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. 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-t(1/2), 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 x 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 x 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).


CONCLUSIONS
Helicobacter is an arbiter of progression, independent of infection-load.
Dobbs
Sylvia M
SM
Psychological Medicine and Pharmaceutical Sciences, King's College London, London, UK. sylviadobbs@therapeuticsresearch.net
Dobbs
R John
RJ
Weller
Clive
C
Charlett
André
A
Bjarnason
Ingvar T
IT
Lawson
Andrew J
AJ
Letley
Darren
D
Harbin
Lucy
L
Price
Ashley B
AB
Ibrahim
Mohammad A A
MA
Oxlade
Norman L
NL
Bowthorpe
James
J
Leckstroem
Daniel
D
Smee
Cori
C
Plant
J Malcolm
JM
Peterson
Dale W
DW
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000897:Anti-Ulcer Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005684:Gait / Q000187:drug effects; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents