Quantitative correlation between cardiac MIBG uptake and remaining axons in the cardiac sympathetic nerve in Lewy body disease.
OBJECTIVE
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 (123)I-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 (123)I-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 (123)I-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.
Department of Neurology, Kanto Central Hospital, Tokyo, Japan.
Makoto
M
Takahashi
Division of Pathology, Kanto Central Hospital, Tokyo, Japan.
Masako
M
Ikemura
Division of Pathology, Kanto Central Hospital, Tokyo, Japan.
Teruaki
T
Oka
Laboratory of Structural Neuropathology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Toshiki
T
Uchihara
Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Koichi
K
Wakabayashi
Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.
Akiyoshi
A
Kakita
Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.
Hitoshi
H
Takahashi
Institute for Medical Science of Aging, Aichi Medical University, Nagakute, Japan.
Mari
M
Yoshida
Department of Neurology, Nakano General Hospital, Tokyo, Japan.
Shuta
S
Toru
Department of Neurology, Nakano General Hospital, Tokyo, Japan.
Takayoshi
T
Kobayashi
Department of Neurology, Kanto Central Hospital, Tokyo, Japan.
Satoshi
S
Orimo
D000368:Aged; D000369:Aged, 80 and over; D001369:Axons / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006801:Humans; D007382:Intermediate Filaments / Q000378:metabolism; D020961:Lewy Body Disease / Q000175:diagnosis* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D055414:Myocardial Perfusion Imaging; D013564:Sympathetic Nervous System / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D015415:Biomarkers; D014446:Tyrosine 3-Monooxygenase
AUTONOMIC; LEWY BODY; NEUROPATHOLOGY; NEURORADIOLOGY; SPECT