Non-, a Treatable Provocateur of Parkinson's Disease: Hypothesis, Evidence and Species Specificity.

Epidemiological and eradication trial evidence indicates that , a major causative factor in peptic ulcer and gastric cancer, is a driver of the hypokinesia of Parkinson's disease (PD). Psychological (cognitive impairment, depression and anxiety) and gastrointestinal (peptic ulceration and constipation) PD features can precede the symptomatic onset of motor features by decades. We hypothesise that the non- (NHPH), which have farm, companion and wild animals as their main hosts, can have a role in PD aetiopathogenesis.

Bradyphrenia and Tachyphrenia in Idiopathic Parkinsonism Appear, in Part, Iatrogenic: An Observational Study with Systematic Review Background.

We question whether bradyphrenia, slowing of cognitive processing not explained by depression or a global cognitive assessment, is a nosological entity in idiopathic parkinsonism (IP). The time taken to break contact of an index finger with a touch-sensitive plate was measured, with and without a warning in the alerting signal as to which side the imperative would indicate, in 77 people diagnosed with IP and in 124 people without an IP diagnosis. The ability to utilise a warning, measured by the difference between log-transformed reaction times (unwarned minus warned), was termed 'cognitive efficiency'.

Faecal metabolite deficit, gut inflammation and diet in Parkinson's disease: Integrative analysis indicates inflammatory response syndrome.

Background: Gut-brain axis is widely implicated in the pathophysiology of Parkinson's disease (PD). We take an integrated approach to considering the gut as a target for disease-modifying intervention, using continuous measurements of disease facets irrespective of diagnostic divide.

Methods: We characterised 77 participants with diagnosed-PD, 113 without, by dietary/exogenous substance intake, faecal metabolome, intestinal inflammation, serum cytokines/chemokines, clinical phenotype including colonic transit time.

Role of in Neuropsychiatric Disease: A Systematic Review in Idiopathic Parkinsonism.

Interest in an aetiopathogenic role for in neuropsychiatric diseases started with idiopathic parkinsonism (IP), where the cardinal signs can be assessed objectively. This systematic review, using an EMBASE database search, addresses Oxford Centre for Evidence-Based Medicine based questions on the inter-relationship of and IP, the benefits of eradicating in IP and the outcome of not treating. The search strategy was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines: 21 of 204 articles met the inclusion criteria.

Distinctive Pathophysiology Underlying Constipation in Parkinson's Disease: Implications for Cognitive Inefficiency.

Depression is associated with constipation within and outside Parkinson's disease (PD). Since inefficient cognitive-processing (bradyphrenia) features in PD and an enterokinetic agent improved cognitive performance in healthy individuals, bradyphrenia may be associated with constipation. We aim to define the archetypical bowel function of PD, and its association with cognition, mood, and motor features within and outside PD.

Is Associated With Mortality in Parkinson's Disease.

has been implicated in the pathogenesis of Parkinson's disease (PD). Its eradication, in a randomized placebo-controlled trial, improved PD hypokinesia. species zoonosis might explain excess mortality from PD and non-Hodgkin lymphoma in livestock, but not arable, farmers.

Quantifying rigidity of Parkinson's disease in relation to laxative treatment: a service evaluation.

Aim: To estimate whether laxatives prescribed for constipation in Parkinson's disease (PD) could moderate rigidity. Constipation predates diagnosis of PD by decades. Deposition of misfolded protein may begin in the gut, driven by dysbiosis.

Peripheral aetiopathogenic drivers and mediators of Parkinson's disease and co-morbidities: role of gastrointestinal microbiota.

We seek an aetiopathogenic model for the spectrum of Parkinson's disease (PD), functional bowel disease, depression and cognitive impairment. The adopted concept is that systemic immuno-inflammatory processes mediate neuro-inflammation. The model would be based on phenotype, exposome (including gastrointestinal microbiome), milieu (immuno-inflammatory and metabolome), human genetics and their interactions.

Antimicrobial surveillance in idiopathic parkinsonism: indication-specific improvement in hypokinesia following Helicobacter pylori eradication and non-specific effect of antimicrobials for other indications in worsening rigidity.

Background: Following Helicobacter pylori eradication in a placebo-controlled trial, the hypokinesia of idiopathic parkinsonism improved but flexor rigidity worsened.

Methods: We surveyed the effect of all antimicrobial prescriptions in 66 patients with idiopathic parkinsonism over a median of 1.9 (interquartile range 0.

Leukocyte-subset counts in idiopathic parkinsonism provide clues to a pathogenic pathway involving small intestinal bacterial overgrowth. A surveillance study.

