Differential Effect of Helicobacter pylori Eradication on Time‐Trends in Brady/Hypokinesia and Rigidity in Idiopathic Parkinsonism

Abstract

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. We report on study completion in all 30 who had commenced post-treatment assessments.Methods:This is a randomized, placebo-controlled, parallel-group efficacy study of eradicating biopsy-proven (culture and/or organism on histopathology) Helicobacter pylori infection on the time course of facets of IP, in probands taking no, or stable long-t½, anti-parkinsonian medication. Persistent infection at de-blinding (scheduled 1-year post-treatment) led to open active eradication-treatment.Results:Stride length improved (73 (95% CI 14–131) mm/year, p = .01) in favor of “successful” blinded active over placebo, irrespective of anti-parkinsonian medication, and despite worsening upper limb flexor rigidity (237 (57–416) Nm × 10−3/year, p = .01). This differential effect was echoed following open active, post-placebo. Gait did not deteriorate in year 2 and 3 post-eradication. Anti-nuclear antibody was present in all four proven (two by molecular microbiology only) eradication failures. In the remainder, it marked poorer response during the year after eradication therapy, possibly indicating residual “low-density” infection.We illustrate the importance of eradicating low-density infection, detected only by molecular microbiology, in a proband not receiving anti-parkinsonian medication. Stride length improved (424 (379–468) mm for 15 months post-eradication, p = .001), correction of deficit continuing to 3.4 years. Flexor rigidity increased before hydrogen-breath-test positivity for small intestinal bacterial overgrowth (208 (28–388) Nm × 10−3, p = .02), increased further during (171 (67–274), p = .001) (15–31 months), and decreased (136 (6–267), p = .04) after restoration of negativity (32–41 months).Conclusion:Helicobacter is an arbiter of progression, independent of infection-load.

Towards Defining a Rigidity-Associated Pathogenic Pathway in Idiopathic Parkinsonism

“…A case study supports the candidature of overgrowth as a driver of rigidity [5] . Following H. pylori eradication, rigidity worsened in relation to onset of hydrogen breath test positivity, and improved on regaining negativity.…”

“…Improvement in gait brady/hypokinesia following the successful blinded active treatment for H. pylori was mirrored by worsening of objectively measured upper limb flexor rigidity [5] . Rigidity worsened in year 1 with no further change over years 2 and 3.…”

“…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.…”

Helicobacter pylori infection is associated with worse severity of Parkinson's disease

“…However, only two studies [19,23] attempted to correlate, in a cross-sectional manner, the presence of HP infection with worse PD severity. These studies were limited by small sample size [18e20, 22,23], open-label design [19,20,22], and/or the use of non-validated assessments of motor function [17,21,23]; several have been reported in abstract form only [20,22,23]. Thus, a recent Cochrane review concluded that further studies are required to address the gaps in knowledge regarding the role of HP infection in PD [24], and screening PD patients for HP status has yet to enter routine clinical practice.…”

High prevalence of Helicobacter pylori infection in Malaysian Parkinson's disease patients

“…3 Cycad is known to cause amyotrophic lateral sclerosis/parkinsonism-dementia complex among populations in Guam 4,5 and Japan's Kii Peninsula. 6 Studies have shown that H. pylori infection leads to poorer motor function, 7,8 and eradication leads to improvement in stride length. 7 Eradication of H. pylori also correlated with a reduction in inflammatory markers, 9,10 leading some authors to hypothesize that H. pylori infection leads to a chronic inflammatory process resulting in the destruction of dopaminergic neurons.…”