title: Quantifying rigidity of Parkinson's disease in relation to laxative treatment: a service evaluation.
abstract: To estimate whether laxatives prescribed for constipation in Parkinson's disease (PD) could moderate rigidity. Constipation predates diagnosis of PD by decades. Deposition of misfolded protein may begin in the gut, driven by dysbiosis. Successive antimicrobial exposures are associated with cumulative increase in rigidity, and rigidity has biological gradients on circulating leukocyte-subset counts.
  
  
  
  Retrospective service evaluation, in a gut/brain axis clinic, yielded an interrupted time series, relating maintenance laxative and other medication to rigidity, in consecutive outpatients identified by inclusion and exclusion criteria. Objective assessment of rigidity was used to bring greater sensitivity to change, validated against subjective gold standard (UPDRS).
  
  
  
  There were 1493 measurements of torque required to extend (flexor rigidity) and flex (extensor rigidity) the forearm in 79 PD patients over 374 person-years. Both were strongly associated with UPDRS (P < 0.001 and P = 0.008, respectively). Before exhibition of laxative, flexor rigidity increased by 6% (95% CI 1, 10) per year, plateauing at -2% (-4, 1) per year after, with no shift at initiation. Change in slope was significant (P = 0.002), and manifest in those naïve to antiparkinsonian 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).
  
  
  
  Maintenance laxative usage was associated with apparent stemming of the temporal increase in rigidity in PD, adding to indicative evidence of a continuing role of gastrointestinal dysbiosis in pathogenesis.
authors.affiliation: Institute of Pharmaceutical Science, King's College London, London, SE1 9NH, UK.|The Maudsley Hospital, London, SE5 8AZ, UK.
authors.forename: Aisha D
authors.initials: AD
authors.lastname: Augustin
authors.affiliation: Institute of Pharmaceutical Science, King's College London, London, SE1 9NH, UK.|Statistics Unit, Centre for Infectious Disease Surveillance and Control, Public Health England, London, NW9 5EQ, UK.
authors.forename: André
authors.initials: A
authors.lastname: Charlett
authors.affiliation: Institute of Pharmaceutical Science, King's College London, London, SE1 9NH, UK.
authors.forename: Clive
authors.initials: C
authors.lastname: Weller
authors.affiliation: Institute of Pharmaceutical Science, King's College London, London, SE1 9NH, UK.|The Maudsley Hospital, London, SE5 8AZ, UK.|Department of Gastroenterology, King's College Hospital, London, SE5 9RS, UK.
authors.forename: Sylvia M
authors.initials: SM
authors.lastname: Dobbs
authors.affiliation: Institute of Pharmaceutical Science, King's College London, London, SE1 9NH, UK.|The Maudsley Hospital, London, SE5 8AZ, UK.
authors.forename: David
authors.initials: D
authors.lastname: Taylor
authors.affiliation: Department of Gastroenterology, King's College Hospital, London, SE5 9RS, UK.
authors.forename: Ingvar
authors.initials: I
authors.lastname: Bjarnason
authors.affiliation: Institute of Pharmaceutical Science, King's College London, London, SE1 9NH, UK.|The Maudsley Hospital, London, SE5 8AZ, UK.|Department of Gastroenterology, King's College Hospital, London, SE5 9RS, UK.
authors.forename: R John
authors.initials: RJ
authors.lastname: Dobbs
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use; D003248:Constipation / Q000188:drug therapy* / Q000209:etiology; D064806:Dysbiosis / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D006801:Humans; D065186:Interrupted Time Series Analysis; D054368:Laxatives / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D017510:Protein Folding; D012189:Retrospective Studies
chemical_list: D000978:Antiparkinson Agents; D054368:Laxatives
keywords: bulk; dysbiosis of Parkinson's disease; enterokinetic and quanylate cyclase-C receptor agonist; gut/brain axis clinic; laxatives for constipation; objective quantification rigidity