Helicobacter Hypothesis for Idiopathic Parkinsonism: Before and Beyond
Identifieur interne : 001A74 ( Istex/Curation ); précédent : 001A73; suivant : 001A75Helicobacter Hypothesis for Idiopathic Parkinsonism: Before and Beyond
Auteurs : R. John Dobbs [Royaume-Uni] ; Sylvia M. Dobbs [Royaume-Uni] ; Clive Weller [Royaume-Uni] ; André Charlett [Royaume-Uni] ; Ingvar T. Bjarnason ; Alan Curry [Royaume-Uni] ; David S. Ellis ; Mohammad A. A. Ibrahim ; Maria V. Mccrossan ; John O'Donohue ; Robert J. Owen [Royaume-Uni] ; Norman L. Oxlade [Royaume-Uni] ; Ashley B. Price [Royaume-Uni] ; Jeremy D. Sanderson [Royaume-Uni] ; Malur Sudhanva [Royaume-Uni] ; John Williams [Royaume-Uni]Source :
- Helicobacter [ 1083-4389 ] ; 2008-10.
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.
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DOI: 10.1111/j.1523-5378.2008.00622.x
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Ingvar T. Bjarnason<affiliation><mods:affiliation>Departments of Gastroenterology and</mods:affiliation><wicri:noCountry code="no comma">Departments of Gastroenterology and</wicri:noCountry></affiliation><affiliation><mods:affiliation>Electronmicroscopy and</mods:affiliation><wicri:noCountry code="no comma">Electronmicroscopy and</wicri:noCountry></affiliation><affiliation><mods:affiliation>Immunology, and</mods:affiliation><wicri:noCountry code="subField">and</wicri:noCountry></affiliation><affiliation><mods:affiliation>Electronmicroscopy and</mods:affiliation><wicri:noCountry code="no comma">Electronmicroscopy and</wicri:noCountry></affiliation><affiliation><mods:affiliation>Departments of Gastroenterology and</mods:affiliation><wicri:noCountry code="no comma">Departments of Gastroenterology and</wicri:noCountry></affiliation>Le document en format XML
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John" last="Dobbs">R. John Dobbs</name><affiliation wicri:level="1"><mods:affiliation>Section of Clinical Neuropharmacology, Institute of Psychiatry, King's College London, London, UK;</mods:affiliation><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Section of Clinical Neuropharmacology, Institute of Psychiatry, King's College London, London</wicri:regionArea></affiliation><affiliation><mods:affiliation>Departments of Gastroenterology and</mods:affiliation></affiliation></author><author><name sortKey="Dobbs, Sylvia M" sort="Dobbs, Sylvia M" uniqKey="Dobbs S" first="Sylvia M." last="Dobbs">Sylvia M. Dobbs</name><affiliation wicri:level="1"><mods:affiliation>Section of Clinical Neuropharmacology, Institute of Psychiatry, King's College London, London, UK;</mods:affiliation><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Section of Clinical Neuropharmacology, Institute of Psychiatry, King's College London, London</wicri:regionArea></affiliation><affiliation><mods:affiliation>Departments of Gastroenterology and</mods:affiliation></affiliation></author><author><name sortKey="Weller, Clive" sort="Weller, Clive" uniqKey="Weller C" first="Clive" last="Weller">Clive Weller</name><affiliation wicri:level="1"><mods:affiliation>Section of Clinical Neuropharmacology, Institute of Psychiatry, King's College London, London, UK;</mods:affiliation><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Section of Clinical Neuropharmacology, Institute of Psychiatry, King's College London, London</wicri:regionArea></affiliation></author><author><name sortKey="Charlett, Andre" sort="Charlett, Andre" uniqKey="Charlett A" first="André" last="Charlett">André Charlett</name><affiliation wicri:level="1"><mods:affiliation>Section of Clinical Neuropharmacology, Institute of Psychiatry, King's College London, London, UK;</mods:affiliation><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Section of Clinical Neuropharmacology, Institute of Psychiatry, King's College London, London</wicri:regionArea></affiliation><affiliation><mods:affiliation>Statistics Unit and</mods:affiliation></affiliation></author><author><name sortKey="Bjarnason, Ingvar T" sort="Bjarnason, Ingvar T" uniqKey="Bjarnason I" first="Ingvar T." last="Bjarnason">Ingvar T. Bjarnason</name><affiliation><mods:affiliation>Departments of Gastroenterology and</mods:affiliation><wicri:noCountry code="no comma">Departments of Gastroenterology and</wicri:noCountry></affiliation></author><author><name sortKey="Curry, Alan" sort="Curry, Alan" uniqKey="Curry A" first="Alan" last="Curry">Alan Curry</name><affiliation wicri:level="1"><mods:affiliation>Electronmicroscopy, Health Protection Agency North‐West, Manchester, UK;</mods:affiliation><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Electronmicroscopy, Health Protection Agency North‐West, Manchester</wicri:regionArea></affiliation></author><author><name