treatment on these has been reported.

Subjects and methods: One hundred and fifty patients having > four attacks of migraine headache/month were included. Headache severity, Migraine Index (MI) and frequency of headache were noted. 120 patients received repetitive transcranial magnetic stimulation (rTMS) therapy and 30 patients received Amitriptyline (AMT). Recovery was defined by 50% improvement in frequency, severity or reduction in MI. Oxidative stress and antioxidant markers have been estimated in patients before and after treatment and correlate the clinical and outcome parameters.

Results: Glutathione (GSH) (P < 0.001), glutathione-S-transferase (GST) (P = 0.049) and total antioxidant activity (TAC) (P < 0.001) level were significantly reduced in migraine patients. GSH (P = 0.02), GST (P = 0.05) and TAC (P < 0.001) were reduced in ictal migraineurs compared to controls. GSH (P < 0.001) and TAC (P = 0.003) levels increased after treatment compared to the base line.

There is an increase in GSH levels in the patients who had improved following rTMS (P = 0.003); placebo (P = 0.001) and AMT (P = 0.013). TAC levels were also increased following rTMS (P = 0.009) and AMT (P = 0.020).

Conclusion: There is evidence of oxidative stress in migraine pathophysiology. Following treatment, oxidative stress declined following both pharmacological and rTMS.