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 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 53  |  Issue : 2  |  Page : 84-88

Helicobacter pylori infection in Egyptians with Parkinson's disease: incidence and the effect on motor fluctuation and response to levodopa


1 Department of Neurology, Mansoura University, Cairo, Egypt
2 Department of Internal Medicine, Mansoura University, Cairo, Egypt
3 Department of Neurology, Misr University for Sciences and Technology, Cairo, Egypt

Date of Submission20-Jan-2016
Date of Acceptance02-Mar-2016
Date of Web Publication2-Jun-2016

Correspondence Address:
Mohammed El-Sherif
Department of Neurology, Mansoura Faculty of Medicine, Mansoura University, Mansoura 35516, Dakahlia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-1083.183408

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  Abstract 

Background
Gastrointestinal tract infection with Helicobacter pylori (HP) can inhibit levodopa (LD) in Parkinson's disease (PD) patients, leading to motor fluctuation.
Objectives
The aim of this study was to identify the incidence of HP in PD patients compared with healthy controls and its effect on motor fluctuation, response to treatment, and quality of life.
Patients and methods
Serum IgG Abs against HP urease were detected using enzyme-linked immunosorbent assay. We compared the incidence of HP infection in PD patients and controls. We compared PD patients with positive HP (PD positive) and PD patients with negative HP infection (PD negative) with regard to clinical features, the Unified PD Rating Scale (UPDRS) scores, Hoehn and Yahr (H and Y) stages, PD Questionnaire for the quality of life (PD-Q39), and PD Nonmotor Symptoms Questionnaire (PD NMSQ).
Results
Fifty Egyptians with PD were included. Forty-six percent of patients were HP positive compared with 20% in the control group; the difference was statistically significant (P = 0.043). In PD-positive patients, the total UPDRS and PD-Q39 scores were significantly higher in comparison with PD-negative patients (P < 0.005 and P < 0.001, respectively). The differences were not significant with regard to the total PD NMSQ score and H and Y stages between the two groups of patients. The LD onset period was significantly greater in PD-positive patients by nearly 14 min in comparison with PD-negative patients. There was a significantly prolonged on-duration time in PD-positive patients in comparison with PD-negative patients.
Conclusion
There is a high incidence of HP infection in PD. HP affects the response to LD and can deteriorate motor manifestations and the quality of life.

Keywords: Helicobacter pylori , motor fluctuation, Parkinson′s disease


How to cite this article:
Esmael A, El-Sherif M, Shabana HR, Elazzouny AA. Helicobacter pylori infection in Egyptians with Parkinson's disease: incidence and the effect on motor fluctuation and response to levodopa. Egypt J Neurol Psychiatry Neurosurg 2016;53:84-8

How to cite this URL:
Esmael A, El-Sherif M, Shabana HR, Elazzouny AA. Helicobacter pylori infection in Egyptians with Parkinson's disease: incidence and the effect on motor fluctuation and response to levodopa. Egypt J Neurol Psychiatry Neurosurg [serial online] 2016 [cited 2018 May 27];53:84-8. Available from: http://www.ejnpn.eg.net/text.asp?2016/53/2/84/183408


  Introduction Top


Parkinson's disease (PD) is the second most frequent neurodegenerative disease after Alzheimer's disease, with many heterogeneous manifestations such as motor and nonmotor symptoms [1]. Clinically, it is diagnosed by the existence of two or three motor characteristics: bradykinesia in addition to rigidity or tremor at rest (or both) [2].

Helicobacter pylori (HP) is a gram-negative, microaerophilic bacterium and is a familiar contagion of the gastrointestinal tract and usually coexists with duodenal and gastric ulcers, with an approximate prevalence of 50% worldwide. In Egypt, its prevalence in adults is 90% [3],[4],[5].

Diagnostic tests for HP infection involve endoscopic and nonendoscopic approaches. The two methods used were the direct method, which includes tests for culture and microscopic expression of the organism, and the other was the indirect method, which includes tests for stool antigen, urease usage, or an antibody reaction. The selection of the appropriate test relies on accessibility and cost and comprises a differentiation between tests used to determine a detection of the contagion and those used to check its eradication.

