The two-stage neuroinflammatory process, containment and progression, proposed to underlie neurodegeneration may predicate on systemic
inflammation arising from the gastrointestinal tract.
Helicobacter 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 Helicobacter-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 Helicobacter status and
lactulose-
hydrogen-breath-testing for SIBO. 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 Helicobacter-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 Helicobacter-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.Although only 8% of the above 79 spouses were
urea-breath-test-positive for Helicobacter, all 8 spouses with clinically-definite IP were (p < 0.0001). Transmission of a 'primer' to a Helicobacter-colonised recipient might result in progression to the diagnostic threshold. Twenty-five percent of the 126 probands were seropositive for anti-nuclear
autoantibody. In 20 probands, monitored before and serially after anti-Helicobacter
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 Helicobacter-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 Helicobacter and SIBO.