The Egyptian Journal of Neurology, Psychiatry and Neurosurgery

ORIGINAL ARTICLE
Year
: 2016  |  Volume : 53  |  Issue : 3  |  Page : 151--155

Helicobacter pylori infection in women with nonmenstrual migraine without aura: A case-control study


Hassan M Elnady1, Al-Amir B Mohamed1, Ashraf Khodearya2, Mahmoud Saif-Al Islam3,  
1 Department of Neurology, Faculty of Medicine, Sohag University, Sohag, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Sohag University, Sohag, Egypt
3 Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Sohag University, Sohag, Egypt

Correspondence Address:
Hassan M Elnady
Department of Neurology, Faculty of Medicine, Sohag University
Egypt

Abstract

Background In the last two decades the relation between chronic Helicobacter pylori (HP) infection and migraine has been studied, but the results of these studies are controversial. Objective The aim of this study was to determine whether current or previous exposure to HP infection is a risk factor in women with nonmenstrual migraine (NMM) without aura, a concise subgroup in which environmental factors are dominant. Patients and methods A total of 24 women, with ages ranging from 19 to 60 years, affected by NMM without aura were evaluated in comparison with 24 control women, with ages ranging from 20 to 59 years, without any history of primary headache. In both cases and controls HP infection was evaluated by detection of HP antibodies in serum and HP antigen in stool. Results The prevalence of HP infection was nonsignificantly higher in the migraineurs without aura compared with controls (P = 0.24 and 0.33). Regarding the intensity, duration, and frequency of attacks of migraine no differences were detected between the two groups. Conclusion Our findings do not support HP infection to be a risk factor for NMM without aura.



How to cite this article:
Elnady HM, Mohamed AAB, Khodearya A, Saif-Al Islam M. Helicobacter pylori infection in women with nonmenstrual migraine without aura: A case-control study.Egypt J Neurol Psychiatry Neurosurg 2016;53:151-155


How to cite this URL:
Elnady HM, Mohamed AAB, Khodearya A, Saif-Al Islam M. Helicobacter pylori infection in women with nonmenstrual migraine without aura: A case-control study. Egypt J Neurol Psychiatry Neurosurg [serial online] 2016 [cited 2021 Apr 22 ];53:151-155
Available from: http://www.ejnpn.eg.net/text.asp?2016/53/3/151/193064


Full Text

 Introduction



Migraine is an erratic disorder, the attacks of which vary markedly among individuals, whose specific symptoms may occur in a single attack but not in another, and whose characteristics are rarely steady over a lifetime [1]. Countless factors such as genetics, medications, food, sleep disorders, stress, environmental factors such as noise, light, smells, and humidity, work-related factors, menstruation, head trauma, alcohol, etc. have been documented as risk factors of migraine [2]. In contrast to migraine with aura, migraine without aura appears to be caused by a combination of genetic and environmental factors [3].

Migraine prevalence does not differ between sexes before adolescence. However, there is a significant increase in migraine prevalence in women after menarche, compared with men, and this point inevitably leads to the hypothesis that female sex hormones play a crucial role in migraine pathophysiology [4]. The International Classification of Headache Disorders Third Edition beta version (ICHD-3 beta) describes three different types of migraine without aura: pure menstrual migraine, menstrually related migraine, and nonmenstrual migraine (NMM). These definitions remain in the appendix and are not considered among the core classifications because of doubt by the International Headache Society as to whether they should be regarded as separate entities [5].

Helicobacter pylori (HP) is a gram-negative organism that was identified in 1983. It is one of the most common infections that affect humans [6]. The prevalence of HP infection varies between countries; generally, the prevalence is about 30% in developed countries and up to 80% in developing countries [7]. In some countries in the Middle East, the prevalence of HP infection has been studied using PCR and histopathology. The prevalence of HP infection in Jordan and Bahrain was 77.5 and 79%, respectively. In Egypt, HP infection was found in 86% of biopsy samples [8]. The majority of infected patients with HP have no symptoms and will never develop problems [9]. However, HP is capable of causing several digestive problems, including ulcers, and much less commonly stomach cancer [10],[11],[12]. Besides gastric problems, it has been associated with a number of chronic diseases such as type 2 diabetes, respiratory problems, renal failure, ischemic heart disease, ischemic cerebrovascular disease, Reynaud’s phenomenon, and skin diseases [9].