There are other significant determinants such as the clinical status, inhabitant prevalence of infection with HP, the likelihood of contracting the HP contagion, dissimilarities of the test efficiency, and determinants that may affect the findings - for example, the use of antibiotics (not taken 4 weeks before testing) and usage of antisecretory treatment [free from taking proton pump inhibitors or histamine H2-receptor antagonists (H2RAs) for at least 2 weeks]. The enzyme-linked immunosorbent assay serology test for HP infection has a sensitivity of 85-92%, a specificity of 79-83%, and positive predictive value of 64%. It is a good predictor method for the detection of the infection in the developing countries, as it is cheap and readily available [5].

There is an evidence that HP infection affects the pharmacokinetics (especially the absorption) of some drugs in the gastrointestinal tract [6]. One such drug is levodopa (LD), the main drug used to treat PD [7]. After the honeymoon period of LD, it shows marked decrease in the efficacy in some PD patients, which may be due to differences in the rate of absorption [6].

HP may affect the LD pharmacokinetics and bioavailability by interfering with the duodenal mucosa and the reactive oxygen species products that would deactivate the LD [7],[8],[9]. The inconsistent entrance of LD through the blood-brain barrier as the reason of erratic absorption would cause many PD complications, especially motor fluctuation (MF) [10],[11]. Many studies of HP and PD reported that between 37 and 59% of PD patients are HP-positive [6].


  Aim of the work Top


The aim of this study was to determine the incidence of HP in patients with PD compared with controls and its effect on the MF, response to treatment, and subsequently the quality of life.


  Patients and methods Top


The present study included 50 PD patients recruited from the neurology outpatient clinics at the neurology and neurosurgery center in Mansoura University Hospitals (NNC-MUH). All Egyptian PD patients provided informed consent to participate in this study. The UK Parkinson's Disease Society Brain Bank criteria were used to diagnose the studied group with idiopathic PD. In addition, they were taking LD as a monotherapy. The studied group was selected according to the presence of MF, especially the delayed 'on' or the 'wearing-off'. The study protocol was approved by the Local Ethical Committee at the hospital.

Patients with a drug history of antipsychotics, proton pump inhibitors, or H2RAs of at least 2 weeks, patients taking antibiotics 4 weeks before testing, patients taking prokinetics, and those with a history of gastric surgery were excluded from the study. We also excluded patients who showed manifestations of secondary  Parkinsonism More Details (gaze palsy, pyramidal features, and cerebellar ataxia) or Parkinson's plus syndromes on neurological examination.

The control group included 20 age and sex matched participants who neither complained of neurological disease nor were relatives to PD patients.

Baseline data including demographic characteristics, previous antibiotic use, medical and medication history, and a presence of gastrointestinal symptoms were recorded. Patients were classified into two categories based on HP serological analysis: the first one comprised HP-positive patients and the second category comprised HP-negative patients. Thereafter, comparative analysis was carried out between the two groups with regard to PD patient's MF, response to treatment, symptom severity, and quality of life. Moreover, clinical monitoring was carried out to assess the LD kick-in time 'onset' and the extent of the on-period, and home diaries were reviewed that were completed over the course of 72 h before the HP screening test (at 30-min intervals over a 24-h period). We instructed them to indicate their encountered kick-in time 'onset' if it was less than 30 min.

The studied patients were examined using different objective assessments scales. First, we used the Unified PD Rating Scale (UPDRS), which consists of six parts: part I, for the assessment of behavior, mood, and mentation; part II, for the assessment of the activities of daily life; part III, for the motor assessment; part IV, for the complications of the treatment; part V, for the Hoehn and Yahr staging scale; and, part VI, for the Schwab and England scale [12].

Second, we used the modified Hoehn and Yahr stages (H and Y stages) during the treatment. It is a system used to demonstrate how the symptoms of PD progress. It included stages 1 through 5. Recently, a modified scale was published with the inclusion of stages 1.5 and 2.5 to assist in the description of the intermediate course of the disease [13].

Third, the PD Questionnaire for the quality of life (PD-Q39) that had eight sectors ranging from 0 to 100 was used; the higher the score, the worse the quality of life [14]. Finally, PD Nonmotor Symptoms Questionnaire (PD NMSQ) was used, which includes 30 questions to identify the different nonmotor symptoms [15],[16].

The biochemical analysis for the detection of antibodies to HP serum IgG antibodies against HP urease were detected using a commercial enzyme-linked immunosorbent assay kit. The manufacturer's instructions were followed (Pylori-Staty kit; BioWhittaker, Walkersville, Maryland, USA). All samples were checked indiscriminately and database was tested anonymously without any connection to individual recognition [17].

