Helicobacter hypothesis for idiopathic parkinsonism: before and beyond.
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.
Dobbs
R John
RJ
Section of Clinical Neuropharmacology, Institute of Psychiatry, King's College London, London, UK. s.dobbs@iop.kcl.ac.uk or
Dobbs
Sylvia M
SM
Weller
Clive
C
Charlett
André
A
Bjarnason
Ingvar T
IT
Curry
Alan
A
Ellis
David S
DS
Ibrahim
Mohammad A A
MA
McCrossan
Maria V
MV
O'Donohue
John
J
Owen
Robert J
RJ
Oxlade
Norman L
NL
Price
Ashley B
AB
Sanderson
Jeremy D
JD
Sudhanva
Malur
M
Williams
John
J
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