Differential Effect of Helicobacter pylori Eradication on Time‐Trends in Brady/Hypokinesia and Rigidity in Idiopathic Parkinsonism |
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| Authors: | Sylvia M Dobbs R John Dobbs Clive Weller André Charlett Ingvar T Bjarnason Andrew J Lawson Darren Letley Lucy Harbin Ashley B Price Mohammad A A Ibrahim Norman L Oxlade James Bowthorpe Daniel Leckstroem Cori Smee J Malcolm Plant Dale W Peterson |
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| Institution: | 1. Psychological Medicine and Pharmaceutical Sciences, King’s College London, London, UK;2. Department of Gastroenterology, Guy’s, King’s, St Thomas’ School of Medicine, London, UK;3. Statistics Unit, Health Protection Agency, London, UK;4. Laboratory of Gastrointestinal Pathogens, Health Protection Agency, London, UK;5. Nottingham Digestive Diseases Centre Biomedical Research Unit, University Hospital, Nottingham, UK;6. Department of Histopathology, Northwick Park and St. Mark’s Hospitals, Imperial College, London, UK;7. Department of Immunology, Guy’s, King’s, St Thomas’ School of Medicine, London, UK;8. School of Life Sciences, University of Hertfordshire, Hatfield, Hertfordshire, UK |
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| 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. |
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| Keywords: | H pylori eradication idiopathic parkinsonism treatment failure anti‐nuclear antibody low‐density infection small intestinal bacterial overgrowth |
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