Statistical analysis

All statistical analyses were performed by a statistician using SPSS 20.0 for Windows statistical software package (University of California, Irvine, USA). Numerical data were presented as mean and SD. The independent t-test was used to compare HP-positive and HP-negative patients. Each group variable was compared using the χ2 -test. A P value less than 0.05 was considered statistically significant.


  Results Top


The study included 50 Egyptian PD patients, 27 (54%) male and 23 (46%) female, who had a mean age of 64.2 ± 10.5. The incidence of HP infection was statistically significantly higher in the studied patients in comparison with the healthy control group (46 and 20%, respectively; P = 0.043) [Table 1].
Table 1: Demographic data and HP infection in PD patients and controls

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As regards the total UPDRS, it was statistically significantly higher in HP-positive patients in comparison with the HP-negative patients (P < 0.005). In addition, the PD-Q39 scores were statistically significantly higher in HP-positive patients compared with HP-negative patients (P < 0.001). However, as regards the total PD NMSQ score (P = 0.811) and the Hoehn and Yahr stages (P = 0.635), the differences were not significant between the two groups [Table 2].
Table 2: Relationship between staging, UPDRS scores, and quality of life and HP infection in PD patients

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The LD onset time was significantly longer in the HP-positive group by nearly 14 min compared with the HP-negative group (43.2 ± 21.52 vs. 29.52 ± 15.9; P = 0.011). Similarly, the extent of the on-period 'on-duration' was significantly prolonged in the HP-negative group when compared with the HP-positive group (290.4 ± 142.09 vs. 234.22 ± 77.6; P = 0.041). These results indicate a better response to LD therapy in negative HP patients [Table 3].
Table 3: Effect of HP infection on onset and duration of on-state response to levodopa

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  Discussion Top


PD prevalence was 57 to 230 per 100 000 inhabitants [18]. The prevalence in the Arab world was variable. The highest prevalence was seen in Egypt (Assiut Governorate), followed by Tunisia, Libya (Benghazi), and Kingdom of Saudi Arabia (659/100 000, 216/100 000, 31.4/100 000, and 27/100 000 inhabitants, respectively) [19-22].

HP prevalence fluctuates from region to region, ranging from 61 to 76% in the Far East, 36 to 52% in Western Europe, and 34 to 48% in North America [23]. However, in Korea, the total seropositivity ratio of HP was 56% [24]. HP prevalence increased with age at a rate of 1% per year [3].

The main observation of the present research was that 46% of the Egyptian patients studied were positive for HP infection, and that these patients had higher total UPDRS, PD-Q39, and MF (LD onset time and prolonged on-duration time) compared with PD patients with negative HP infection. This indicates that HP infection may modify LD uptake and may be responsible for MF in PD. These are in agreement with the findings of Pierantozzi et al. [25], who stated that HP prompted intervention with LD clinical reaction due to the altered drug uptake, presumably related to active gastroduodenitis.

We utilized the noninvasive serology method to track HP infection. It has quickly become one of the most useful gold standard methods for the detection of an active HP infection. This evidence was a rationale for using the serology method rather than the invasive tests such as the endoscopic biopsy to display HP infection [17]. HP may influence LD uptake by many processes (breakdown of the drug by chemical mechanisms, and lagged distribution into the duodenum) [25],[26]. The interruption of LD uptake by HP contagion has an unfavorable impact on LD 'onset' time and 'on-time' duration that leads to MF. Erratic LD uptake may cause the pulsatile stimulation of dopamine receptors, leading to MF in PD [27],[28],[29],[30].

Rahne and colleagues studied PD patients, with only 27% being HP infected. The total Hoehn and Yahr scores were three in each HP-infected patients and also the matched cluster. However, HP-infected patients had decreased total UPDRS-IV score of 4.8 ± 3.0 versus 7.7 ± 3.8 (P < 0.05) [31]. Moreover, Hashim et al. [32] studied PD patients, with 32.9% being HP-positive with considerably worse total UPDRS and PD-Q39 scores. These studies are in agreement with our findings, as there is a higher proportion of HP-positive patients (46%), compared with that reported in previous studies (27 and 32.9%), with more affection in PD severity scales.


  Conclusion Top


There is a high prevalence of HP infection in PD patients. Results suggest that HP infection affects the response to LD and deteriorates motor symptoms and quality of life in those patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.[33]

 
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    Tables

  [Table 1], [Table 2], [Table 3]


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