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Quantifying rigidity of Parkinson's disease in relation to laxative treatment: A service evaluation

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Original languageEnglish
Pages (from-to)441–450
JournalBritish Journal of Clinical Pharmacology
Volume82
Issue number2
Early online date21 May 2016
DOIs
Accepted/In press4 Apr 2016
E-pub ahead of print21 May 2016
PublishedAug 2016

Bibliographical note

WHAT IS KNOWN ABOUT THIS SUBJECT Constipation markedly affects quality-of-life in Parkinson’s disease (PD), and predates diagnosis by decades. Majority of PD patients have small-intestinal-bacterial-overgrowth at presentation, probably a consequence of caeco-ileal reflux. There are biological gradients of quantified rigidity on circulating inflammatory markers: improving transit may protect. WHAT THIS STUDY ADDS Flexor-rigidity increased by a clinically-significant amount year-on-year before exhibition of maintenance laxatives, plateauing after. Similar pattern seen with bulk, osmotic and enterokinetic laxatives, pointing to common mechanism. In contrast, linaclotide, which increases gastrointestinal-secretion, was associated with a large step-down in rigidity.

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Abstract

AIM: To estimate whether laxatives prescribed for constipation in Parkinson’s disease (PD) could moderate rigidity. Constipation pre-dates diagnosis of PD by decades. Deposition of misfolded-protein may begin in gut, driven by dysbiosis. Successive antimicrobial exposures are associated with cumulative increase in rigidity, and rigidity has biological gradients on circulating leucocyte-subset counts. METHODS: Retrospective service evaluation, in a gut/brain axis clinic, yielded an interrupted-time-series, relating maintenance laxative and other medication to rigidity, in consecutive out-patients identified by inclusion and exclusion criteria. Objective assessment of rigidity was used to bring greater sensitivity to change, validated against subjective gold-standard (UPDRS). RESULTS: There were 1493 measurements of torque required to extend (flexor-rigidity) and flex (extensor-rigidity) forearm in 79 PD-patients over 374 person-years. Both were strongly associated with UPDRS (P<0.001 & =0.008, respectively). Before exhibition of laxative, flexor-rigidity increased by 6 (95% CI 1, 10)% per year, plateauing during at -2 (-4, 1)% per year, with no shift at initiation. Change in slope was significant (P=0.002), and manifest in those naïve to anti-parkinsonian medication. The change was replicated for individual laxative classes (bulk, osmotic, enterokinetic). There was no temporal change in extensor-rigidity. Limited experience with a quanylate cyclase-C receptor agonist (17 patients, 6 person-years) indicated a large and significant step-down in flexor- and extensor-rigidity, of 19 (1, 34) and 16 (6, 24) respectively (P=0.04 and <0.001). CONCLUSIONS: Maintenance laxative usage was associated with apparent stemming the temporal increase in rigidity in PD, adding to indicative evidence of a continuing role of gastrointestinal dysbiosis in pathogenesis.

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