title: Helicobacter hypothesis for idiopathic parkinsonism: before and beyond.
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.
authors.affiliation: Section of Clinical Neuropharmacology, Institute of Psychiatry, King's College London, London, UK. s.dobbs@iop.kcl.ac.uk or
authors.forename: R John
authors.initials: RJ
authors.lastname: Dobbs
authors.forename: Sylvia M
authors.initials: SM
authors.lastname: Dobbs
authors.forename: Clive
authors.initials: C
authors.lastname: Weller
authors.forename: André
authors.initials: A
authors.lastname: Charlett
authors.forename: Ingvar T
authors.initials: IT
authors.lastname: Bjarnason
authors.forename: Alan
authors.initials: A
authors.lastname: Curry
authors.forename: David S
authors.initials: DS
authors.lastname: Ellis
authors.forename: Mohammad A A
authors.initials: MA
authors.lastname: Ibrahim
authors.forename: Maria V
authors.initials: MV
authors.lastname: McCrossan
authors.forename: John
authors.initials: J
authors.lastname: O'Donohue
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Owen
authors.forename: Norman L
authors.initials: NL
authors.lastname: Oxlade
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Price
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Sanderson
authors.forename: Malur
authors.initials: M
authors.lastname: Sudhanva
authors.forename: John
authors.initials: J
authors.lastname: Williams
mesh_terms: D000818:Animals; D016481:Helicobacter Infections / Q000150:complications*; D006801:Humans; D008928:Mitochondria / Q000473:pathology / Q000648:ultrastructure; D008954:Models, Biological; D010300:Parkinson Disease / Q000209:etiology* / Q000382:microbiology / Q000473:pathology