Meta-analysis of Association between Helicobacter pylori Infection and Epilepsy

C l i n M e d International Library Citation: Yao G, Wang P, Xiang-Dan L, Ting-Min Y (2016) Meta-analysis of Association between Helicobacter pylori Infection and Epilepsy. Int J Brain Disord Treat 2:016 Received: September 08, 2016: Accepted: December 02, 2016: Published: December 06, 2016 Copyright: © 2016 Yao G, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Yao et al. Int J Brain Disord Treat 2016, 2:016

Recently, there has been some research interest in the association between H. pylori infection and epilepsy.Several studies evaluating the possible association between H. pylori infection and epilepsy have been published [10][11][12][13][14][15].Some studies have reported a significant

Statistical analysis
Calculation of dichotomous variables was conducted using the odds ratio (OR) with the 95% confidence interval (CI) as the summary estimates to measure the strength of the association of H. pylori infection and Epilepsy.Heterogeneity was tested using the I 2 statistic test, which is a quantitative measure of inconsistency across studies.I 2 values of above 25%, 50% and 75% being considered to indicate low, medium, and high heterogeneity, respectively.Heterogeneity was also determined by Q-test, and it was considered indicative of significant heterogeneity when P values were less than 0.1.When the effects were assumed to be homogeneous (I 2 < 50%) a fixed-effects model was used; otherwise, the random-effects model was more appropriate [16].Statistical significance was set at P values of less than 0.05.The meta-analysis was performed using Review Manager 5.3 software.

Identification of eligible studies
We identified 54 articles from PubMed, EMBASE, Cochrane Library, Web of Science, Google Scholar and CINAHL.Of these articles most were excluded after reading the titles and abstracts, mainly because they were reviews or were not relevant to the metaanalysis, leaving 11 that appeared to fulfill the inclusion criteria.Following more thorough scrutiny, an additional 7 articles were excluded.Finally, a total of 4 prospective articles including 232 cases of Epilepsy and 186 participants were included in the meta-analysis [10][11][12][13].A detailed flowchart of the selection process is presented in figure 1.

Study characteristics
The main characteristics of the 4 included studies are presented in table 1.Four studies involved 232 patients with epilepsy, with a total H. pylori infection rate of 46.98% (109/232).The sample size of the control groups was 186, of which 49 were H. pylori-positive (26.34%).Concerning the H. pylori measure methods, two studies used ELISA, and two studies used the 13 C urea breath test ( 13 C-UBT).Okuda, et al. [11] divided the epilepsy subjects into two subgroups: idiopathic generalized epilepsy (IGE) and idiopathic localizationrelated epilepsy (ILE).Ozturk, et al. [12] separated the Epilepsy patients into poor prognosis and good prognosis groups.Asadi-Pooya, et al. [10] determined the frequency of infection with H. pylori among two groups of patients with epilepsy: patients with idiopathic generalized epilepsy (IGE) and patients with temporal lobe epilepsy (TLE) due to mesial temporal sclerosis.Razak, et al. [13] investigated the association of H. pylori infection with generalised epilepsy and partial epilepsy.
Using stratified analysis based on different methods, the data  large-scale population surveys [21]. 13C-UBT is a detection method based on the carbon dioxide and ammonia produced by H. pylori converting urea and has high specificity and sensitivity [21]. 13C-UBT reveals the active (present) infection, whereas the serology can reveal the past infection.However, it may be impossible to directly compare the 13 C-UBT results due to the difference in UBT protocols across different clinical centers generated differences in breath sample collection times and intervals, as well as influences on delaying gastric emptying [21,22].
There are some limitations in our study.First, the analysis was conducted on a small number of case-control studies, and the cases included in these studies are also limited and lack of high-quality data.Second, the lack of individual data has limited further subgroup analyses of gender and epilepsy sub-type.Finally, some articles published in non-English languages might be missed.
In summary, the present study showed that the association between epilepsy and H. pylori infection is a significant positive correlation.Whether H. pylori infection is a risk factor for epilepsy should thus be addressed in large-scale and prospective studies.revealed that the prevalence of H. pylori infection in epilepsy patients was greater than that in control group by using ELISA in two studies (OR = 5.36, 95% CI: 2.62-10.95,P < 0.00001), but it was not statistically significant difference when using 13 C urea breath test in other two studies (OR = 1.36, 95% CI: 0.75-2.46,P = 0.32) (Figure 3).

Discussion
The association between epilepsy and H. pylori infection is controversial [10][11][12][13][14][15].In this meta-analysis we provide an overview of the relationship between H. pylori positiveity and epilepsy with a total of 418 subjects from four eligible studies.Overall the prevalence of H. pylori infection in epilepsy patients (46.98%, 109/232) was higher than in control individuals (26.34%, 49/186) (P = 0.02), indicating that H. pylori infection may be a risk factor for epilepsy.
Epilepsy may be triggered by immunological mechanisms as a result of H. pylori infections.Autoimmunity was recently suggested to be involved in the pathology of epilepsies [17].Bartolomei, et al. [18] found that detection of anti-GM1 antibodies could allow identification of patients with partial epilepsy associated with an autoimmune response.H. pylori could indirectly influence the brain function due to the release of multiple cytokines such as IL-1,IL-6,TNF-α,which involved in the blood-brain barrier (BBB) disruption and pathogenesis of neuronal inflammatory damage in epilepsy [19,20].Kountouras, et al. [20] have hypothesized that H. pylori might be a potential therapeutic target in epilepsy.
We conducted a further analysis based on different detection methods, the results showed that the prevalence of H. pylori infection in epilepsy patients was higher than that in control groups by using ELISA [11,12], but it was not statistically significant difference using 13 C-UBT [10,13]

Figure 1 :• Page 3 of 4 •
Figure 1: Flow diagram of the study selection process.

Figure 3 :
Figure 3: Subgroup analysis according to different detection methods for the association of H.pylori infection with Epilepsy.
Yao et al.Int J Brain Disord Treat 2016, 2:016 group and the control group.Studies were excluded if: (1) The studies had no control groups; (2) The articles were review articles, laboratory studies, or studies of animals.To ensure homogeneity in data the two investigators performed the data extraction independently.

Table 1 :
Characteristics of the 4 included studies.

ratio Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI Total (95% CI) 232 186 100.0% 2.58 [1.15, 5.82]
. The anti-H.pylori IgG-ELISA is a common method for detecting H. pylori seropositivity in clinics.It is well suitable for

Figure 2 :
Overall meta-analysis of the prevalence of H. pylori infection in the epilepsy group compared with the control group.