In the last few years, researchers have focused on the relationship between migraine and HP infection. Some studies have reported a strong positive correlation, and eradication of the bacterium has resulted in a decrease in migraine attacks. In the meantime, others have indicated entirely negative results [13].

The aim of this study was to determine whether current or previous exposure to HP infection is a risk factor in women with NMM without aura, a concise subgroup in which environmental factors are dominant.

 Patients and methods



This is a casecontrol study analyzing 24 women with NMM without aura with ages ranging from 19 to 60 years, who were selected from a series of consecutive patients attending the Neurology Outpatient Clinic of Sohag University Hospital from November 2013 to March 2014. All patients were examined and a detailed questionnaire was completed for each patient. The questionnaire included demographic data, details of headache episodes, duration of migraine, number of attacks, duration of each attack, frequency of attack, relation to menses, location, severity (mild: able to continue with daily activities; moderate: some limitations in daily activities; severe: unable to function), associated symptoms, aura, causative and relieving factors, previous prophylaxes, treatment details, and family history. The diagnostic criteria for NMM without aura used in the current study were according to the third edition of the International Classification of Headache Disorders (ICHD-3 beta) [5]. According to ICHD-3 beta, pure menstrual migraine attacks occur exclusively from days –2 to +3 of menstruation in at least two out of three menstrual cycles and at no other times of the cycle; menstrually related migraine attacks occur on days –2 to +3 of menstruation in at least two out of three menstrual cycles and additionally at other times of the cycle; NMM attacks have no menstrual relationship [5]. Only patients with NMM without aura were included in this study. None of our patients were smokers or alcoholics. Twenty-four healthy women without any history of migraine, with ages ranging from 20 to 59 years, were selected as the control group. Controls were persons accompanying patients in our Inpatient Department. The mean age did not differ between migraineurs and controls. Consent was obtained from participants. The study was approved by the Local Ethical Committee.

Blood and stool samples were taken from all patients and healthy controls. The blood samples were 4-mm samples without anticoagulant for HP antibody detection. HP antibody was detected by means of enzyme-linked immunosorbent assay (ELISA). The reagents required for the sequential ELISA assay include immobilized antigen, circulating antibody, and enzyme-linked species-specific antibody. In this procedure, the immobilization takes place during the assay at the surface of the microplate well through the interaction of streptavidin coated on the well and the exogenously added biotinylated HP antigen. Total serum immunoglobulin E (LgE) was assayed with a programmable Thermo ELISA reader (Finland) (ThermoFisherScientic Co. Walthan, USA) using immunoglobulin IgE Human ELISA kit (Abcam) (Biomatik Co., Wilmington, USA) according to the manufacturer’s guidelines.

HP antigen in stool was detected by following the immunochromatic method, in which the HP antigen reacts with the conjugate-red latex particles sensibilized with anti-HP monoclonal antibody coated to the membrane of the test. The formed HP-conjugate complex, which migrates up the membrane due to capillarity, binds to the specific antibody molecules fixed to the reaction zone. The excess of complex keeps migrating through the membrane until it reaches the C zone of control, where it will bind to another specific antibody coated to the membrane, forming a green band. The presence of the green band confirms the functionality of the test.

Statistical analysis

Data were grouped, tabulated, and statistically analyzed using the Statistical Package for the Social Sciences (SPSS version 20, SPSS Inc., Chicago, Illinois, USA).

The χ2-test was used for categorical comparisons of data. Differences in the mean values of continuous measurements were tested by means of the Student t-test. A P-value of less than 0.05 was considered significant.

 Results



Clinical characteristics of the study population diagnosed as NMM without aura have been summarized in [Table 1].{Table 1}

Previous exposure to HP infection (serum positiveness) was detected in 13 (54.1%) out of the 24 migraineurs and in eight out of 24 (33.3%) controls. The prevalence of previous exposure to HP infection was nonsignificantly higher in the migraineurs (P = 0.24 and odds ratio = 0.42) ([Figure 1]). In contrast, current HP infection (stool positiveness) was found in 10 (41.6%) out of the 24 migraineurs and in five (20.8%) of the controls, with no significant difference between the two groups (P = 0.21 and odds ratio = 0.36) [Figure 2].{Figure 1}{Figure 2}

Among migraineurs, no relationship was found between HP infection (current or previous) and the intensity, duration, or frequency of migraine attacks [Table 2] and [Table 3].{Table 2}{Table 3}

 Discussion



The fact that headache is frequently associated with gastrointestinal disorders [14],[15] and the confirmed association between chronic headache, migraine, and irritable bowel syndrome by several clinical observational and epidemiological studies [16],[17] were the motivating factors for studying the association between migraine and HP infection. There are contradictory results from studies that have examined the relationship between HP infection and migraine [18]. To the best of our knowledge, the present study is the first in Egypt to study the relation between HP infection and NMM without aura. This study showed that HP infection is not a risk factor for NMM without aura. There are several reasons for selecting such a category of patients. First, migraine is more common in women [13]. Second, the effects of hormonal and genetic factors would be neutral when all participants are women and when all cases are suffering from migraine without aura. Third, NMM without aura is one of the entities in the appendix of the ICHD-3 beta. The aim of the appendix is to offer research criteria for a number of novel entities that have not been sufficiently validated by research so far [5].

Our results are in agreement with many earlier reports. Pinessi et al. [19] in a study conducted on migrainous patients found that chronic HP infection is as frequent in patients with migraine as in controls and that HP infection is not associated with any significant difference in the clinical features of the migraine attack. Savi [20] investigated the effects of eradication of HP infection in patients with migraine and found no significant difference in the frequency, duration, intensity, and associated symptoms of migraine attacks. Caselli et al. [21] studied the HP infection prevalence in 36 children suffering from migraine without aura. They found no relation between HP infection and migraine in children. Ciancarelli et al. [22] concluded that, in the absence of any specific link between HP infection and migraine, the association, when present, must be considered as being merely casual. Mavromichalis et al. [23] studied a group of 31 patients suffering from migraine (21 with and 10 without aura) who met the diagnostic criteria of the International Headache Society and who had undergone endoscopic gastric biopsy. They did not find an association between HP antral gastritis and migraine.

Studies with positive results on the association between HP and migraine are not in harmony with each other. One study reported that infection by the highly virulent CagA-positive strains of HP is significantly higher in patients with migraine with aura [24], whereas another study reported that the prevalence of HP infection was significantly greater in migraineurs without aura compared with controls [25]. Also, Gasbarrini et al. [24] attributed the cause of migraine attacks from HP infection to the production of cytokines, especially interleukin-8, which has proinflammatory and vasospastic properties. However, other authors [26] reported that interleukin-10 stimulated by HP could play a vital role in the severity of migraine symptoms in patients with HP infection. Indirectly, Hong et al. [27] found a positive relation between migraine and HP infection by studying the effect of eradication of infection on patients with migraine and reported that the intensity, duration, and frequency of attacks of migraine were significantly lower in all patients in whom HP has been eradicated. However, a finding like that was criticized by other authors [28], who reported that the statement that HP eradication significantly reduced migraine attacks does not essentially indicate a causal role of HP infection in migraines, because antibiotic treatments have widespread and various target effects. In agreement with previous studies [20],[24] the present study has found no relation between the intensity, duration, and frequency of attacks of migraine in patients with HP infection.

The relation between the gastrointestinal tract and brain is a complex one. The brain and the gastrointestinal tract are powerfully linked through neural, endocrine, and immune pathways [29],[30],[31]. The communication occurs in two directions, not only from the brain to the gut but also the other way around. The gut microbiota is an environmental factor that may play an important role. The number of bacteria in the human gut outnumbers human cells by ~10 : 1 [32]. The latest finding on the role of the gut microbiota in the gutbrain axis suggests that the gut microbiota can be associated with brain functions and neurological disorders like migraine [33]. These factors should be addressed and justified when presenting a positive link between HP infection and migraine.

In conclusion, we did not detect an association between HP infection and NMM without aura, but our findings are limited by the small sample size.

Limitation

The principal limitation of the present study is the small sample size. However, we believe that it can be useful to researchers as a trigger for larger studies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Davidoff RAMigraine: manifestations, pathogenesis, and management20022nd edOxfordOxford University Press
2Hosseinzadeh M, Khosravi A, Saki K, Ranjbar REvaluation of Helicobacter pylori infection in patients with common migraine headacheArch Med Sci20117844849
3Russell MBGenetics in primary headachesJ Headache Pain20078190195
4Karlı N, Baykan B, Ertaş M, Zarifoğlu M, Siva A, Saip S et al.Turkish Headache Prevalence Study Group Impact of sex hormonal changes on tension-type headache and migraine: a cross-sectional population-based survey in 2,600 womenJ Headache Pain201213557565
5Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version)Cephalalgia201333629808
6Marshall BJ, Warren JRUnidentified curved bacilli in the stomach of patients with gastritis and peptic ulcerationLancet1984113111315
7Atherton JCThe pathogenesis of Helicobacter pylori-induced gastro-duodenal diseasesAnnu Rev Pathol200616396
8Hussein NRHelicobacter pylori and gastric cancer in the Middle East: a new enigma?World J Gastroenterol20101632263234
9Faraji F, Zarinfar N, Zanjani AT, Morteza AThe effect of Helicobacter pylori eradication on migraine: a randomized, double blind, controlled trialPain Physician201215495498
10Alakkari A, Zullo A, O’Connor HJHelicobacter pylori and nonmalignant diseasesHelicobacter201116Suppl 13337
11De Falco G, Rogena EA, Leoncini LInfectious agents and lymphomaSemin Diagn Pathol201128178187
12Tan VP, Wong BCHelicobacter pylori and gastritis: untangling a complex relationship 27 years onJ Gastroenterol Hepatol201126Suppl 14245
13Su J, Zhou XY, Zhang GXAssociation between Helicobacter pylori infection and migraine: a meta-analysisWorld J Gastroenterol2014201496514972
14Galli F, D’Antuono G, Tarantino S, Viviano F, Borrelli O, Chirumbolo A et al.Headache and recurrent abdominal pain: a controlled study by the means of the Child Behaviour Checklist (CBCL)Cephalalgia200727211219
15Pucci E, Di Stefano M, Miceli E, Corazza GR, Sandrini G, Nappi GPatients with headache and functional dyspepsia present meal-induced hypersensitivity of the stomachJ Headache Pain20056223226
16Jones R, Lydeard SIrritable bowel syndrome in the general populationBMJ19923048790
17Whorwell PJ, McCallum M, Creed FH, Roberts CTNon-colonic features of irritable bowel syndromeGut1986273740
18Tunca A, Türkay C, Tekin O, Kargili A, Erbayrak MIs Helicobacter pylori infection a risk factor for migraine? A case–control studyActa Neurol Belg2004104161164
19Pinessi L, Savi L, Pellicano R, Rainero I, Valfrè W, Gentile S et al.Chronic Helicobacter pylori infection and migraine: a case–control studyHeadache200040836839
20Savi LPHelicobacter eradication and migraineCephalalgia200020346347
21Caselli M, Chiamenti CM, Soriani S, Fanaro SMigraine in children and Helicobacter pyloriAm J Gastroenterol19999411161118
22Ciancarelli I, Di Massimo C, Tozzi-Ciancarelli MG, De Matteis G, Marini C, Carolei AHelicobacter pylori infection and migraineCephalalgia200222222225
23Mavromichalis I, Zaramboukas T, Giala MMMigraine of gastrointestinal originEur J Pediatr1995154406410
24Gasbarrini A, Gabrielli M, Fiore G, Candelli M, Bartolozzi F, De Luca A et al.Association between Helicobacter pylori cytotoxic type I CagA-positive strains and migraine with auraCephalalgia200020561565
25Yiannopoulou KG, Efthymiou A, Karydakis K, Arhimandritis A, Bovaretos N, Tzivras MHelicobacter pylori infection as an environmental risk factor for migraine without auraJ Headache Pain20078329333
26Kang JW, Shin YIThe role of interleukin 10 in the associations between migraine and Helicobacter pylori infectionPain Physician201316E450
27Hong L, Zhao Y, Han Y, Guo W, Wang J, Li X et al.Reversal of migraine symptoms by Helicobacter pylori eradication therapy in patients with hepatitis-B-related liver cirrhosisHelicobacter200712306308
28Mavromichalis IThe role of Helicobacter pylori infection in migraineCephalalgia200323240241
29Collins SM, Surette M, Bercik PThe interplay between the intestinal microbiota and the brainNat Rev Microbiol201210735742
30Cryan JF, Dinan TGMind-altering microorganisms: the impact of the gut microbiota on brain and behaviourNat Rev Neurosci201213701712
31Chen X, D’Souza R, Hong STThe role of gut microbiota in the gut-brain axis: current challenges and perspectivesProtein Cell20134403414
32Belkaid Y, Naik SCompartmentalized and systemic control of tissue immunity by commensalsNat Immunol201314646653
33Van Hemert S, Breedveld AC, Rovers JM, Vermeiden JP, Witteman BJ, Smits MG, de Roos NMMigraine associated with gastrointestinal disorders: review of the literature and clinical implicationsFront Neurol20145241