Background: Following Helicobacter pylori eradication in idiopathic parkinsonism (IP), hypokinesia improved but flexor-rigidity increased. Small intestinal bacterial-overgrowth (SIBO) is a candidate driver of the rigidity: hydrogen-breath-test-positivity is common in IP and case histories suggest that Helicobacter keeps SIBO at bay.

Methods: In a surveillance study, we explore relationships of IP-facets to peripheral immune/inflammatory-activation, in light of presence/absence of Helicobacter infection (urea-breath- and/or stool-antigen-test: positivity confirmed by gastric-biopsy) and hydrogen-breath-test status for SIBO (positivity: >20 ppm increment, 2 consecutive 15-min readings, within 2h of 25G lactulose).

Towards defining a rigidity-associated pathogenic pathway in idiopathic parkinsonism.

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 B(12), but the concentration is not explained by Helicobacter status.

Differential effect of Helicobacter pylori eradication on time-trends in brady/hypokinesia and rigidity in idiopathic parkinsonism.

Background: We examine the effect of eradicating Helicobacter in idiopathic parkinsonism (IP). Marked deterioration, where eradication-therapy failed, prompted an interim report in the first 20 probands to reach de-blinding. The null-hypothesis, "eradication has no effect on principal outcome, mean stride length at free-walking speed," was rejected.

Blood profile holds clues to role of infection in a premonitory state for idiopathic parkinsonism and of gastrointestinal infection in established disease.

The two-stage neuroinflammatory process, containment and progression, proposed to underlie neurodegeneration may predicate on systemic inflammation arising from the gastrointestinal tract. Helicobacter infection has been described as one switch in the pathogenic-circuitry of idiopathic parkinsonism (IP): eradication modifies disease progression and marked deterioration accompanies eradication-failure. Moreover, serum Helicobacter-antibody-profile predicts presence, severity and progression of IP.

Helicobacter hypothesis for idiopathic parkinsonism: before and beyond.

We challenge the concept of idiopathic parkinsonism (IP) as inevitably progressive neurodegeneration, proposing a natural history of sequential microbial insults with predisposing host response. Proof-of-principle that infection can contribute to IP was provided by case studies and a placebo-controlled efficacy study of Helicobacter eradication. "Malignant" IP appears converted to "benign", but marked deterioration accompanies failure.

Role of chronic infection and inflammation in the gastrointestinal tract in the etiology and pathogenesis of idiopathic parkinsonism. Part 3: predicted probability and gradients of severity of idiopathic parkinsonism based on H. pylori antibody profile.

Background: Eradicating Helicobacter may convert rapidly progressive idiopathic parkinsonism to quieter disease, however only a minority of probands have evidence of current infection.

Aim: To explore the cross-sectional fit of parkinsonism as an extra-alimentary consequence of Helicobacter pylori, using the serum antibody profile.

Methods: A discriminant index for parkinsonism was based on the Western Blot pattern of IgG antibodies against electrophoretically separated H.

Role of chronic infection and inflammation in the gastrointestinal tract in the etiology and pathogenesis of idiopathic parkinsonism. Part 2: response of facets of clinical idiopathic parkinsonism to Helicobacter pylori eradication. A randomized, double-blind, placebo-controlled efficacy study.

Background: Links between etiology/pathogenesis of neuropsychiatric disease and infection are increasingly recognized.

Aim: Proof-of-principle that infection contributes to idiopathic parkinsonism.

Methods: Randomized, double-blind, placebo-controlled efficacy study of proven Helicobacter pylori eradication on the time course of facets of parkinsonism.

Role of chronic infection and inflammation in the gastrointestinal tract in the etiology and pathogenesis of idiopathic parkinsonism. Part 1: eradication of Helicobacter in the cachexia of idiopathic parkinsonism.

Background: Neuronal damage in idiopathic parkinsonism may be in response to ubiquitous occult infection. Since peptic ulceration is prodromal, Helicobacter is a prime candidate.

Aim: To consider the candidature of Helicobacter in parkinsonism with cachexia.

Role of inflammation in gastrointestinal tract in aetiology and pathogenesis of idiopathic parkinsonism.

Idiopathic parkinsonism (IP) is a common disorder, conventionally regarded as neurodegenerative. Its cardinal features, poverty and slowness of movement, muscle rigidity, postural abnormality and a characteristic tremor, are associated with loss of dopaminergic neurones in the substantia nigra of the brain. Genetic factors explain only a minority of cases, and a common toxic environmental insult remains elusive.