Helicobacter hypothesis for idiopathic parkinsonism: Before and beyond

R. John Dobbs, Sylvia M. Dobbs, Clive Weller, Andre Charlett, Ingvar T. Bjarnason, Alan Curry, David S. Ellis, Mohammad A.A. Ibrahim, Maria V. McCrossan, John O'Donohue, Robert J. Owen, Norman L. Oxlade, Ashley B. Price, Jeremy D. Sanderson, Malur Sudhanva, John Williams

Research output: Contribution to journalReview articlepeer-review

59 Citations (Scopus)

Abstract

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. Similar benefit on brady/hypokinesia from eradicating "low-density" infection favors autoimmunity. Although a minority of UK probands are urea breath test positive for Helicobacter, the predicted probability of having the parkinsonian label depends on the serum H. pylori antibody profile, with clinically relevant gradients between this "discriminant index" and disease burden and progression. In IP, H. pylori antibodies discriminate for persistently abnormal bowel function, and specific abnormal duodenal enterocyte mitochondrial morphology is described in relation to H. pylori infection. Slow intestinal transit manifests as constipation from the prodrome. Diarrhea may flag secondary small-intestinal bacterial overgrowth. This, coupled with genetically determined intense inflammatory response, might explain evolution from brady/hypokinetic to rigidity-predominant parkinsonism.

Original languageEnglish
Pages (from-to)309-322
Number of pages14
JournalHelicobacter
Volume13
Issue number5
DOIs
Publication statusPublished - Oct 2008

Keywords

  • Aetiology
  • Helicobacter
  • Mitochrondria
  • Parkinson's Disease
  • Pathogenesis
  • Small-intestinal baterial overgrowth
  • Virus

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