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Research paper
Quantitative correlation between cardiac MIBG uptake and remaining axons in the cardiac sympathetic nerve in Lewy body disease
  1. Makoto Takahashi1,
  2. Masako Ikemura2,
  3. Teruaki Oka2,
  4. Toshiki Uchihara3,
  5. Koichi Wakabayashi4,
  6. Akiyoshi Kakita5,
  7. Hitoshi Takahashi5,
  8. Mari Yoshida6,
  9. Shuta Toru7,
  10. Takayoshi Kobayashi7,
  11. Satoshi Orimo1
  1. 1Department of Neurology, Kanto Central Hospital, Tokyo, Japan
  2. 2Division of Pathology, Kanto Central Hospital, Tokyo, Japan
  3. 3Laboratory of Structural Neuropathology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
  4. 4Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
  5. 5Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan
  6. 6Institute for Medical Science of Aging, Aichi Medical University, Nagakute, Japan
  7. 7Department of Neurology, Nakano General Hospital, Tokyo, Japan
  1. Correspondence to Dr Satoshi Orimo, Department of Neurology, Kanto Central Hospital, 6-25-1 Kami-Yoga, Setagaya-ku, Tokyo 158-8531, Japan; orimo{at}kanto-ctr-hsp.com

Abstract

Objectives Reduced cardiac meta-iodobenzylguanidine (MIBG) uptake and loss of cardiac sympathetic axons, as its possible anatomical substrate, were both recognised in Lewy body disease (LBD), while their direct correlation has so far remained speculative. Increasing availability of autopsy-confirmed cases of LBD prompted us to quantify residual cardiac sympathetic axons to establish their relationship to cardiac MIBG uptake.

Methods We collected cardiac tissue samples from 23 patients with autopsy-confirmed LBD and two non-LBD control patients who underwent 123I-MIBG cardiac scintigraphy in life. Samples of the left ventricular anterior wall were stained with anti-tyrosine hydroxylase (TH) and anti-neurofilament (NF) antibodies as markers of cardiac nerve axons. We quantified the immunolabelled areas and assessed their correlation to standardised heart to mediastinum (H/M) ratios of 123I-MIBG cardiac scintigraphy.

Results Cardiac MIBG uptake in the early and delayed phases was reduced in 90.9% and 95.7% of patients with LBD, respectively. The area of TH-immunoreactive axons correlated significantly with the H/M ratio in the early (p=0.036) as well as in the delayed (p=0.018) phases. The area of NF-immunoreactive axons also correlated with the H/M ratio in the early (p=0.003) as well as in the delayed (p=0.001) phases.

Conclusions Tight quantitative correlation between cardiac 123I-MIBG uptake and corresponding loss of sympathetic axons in LBD, as established for the first time by this study, provides a scientific basis to confirm the reliability of MIBG cardiac scintigraphy as a powerful clinical tool to detect loss of these axons as a biomarker for the presence of Lewy body disease.

  • LEWY BODY
  • NEUROPATHOLOGY
  • AUTONOMIC
  • NEURORADIOLOGY
  • SPECT

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