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Gastric synucleinopathy as prodromal pathological biomarker in idiopathic REM sleep behaviour disorder
  1. Chaewon Shin1,2,
  2. Sung-Hye Park3,4,
  3. Jung Hwan Shin5,
  4. Ji Young Yun6,
  5. Han-Kwang Yang7,8,
  6. Hyuk-Joon Lee7,8,
  7. Seong-Ho Kong7,8,
  8. Yun-Suhk Suh9,
  9. Tae-Beom Ahn10,
  10. Ki-Young Jung5,11,
  11. Jong-Min Kim11,12,
  12. Han-Joon Kim5,11,
  13. Beomseok Jeon5,11
  1. 1Department of Neurology, Chungnam National University, Daejeon, South Korea
  2. 2Department of Neurology, Chungnam National University Sejong Hospital, Sejong, South Korea
  3. 3Department of Pathology, College of Medicine, Seoul National University, Seoul, South Korea
  4. 4Department of Pathology, Seoul National University Hospital, Seoul, South Korea
  5. 5Department of Neurology, Seoul National University Hospital, Seoul, South Korea
  6. 6Department of Neurology, Ewha Womans University Seoul Hospital, Seoul, South Korea
  7. 7Department of Surgery, College of Medicine, Seoul National University, Seoul, South Korea
  8. 8Department of Surgery, Seoul National University Hospital, Seoul, South Korea
  9. 9Department of Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea
  10. 10Department of Neurology, Kyung Hee University Hospital, Seoul, South Korea
  11. 11Department of Neurology, College of Medicine, Seoul National University, Seoul, South Korea
  12. 12Department of Neurology, Seoul National University Bundang Hospital, Seongnam, South Korea
  1. Correspondence to Dr Beomseok Jeon, Department of Neurology, Seoul National University Hospital, Jongno-gu 03080, Korea (the Republic of); brain{at}snu.ac.kr

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Introduction

Pathological studies on peripheral tissues have been conducted in patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD) to investigate potential prodromal biomarkers before the development of overt synucleinopathies (online supplemental table 1). However, no studies have evaluated the in vivo tissues of the upper gastrointestinal (GI) tract in the iRBD population. Moreover, methodological heterogeneity makes it difficult to directly compare the results of each study on peripheral synucleinopathy. To address this problem, researchers who study tissues of the GI tract conducted an international collaborative study which showed that one immunohistochemistry (IHC) method showed 100% accuracy.1 This method is promising for unifying the method used in studies of the GI tract, but it has not yet been validated by other research groups.

Supplemental material

[jnnp-2020-324743supp001.pdf]

Therefore, the objectives of this study were (1) to evaluate the possibility of using upper GI specimens as a ‘prodromal’ pathological biomarker of synucleinopathy in patients with iRBD and (2) to validate the suggested staining method using full-depth surgical specimens.

Methods

We evaluated upper and lower marginal blocks of the upper GI tract in the same way as in our previous study2 from eight patients with polysomnography-confirmed iRBD and matched controls selected by eligibility criteria (online supplemental table 2). After validation staining of the positive and negative control tissues using the suggested method 5 (hereafter called method 1),1 we decided to use both method 1 and the staining method in our previous GI study (hereafter called method 2; online supplemental table 3).2 Adjacent sections were stained using neurofilament IHC to confirm neural structures.2 Experienced raters (S-HP and CS) who were anonymised to the clinical information and staining methods evaluated the pathological findings. When two phosphorylated alpha-synuclein (pAS) staining methods showed discordant results, we further stained adjacent 5 µm sections of the GI …

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Footnotes

  • Twitter @shparknp@snu.ac.kr

  • Contributors Study concept and design, drafting the manuscript: CS and BJ. Data acquisition: CS, S-HP, H-KY, H-JL, S-HK and Y-SS. Data analysis: CS, S-HP, JYY, JHS, T-BA, K-YJ, J-MK and H-JK. Review and revise the manuscript: all authors.

  • Funding This study was supported by research grants from Seoul National University Hospital (No. 0420180450), Chungnam National University Hospital (No. 2019-1572-01), and the National Research Foundation of Korea (No. 2018R1D1A1B07041440).

  • Competing interests CS received travel grants from the Korea Research-Based Pharmaceutical Industry Association, Korean Pharmaceutical Manufacturers Association, and National Research Foundation of Korea; and research grants from the National Research Foundation of Korea and Chungnam National University. JHS received a travel grant from the International Parkinson and Movement Disorder Society. S-HK received research grants from Medtronic Co., National Research Foundation of Korea, Korea Evaluation Institute of Industrial Technology, and Seoul National University. T-BA received travel grants from the Korea Research-Based Pharmaceutical Industry Association, Korean Pharmaceutical Manufacturers Association, and National Research Foundation of Korea. T-BA received an honorarium and travel grant from Yuhan Co. H-JK has received travel grants from the International Parkinson and Movement Disorder Society and Korean Movement Disorder Society; and research grants from the Seoul National University Hospital, New York University, and C-TRI. BJ received grants from the International Parkinson and Movement Disorder Society, Peptron and Abbvie Korea.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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