sortKey="Ellis, David S" sort="Ellis, David S" uniqKey="Ellis D" first="David S." last="Ellis">David S. Ellis</name><affiliation><mods:affiliation>Electronmicroscopy and</mods:affiliation><wicri:noCountry code="no comma">Electronmicroscopy and</wicri:noCountry></affiliation></author><author><name sortKey="Ibrahim, Mohammad A A" sort="Ibrahim, Mohammad A A" uniqKey="Ibrahim M" first="Mohammad A. A." last="Ibrahim">Mohammad A. A. Ibrahim</name><affiliation><mods:affiliation>Immunology, and</mods:affiliation><wicri:noCountry code="subField">and</wicri:noCountry></affiliation></author><author><name sortKey="Mccrossan, Maria V" sort="Mccrossan, Maria V" uniqKey="Mccrossan M" first="Maria V." last="Mccrossan">Maria V. Mccrossan</name><affiliation><mods:affiliation>Electronmicroscopy and</mods:affiliation><wicri:noCountry code="no comma">Electronmicroscopy and</wicri:noCountry></affiliation></author><author><name sortKey="O Donohue, John" sort="O Donohue, John" uniqKey="O Donohue J" first="John" last="O'Donohue">John O'Donohue</name><affiliation><mods:affiliation>Departments of Gastroenterology and</mods:affiliation><wicri:noCountry code="no comma">Departments of Gastroenterology and</wicri:noCountry></affiliation></author><author><name sortKey="Owen, Robert J" sort="Owen, Robert J" uniqKey="Owen R" first="Robert J." last="Owen">Robert J. Owen</name><affiliation wicri:level="1"><mods:affiliation>Helicobacter Reference Unit, Health Protection Agency, London, UK;</mods:affiliation><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Helicobacter Reference Unit, Health Protection Agency, London</wicri:regionArea></affiliation></author><author><name sortKey="Oxlade, Norman L" sort="Oxlade, Norman L" uniqKey="Oxlade N" first="Norman L." last="Oxlade">Norman L. Oxlade</name><affiliation wicri:level="1"><mods:affiliation>Section of Clinical Neuropharmacology, Institute of Psychiatry, King's College London, London, UK;</mods:affiliation><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Section of Clinical Neuropharmacology, Institute of Psychiatry, King's College London, London</wicri:regionArea></affiliation></author><author><name sortKey="Price, Ashley B" sort="Price, Ashley B" uniqKey="Price A" first="Ashley B." last="Price">Ashley B. Price</name><affiliation wicri:level="1"><mods:affiliation>Department of Histopathology, Northwick Park and St. Mark's Hospitals, London, UK;</mods:affiliation><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Department of Histopathology, Northwick Park and St. Mark's Hospitals, London</wicri:regionArea></affiliation></author><author><name sortKey="Sanderson, Jeremy D" sort="Sanderson, Jeremy D" uniqKey="Sanderson J" first="Jeremy D." last="Sanderson">Jeremy D. Sanderson</name><affiliation wicri:level="1"><mods:affiliation>Department of Gastroenterology, Guy's and St Thomas's Hospital, London, UK</mods:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Gastroenterology, Guy's and St Thomas's Hospital, London</wicri:regionArea></affiliation></author><author><name sortKey="Sudhanva, Malur" sort="Sudhanva, Malur" uniqKey="Sudhanva M" first="Malur" last="Sudhanva">Malur Sudhanva</name><affiliation wicri:level="1"><mods:affiliation>South London Specialist Virology Centre, Health Protection Agency Regional Laboratory, Kings College Hospital, London, UK;</mods:affiliation><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>South London Specialist Virology Centre, Health Protection Agency Regional Laboratory, Kings College Hospital, London</wicri:regionArea></affiliation></author><author><name sortKey="Williams, John" sort="Williams, John" uniqKey="Williams J" first="John" last="Williams">John Williams</name><affiliation wicri:level="1"><mods:affiliation>Diagnostic Parasitology, London School of Hygiene and Tropical Medicine, London, UK;</mods:affiliation><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Diagnostic Parasitology, London School of Hygiene and Tropical Medicine, London</wicri:regionArea></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Helicobacter</title><title level="j" type="alt">HELICOBACTER</title><idno type="ISSN">1083-4389</idno><idno type="eISSN">1523-5378</idno><imprint><biblScope unit="vol">13</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="309">309</biblScope><biblScope unit="page" to="322">322</biblScope><biblScope unit="page-count">14</biblScope><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2008-10">2008-10</date></imprint><idno type="ISSN">1083-4389</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1083-4389</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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