Role of Chronic Infection and Inflammation in the Gastrointestinal Tract in the Etiology and Pathogenesis of Idiopathic Parkinsonism

Dobbs, R. J.; Dobbs, S. M.; Weller, C.; Bjarnason, Ingua T.; Oxlade, Norman L.; Charlett, André; Al-Janabi, M. A. A.; Kerwin, Robert; Mahler, Robert; Price, Ashley B.

doi:10.1111/j.1523-5378.2005.00331.x

Cited by 54 publications

(67 citation statements)

References 33 publications

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“…This study found H. pylori -IgG positivity in 50% of PD patients, which is consistent with other studies finding prevalence rates of 40–60% among PD patients 1513141516. The prevalence in our population is also similar to that in the general Indian population 17.…”

Section: Discussionsupporting

confidence: 92%

Association ofHelicobacter pyloriwith Parkinson's Disease

et al. 2017

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Background and PurposeParkinson's disease (PD) is a major neurological disorder that requires lifelong treatment, and the combined presence of Helicobacter pylori (H. pylori) infection can increase the required anti-PD medications. We aim to investigate the effect of H. pylori infection in Indian PD patients.MethodsWe prospectively recruited 36 PD patients from December 2007 to January 2011. All patients underwent a detailed neurological evaluation and serological examination for H. pylori infection. Seropositive and seronegative patients were considered to be the cases and controls, respectively. All patients who were seropositive received triple therapy for 2 weeks. Outcome measures of the mean ‘off’ Unified Parkinson's Disease Rating Scale (UPDRS)-III score, mean ‘on’ UPDRS-III score, mean onset time, mean ‘on’ duration, and mean daily ‘on’ time were measured at baseline and at a 3-week follow-up.ResultsH. pylori-IgG positivity was present in 18 (50%) PD patients. The prevalence of men (72.2% vs. 33.3%), mean duration of disease (13.8 vs. 12.5) and mean levodopa equivalent daily dose (824 mg vs. 707 mg) were significantly higher among H. pylori positive patients than in controls (p<0.0001). Controls had a significantly longer ‘on’ duration and daily ‘on’ time, and better ‘on’ UPDRS-III scores. Seropositive patients took a significantly longer time to turn ‘on’ after a levodopa challenge. At the 3-week follow-up, H. pylori eradication significantly improved the mean ‘on’ UPDRS-III score, onset time, ‘on’ duration, and daily ‘on’ time.ConclusionsH. pylori infection was present in 50% of Indian PD patients. H. pylori seropositivity was associated with a poor response to levodopa and increased medication usage, while eradication therapy was associated with better patient outcomes.

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Section: Discussionsupporting

confidence: 92%

Association ofHelicobacter pyloriwith Parkinson's Disease

et al. 2017

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“…This study may also shed light into previous observations; it described the existence of an increased prevalence of peptic ulcer prodromal to idiopathic Parkinsonism [172, 180]. This has prompted some authors to suggest a prominent role of inflammation in gastrointestinal tract in the etiology and pathogenesis of idiopathic Parkinsonism, including a possible role for Helicobacter pylori infections [173, 181]. This infective process is the most prevalent in the world, affecting approximately 50% of the population [182], and it is considered the causative agent of many gastrointestinal and extradigestive conditions.…”

Section: Peripheral Inflammation Enhanced the Inflammation Producesupporting

confidence: 57%

“…It is known that the chance of developing AD is increased twice in aged persons exposed to systemic infections [171]. Furthermore, Strang [172] described the increased prevalence of peptic ulcer prodromal to idiopathic Parkinsonism [173]. Thus, we were interested in using our animal model of PD to study the implication of peripheral inflammation [174].…”

Section: Peripheral Inflammation Enhanced the Inflammation Producementioning

confidence: 99%

Inflammatory Animal Model for Parkinson's Disease: The Intranigral Injection of LPS Induced the Inflammatory Process along with the Selective Degeneration of Nigrostriatal Dopaminergic Neurons

et al. 2011

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We have developed an animal model of degeneration of the nigrostriatal dopaminergic neurons, the neuronal system involved in Parkinson's disease (PD). The implication of neuroinflammation on this disease was originally established in 1988, when the presence of activated microglia in the substantia nigra (SN) of parkinsonians was reported by McGeer et al. Neuroinflammation could be involved in the progression of the disease or even has more direct implications. We injected 2 μg of the potent proinflammatory compound lipopolysaccharide (LPS) in different areas of the CNS, finding that SN displayed the highest inflammatory response and that dopaminergic (body) neurons showed a special and specific sensitivity to this process with the induction of selective dopaminergic degeneration. Neurodegeneration is induced by inflammation since it is prevented by anti-inflammatory compounds. The special sensitivity of dopaminergic neurons seems to be related to the endogenous dopaminergic content, since it is overcome by dopamine depletion. Compounds that activate microglia or induce inflammation have similar effects to LPS. This model suggest that inflammation is an important component of the degeneration of the nigrostriatal dopaminergic system, probably also in PD. Anti-inflammatory treatments could be useful to prevent or slow down the rate of dopaminergic degeneration in this disease.

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“…Case studies [4] and a placebo-controlled efficacy study [5] of H. pylori eradication provided proof of principle for the role of infection in the pathogenesis. In late IP, U-turns in both parkinsonism and cachexia were documented following Helicobacter eradication.…”

Section: Interventional Studiesmentioning

confidence: 99%

Towards Defining a Rigidity-Associated Pathogenic Pathway in Idiopathic Parkinsonism

Dobbs¹,

Charlett

Dobbs³

et al. 2011

Neurodegener Dis

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Helicobacter pylori eradication has a differential effect on the facets of idiopathic parkinsonism (IP): brady/hypokinesia improves, but rigidity worsens. Small intestinal bacterial overgrowth is common in IP and has been described as a sequel to Helicobacter eradication. The hyperhomocysteinaemia of IP is, in part, explained by serum vitamin B₁₂, but the concentration is not explained by Helicobacter status. Moreover, Helicobacter-associated gastric atrophy is uncommon in IP. However, overgrowth both increases B₁₂ utilization and provides a source of inflammation to drive homocysteine production. It is not a bystander event in IP: clouds of lysosomes are seen in duodenal enterocytes. Its candidature for causality of a rigidity-associated pathway is circumstantial: there are biological gradients of rigidity on natural killer and T-helper blood counts, both being higher with hydrogen breath test positivity for overgrowth.

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Role of Chronic Infection and Inflammation in the Gastrointestinal Tract in the Etiology and Pathogenesis of Idiopathic Parkinsonism

Abstract: Categorization, according to presence or absence of Helicobacter infection, was a useful therapeutic tool in late idiopathic parkinsonism.

Cited by 54 publications

References 33 publications

Association ofHelicobacter pyloriwith Parkinson's Disease

Association ofHelicobacter pyloriwith Parkinson's Disease

Inflammatory Animal Model for Parkinson's Disease: The Intranigral Injection of LPS Induced the Inflammatory Process along with the Selective Degeneration of Nigrostriatal Dopaminergic Neurons

Towards Defining a Rigidity-Associated Pathogenic Pathway in Idiopathic Parkinsonism

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