Blood profile holds clues to role of infection in a premonitory state for idiopathic parkinsonism and of gastrointestinal infection in established disease

• Main Authors: Charlett André, Dobbs R John, Dobbs Sylvia M, Weller Clive, Ibrahim Mohammad AA, Dew Tracy, Sherwood Roy, Oxlade Norman L, Plant J Malcolm, Bowthorpe James, Lawson Andrew J, Curry Alan, Peterson Dale W, Bjarnason Ingvar T
• Format: Article
• Language: English
• Published: BMC 2009-11-01
• Series: Gut Pathogens
• Online Access: http://www.gutpathogens.com/content/1/1/20

<p>Abstract</p> <p>The two-stage neuroinflammatory process, containment and progression, proposed to underlie neurodegeneration may predicate on systemic inflammation arising from the gastrointestinal tract. <it>Helicobacter </it>infection has been described as one switch in the pathogenic-circuitry of idiopathic parkinsonism (IP): eradication modifies disease progression and marked deterioration accompanies eradication-failure. Moreover, serum <it>Helicobacter</it>-antibody-profile predicts presence, severity and progression of IP. Slow gastrointestinal-transit precedes IP-diagnosis and becomes increasingly-apparent after, predisposing to small-intestinal bacterial-overgrowth (SIBO). Although IP is well-described as a systemic illness with a long prodrome, there has been no comprehensive overview of the blood profile. Here, it is examined in relation to <it>Helicobacter </it>status and lactulose-hydrogen-breath-testing for SIBO.</p> <p>A robust finding of reduced lymphocyte count in 126 IP-probands and 79 spouses (without clinically-definite IP), compared with that in 381 controls (p < 0.001 in each case), was not explained by <it>Helicobacter</it>-status or breath-hydrogen. This complements a previous report that spouses were 'down-the-pathway' to 'clinically-definite' disease. In 205 other controls without clinically-definite IP, there were strong associations between sporadic cardinal features and immunoglobulin class concentration, not explained by <it>Helicobacter</it>-status. Premonitory states for idiopathic parkinsonism associated with relative lymphopenia, higher serum immunoglobulin concentrations and evidence of enteric-nervous-system damage may prove viral in origin.</p> <p>Although only 8% of the above 79 spouses were urea-breath-test-positive for <it>Helicobacter</it>, all 8 spouses with clinically-definite IP were (p < 0.0001). Transmission of a 'primer' to a <it>Helicobacter</it>-colonised recipient might result in progression to the diagnostic threshold.</p> <p>Twenty-five percent of the 126 probands were seropositive for anti-nuclear autoantibody. In 20 probands, monitored before and serially after anti-<it>Helicobacter </it>therapy, seropositivity marked a severe hypokinetic response (p = 0.03). It may alert to continuing infection, even at low-density. Hyperhomocysteinemia is a risk factor for dementia and depression. Serum homocysteine exceeded the target in 43% of the 126 IP-probands. It was partially explained by serum B12 (12% variance, p < 0.001), but not by <it>Helicobacter</it>-status (gastric-atrophy uncommon in IP) or levodopa treatment. Immune-inflammatory activation increases homocysteine production. Since an estimated 60% of probands are hydrogen-breath-test positive, SIBO, with its increased bacterial utilisation of B12, is a likely cause. Thus, two prognostic indicators in established IP fit with involvement of <it>Helicobacter </it>and SIBO.</p>