Leukocyte-subset counts in idiopathic parkinsonism provide clues to a pathogenic pathway involving small intestinal bacterial overgrowth. A surveillance study

Dobbs R, Charlett André, Dobbs, Weller Clive, A, Iguodala Owens, Smee Cori, Plant J, Lawson, Taylor David, Bjarnason Ingvar

Description

Following Helicobacter pylori eradication in idiopathic parkinsonism (IP), hypokinesia improved but flexor-rigidity increased. Small intestinal bacterial-overgrowth (SIBO) is a candidate driver of the rigidity: hydrogen-breath-test-positivity is common in IP and case histories suggest that Helicobacter keeps SIBO at bay. Methods In a surveillance study, we explore relationships of IP-facets to peripheral immune/inflammatory-activation, in light of presence/absence of Helicobacter infection (urea-breath- and/or stool-antigen-test: positivity confirmed by gastric-biopsy) and hydrogen-breath-test status for SIBO (positivity: >20 ppm increment, 2 consecutive 15-min readings, within 2h of 25G lactulose). We question whether any relationships found between facets and blood leukocyte subset counts stand in patients free from anti-parkinsonian drugs, and are robust enough to defy fluctuations in performance consequent on short t½ therapy. Results Of 51 IP-probands, 36 had current or past Helicobacter infection on entry, 25 having undergone successful eradication (median 3.4 years before). Thirty-four were hydrogen-breath-test-positive initially, 42 at sometime (343 tests) during surveillance (2.8 years). Hydrogen-breath-test-positivity was associated inversely with Helicobacter -positivity (OR 0.20 (95% CI 0.04, 0.99), p<0.05). In 38 patients (untreated (17) or on stable long-t½ IP-medication), the higher the natural-killer count, the shorter stride, slower gait and greater flexor-rigidity (by mean 49 (14, 85) mm, 54 (3, 104) mm.s -1 , 89 (2, 177) Nm.10 -3 , per 100 cells.μl -1 increment, p=0.007, 0.04 & 0.04 respectively, adjusted for patient characteristics). T-helper count was inversely associated with flexor-rigidity before (p=0.01) and after adjustment for natural-killer count (-36(-63, -10) Nm.10 -3 per 100 cells.μl -1 , p =0.007). Neutrophil count was inversely associated with tremor (visual analogue scale, p=0.01). Effect-sizes were independent of IP-medication, and not masked by including 13 patients receiving levodopa (except natural-killer count on flexor-rigidity). Cellular associations held after allowing for potentially confounding effect of hydrogen-breath-test or Helicobacter status. Moreover, additional reduction in stride and speed (68 (24, 112) mm & 103 (38, 168) mm.s -1 , each p=0.002) was seen with .

Sujets

• Helicobacter
• Small bowel bacterial overgrowth syndrome
• T helper cell
• Neutrophil granulocyte
• Hypokinesia
• Rigidity
• Trémor

Informations

• Publié par: biomed
• Publié le: 01 janvier 2012
• Nombre de lectures: 15
• Langue: English

Extrait

Dobbset al. Gut Pathogens2012,4:12 http://www.gutpathogens.com/content/4/1/12

R E S E A R C HOpen Access Leukocytesubset counts in idiopathic parkinsonism provide clues to a pathogenic pathway involving small intestinal bacterial overgrowth. A surveillance study 1,2,3 1,41,2,3* 15 R John Dobbs, André Charlett, Sylvia M Dobbs, Clive Weller , Mohammad A A Ibrahim , 2 22 61,2 3 Owens Iguodala , Cori Smee , J Malcolm Plant , Andrew J Lawson , David Taylorand Ingvar Bjarnason

Abstract Background:FollowingHelicobacter pylorieradication in idiopathic parkinsonism (IP), hypokinesia improved but flexorrigidity increased. Small intestinal bacterialovergrowth (SIBO) is a candidate driver of the rigidity: hydrogen breathtestpositivity is common in IP and case histories suggest thatHelicobacterkeeps SIBO at bay. Methods:In a surveillance study, we explore relationships of IPfacets to peripheral immune/inflammatory activation, in light of presence/absence ofHelicobacterinfection (ureabreath and/or stoolantigentest: positivity confirmed by gastricbiopsy) and hydrogenbreathtest status for SIBO (positivity: >20 ppm increment, 2 consecutive 15min readings, within 2h of 25G lactulose). We question whether any relationships found between facets and blood leukocyte subset counts stand in patients free from antiparkinsonian drugs, and are robust enough to defy fluctuations in performance consequent on short t½ therapy. Results:Of 51 IPprobands, 36 had current or pastHelicobacterinfection on entry, 25 having undergone successful eradication (median 3.4 years before). Thirtyfour were hydrogenbreathtestpositive initially, 42 at sometime (343 tests) during surveillance (2.8 years). Hydrogenbreathtestpositivity was associated inversely withHelicobacter positivity (OR 0.20 (95% CI 0.04, 0.99), p<0.05). In 38 patients (untreated (17) or on stable longt½ IPmedication), the higher the naturalkiller count, the shorter 1 3 stride, slower gait and greater flexorrigidity (by mean 49 (14, 85) mm, 54 (3, 104) mm.s, 89 (2, 177) Nm.10, per 1 100 cells.μl increment,p=0.007, 0.04 & 0.04 respectively, adjusted for patient characteristics). Thelper count was inversely associated with flexorrigidity before (p=0.01) and after adjustment for naturalkiller count (36(63, 10) 3 1 Nm.10 per100 cells.μl ,p=0.007). Neutrophil count was inversely associated with tremor (visual analogue scale, p=0.01). Effectsizes were independent of IPmedication, and not masked by including 13 patients receiving levodopa (except naturalkiller count on flexorrigidity). Cellular associations held after allowing for potentially confounding effect of hydrogenbreathtest orHelicobacterstatus. Moreover, additional reduction in stride and 1 speed (68 (24, 112) mm & 103 (38, 168)mm.s ,each p=0.002) was seen withHelicobacterpositivity. Hydrogen breathtestpositivity, itself, was associated with higher naturalkiller and Thelper counts, lower neutrophils (p=0.005, 0.02 & 0.008). (Continued on next page)

* Correspondence: [e-mail] 1 Pharmaceutical Science, King's College London, FranklinWilkins Building, 150 Stamford Street, London SE1 9NH, UK Full list of author information is available at the end of the article

© 2012 Dobbs et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.