REM sleep behavior disorder is related to enteric neuropathology in Parkinson disease

Neurology. 2017 Oct 10;89(15):1612-1618. doi: 10.1212/WNL.0000000000004496. Epub 2017 Sep 8.

Abstract

Objective: To determine whether REM sleep behavior disorder (RBD) in Parkinson disease (PD) is associated with lesions and dysfunctions of the autonomic nervous system by evaluating enteric phosphorylated α-synuclein histopathology (PASH) and permeability.

Methods: A total of 45 patients with PD were included in this cross-sectional study. RBD was diagnosed on the basis of a standardized clinical interview and confirmed by polysomnography. For each patient, 5 biopsies were taken at the junction between the sigmoid and descending colon during the course of a rectosigmoidoscopy. For the detection of enteric PASH, 2 colonic biopsies were analyzed by immunohistochemistry with antibodies against phosphorylated α-synuclein and PGP9.5 in 43 patients (2 patients were excluded because only 1 biopsy was available). The paracellular permeability and transcellular permeability were evaluated by measuring sulfonic acid and horseradish peroxidase flux, respectively, in the 3 remaining biopsies mounted in Ussing chambers.

Results: Enteric PASH was more frequent in the subgroup of patients with PD with RBD compared to patients without RBD (18 of 28, 64.3%, vs 2 of 15, 13.3%, respectively, p < 0.01). No differences were observed in intestinal permeability between patients with PD with and without RBD.

Conclusions: Patients with PD and RBD have a greater frequency of synuclein pathology in the enteric nervous system, suggesting that RBD is associated with widespread synuclein neuropathology.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cell Membrane Permeability / physiology
  • Colonoscopy
  • Cross-Sectional Studies
  • Enteric Nervous System / metabolism
  • Enteric Nervous System / pathology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Parkinson Disease / complications*
  • REM Sleep Behavior Disorder / etiology*
  • Retrospective Studies
  • Severity of Illness Index
  • alpha-Synuclein / metabolism

Substances

  • alpha-Synuclein