Cutaneous autonomic pilomotor testing to unveil the role of neuropathy progression in early Parkinson's disease (CAPTURE PD): Protocol for a multicenter study

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Timo Siepmann - , Department of Neurology (Author)
  • Alexandra Pintér - , Semmelweis University (Author)
  • Sylvia J. Buchmann - , Harvard University, Charité – Universitätsmedizin Berlin (Author)
  • Leonie Stibal - , Harvard University (Author)
  • Martin Arndt - , Department of Neurology (Author)
  • Anne Sophie Kubasch - , Department of Paediatrics (Author)
  • Marie Luise Kubasch - , TUD Dresden University of Technology, Harvard University (Author)
  • Ana Isabel Penzlin - , Department of Neurology (Author)
  • Elka Frenz - , Department of Neurology (Author)
  • Wagner Zago - , Prothena Corporation (Author)
  • Tamás Horváth - , Budapest University of Technology and Economics (Author)
  • Szabolcs Szatmári - , Semmelweis University (Author)
  • Dániel Bereczki - , Semmelweis University (Author)
  • Annamária Takáts - , Semmelweis University (Author)
  • Tjalf Ziemssen - , Department of Neurology (Author)
  • Axel Lipp - , Charité – Universitätsmedizin Berlin (Author)
  • Roy Freeman - , Harvard University (Author)
  • Heinz Reichmann - , Department of Neurology (Author)
  • Kristian Barlinn - , Department of Neurology (Author)
  • Ben Min Woo Illigens - , Harvard University (Author)

Abstract

Background: In Parkinson's disease (PD), alpha-synuclein accumulation in cutaneous autonomic pilomotor and sudomotor nerve fibers has been linked to autonomic nervous system disturbances even in the early stages of the disease. This study aims to assess the association between alpha-synuclein-mediated structural autonomic nerve fiber damage and function in PD, elucidate the role of neuropathy progression during the early disease stages, and test reproducibility and external validity of pilomotor function assessment using quantitative pilomotor axon-reflex test and sudomotor function via quantitative direct and indirect test of sudomotor function. Methods/design: A prospective controlled study will be conducted at four study sites in Europe and the USA. Fifty-two male and female patients with idiopathic PD (Hoehn and Yahr 1-2) and 52 age- and sex-matched healthy controls will be recruited. Axon-reflex-mediated pilomotor erection will be induced by iontophoresis of phenylephrine on the dorsal forearm. Silicone impressions of the response will be obtained, scanned, and quantified for pilomotor muscle impressions by number, impression size, and area of axon-reflex spread. Axon-reflex-mediated sweating following acetylcholine iontophoresis will be quantified for number and size of droplets and axon-reflex spread. Sympathetic skin responses, autonomic and motor symptoms will be evaluated. Tests will be performed at baseline, after 2 weeks, 1, 2, and 3 years. Skin biopsies will be obtained at baseline and after 3 years and will be analyzed for nerve fiber density and alpha-synuclein accumulation. Discussion: We anticipate that progression of autonomic nerve dysfunction assessed via pilomotor and sudomotor axon-reflex tests is related to progression of autonomic symptom severity and alpha-synuclein deposition. Potential applications of the techniques include interventional studies evaluating disease-modifying approaches and clinical assessment of autonomic dysfunction in patients with PD.

Details

Original languageEnglish
Article number212
JournalFrontiers in neurology
Volume8
Issue numberMAY
Publication statusPublished - 26 May 2017
Peer-reviewedYes

External IDs

ORCID /0000-0001-8799-8202/work/171553404

Keywords

ASJC Scopus subject areas

Keywords

  • autonomic, Axon-reflex, Diagnosis, Parkinson's disease, Pilomotor