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Is Generalized and Segmental Dystonia Accompanied by Impairments in the Dopaminergic System?

Background: The pathogenesis of dystonia is remarkably diverse. Some types of dystonia, such as DYT5 (DYT-GCH1) and tardive dystonia, are related to dysfunction of the dopaminergic system. Furthermore, on pathological examination, cell loss in the substantia nigra (SN) of patients with dystonia has...

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Autores principales: Ikezawa, Jun, Yokochi, Fusako, Okiyama, Ryoichi, Kumada, Satoko, Tojima, Maya, Kamiyama, Tsutomu, Hanakawa, Takashi, Matsuda, Hiroshi, Tanaka, Fumiaki, Nakata, Yasuhiro, Isozaki, Eiji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8638468/
https://www.ncbi.nlm.nih.gov/pubmed/34867735
http://dx.doi.org/10.3389/fneur.2021.751434
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author Ikezawa, Jun
Yokochi, Fusako
Okiyama, Ryoichi
Kumada, Satoko
Tojima, Maya
Kamiyama, Tsutomu
Hanakawa, Takashi
Matsuda, Hiroshi
Tanaka, Fumiaki
Nakata, Yasuhiro
Isozaki, Eiji
author_facet Ikezawa, Jun
Yokochi, Fusako
Okiyama, Ryoichi
Kumada, Satoko
Tojima, Maya
Kamiyama, Tsutomu
Hanakawa, Takashi
Matsuda, Hiroshi
Tanaka, Fumiaki
Nakata, Yasuhiro
Isozaki, Eiji
author_sort Ikezawa, Jun
collection PubMed
description Background: The pathogenesis of dystonia is remarkably diverse. Some types of dystonia, such as DYT5 (DYT-GCH1) and tardive dystonia, are related to dysfunction of the dopaminergic system. Furthermore, on pathological examination, cell loss in the substantia nigra (SN) of patients with dystonia has been reported, suggesting that impaired dopamine production may be involved in DYT5 and in other types of dystonia. Objectives: To investigate functional dopaminergic impairments, we compared patients with dystonia and those with Parkinson's disease (PD) with normal controls using neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and dopamine transporter single photon emission computed tomography (DAT SPECT). Methods: A total of 18, 18, and 27 patients with generalized or segmental dystonia, patients with PD, and healthy controls, respectively, were examined using NM-MRI. The mean area corresponding to NM in the SN (NM-SN) was blindly quantified. DAT SPECT was performed on 17 and eight patients with dystonia and PD, respectively. The imaging data of DAT SPECT were harmonized with the Japanese database using striatum phantom calibration. These imaging data were compared between patients with dystonia or PD and controls from the Japanese database in 256 healthy volunteers using the calibrated specific binding ratio (cSBR). The symptoms of dystonia were evaluated using the Fahn–Marsden Dystonia Rating Scale (FMDRS), and the correlation between the results of imaging data and FMDRS was examined. Results: The mean areas corresponding to NM in the SN (NM-SN) were 31 ± 4.2, 28 ± 3.8, and 43 ± 3.8 pixels in patients with dystonia, PD, and in healthy controls, respectively. The mean cSBRs were 5 ± 0.2, 2.8 ± 0.2, 9.2 (predictive) in patients with dystonia, PD, and in healthy controls, respectively. The NM-SN area (r = −0.49, p < 0.05) and the cSBR (r = −0.54, p < 0.05) were inversely correlated with the FMDRS. There was no significant difference between the dystonia and PD groups regarding NM-SN (p = 0.28). In contrast, the cSBR was lower in patients with PD than in those with dystonia (p < 0.5 × 10(−6)). Conclusions: Impairments of the dopaminergic system may be involved in developing generalized and segmental dystonia. SN abnormalities in patients with dystonia were supposed to be different from degeneration in PD.
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spelling pubmed-86384682021-12-03 Is Generalized and Segmental Dystonia Accompanied by Impairments in the Dopaminergic System? Ikezawa, Jun Yokochi, Fusako Okiyama, Ryoichi Kumada, Satoko Tojima, Maya Kamiyama, Tsutomu Hanakawa, Takashi Matsuda, Hiroshi Tanaka, Fumiaki Nakata, Yasuhiro Isozaki, Eiji Front Neurol Neurology Background: The pathogenesis of dystonia is remarkably diverse. Some types of dystonia, such as DYT5 (DYT-GCH1) and tardive dystonia, are related to dysfunction of the dopaminergic system. Furthermore, on pathological examination, cell loss in the substantia nigra (SN) of patients with dystonia has been reported, suggesting that impaired dopamine production may be involved in DYT5 and in other types of dystonia. Objectives: To investigate functional dopaminergic impairments, we compared patients with dystonia and those with Parkinson's disease (PD) with normal controls using neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and dopamine transporter single photon emission computed tomography (DAT SPECT). Methods: A total of 18, 18, and 27 patients with generalized or segmental dystonia, patients with PD, and healthy controls, respectively, were examined using NM-MRI. The mean area corresponding to NM in the SN (NM-SN) was blindly quantified. DAT SPECT was performed on 17 and eight patients with dystonia and PD, respectively. The imaging data of DAT SPECT were harmonized with the Japanese database using striatum phantom calibration. These imaging data were compared between patients with dystonia or PD and controls from the Japanese database in 256 healthy volunteers using the calibrated specific binding ratio (cSBR). The symptoms of dystonia were evaluated using the Fahn–Marsden Dystonia Rating Scale (FMDRS), and the correlation between the results of imaging data and FMDRS was examined. Results: The mean areas corresponding to NM in the SN (NM-SN) were 31 ± 4.2, 28 ± 3.8, and 43 ± 3.8 pixels in patients with dystonia, PD, and in healthy controls, respectively. The mean cSBRs were 5 ± 0.2, 2.8 ± 0.2, 9.2 (predictive) in patients with dystonia, PD, and in healthy controls, respectively. The NM-SN area (r = −0.49, p < 0.05) and the cSBR (r = −0.54, p < 0.05) were inversely correlated with the FMDRS. There was no significant difference between the dystonia and PD groups regarding NM-SN (p = 0.28). In contrast, the cSBR was lower in patients with PD than in those with dystonia (p < 0.5 × 10(−6)). Conclusions: Impairments of the dopaminergic system may be involved in developing generalized and segmental dystonia. SN abnormalities in patients with dystonia were supposed to be different from degeneration in PD. Frontiers Media S.A. 2021-11-18 /pmc/articles/PMC8638468/ /pubmed/34867735 http://dx.doi.org/10.3389/fneur.2021.751434 Text en Copyright © 2021 Ikezawa, Yokochi, Okiyama, Kumada, Tojima, Kamiyama, Hanakawa, Matsuda, Tanaka, Nakata and Isozaki. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Ikezawa, Jun
Yokochi, Fusako
Okiyama, Ryoichi
Kumada, Satoko
Tojima, Maya
Kamiyama, Tsutomu
Hanakawa, Takashi
Matsuda, Hiroshi
Tanaka, Fumiaki
Nakata, Yasuhiro
Isozaki, Eiji
Is Generalized and Segmental Dystonia Accompanied by Impairments in the Dopaminergic System?
title Is Generalized and Segmental Dystonia Accompanied by Impairments in the Dopaminergic System?
title_full Is Generalized and Segmental Dystonia Accompanied by Impairments in the Dopaminergic System?
title_fullStr Is Generalized and Segmental Dystonia Accompanied by Impairments in the Dopaminergic System?
title_full_unstemmed Is Generalized and Segmental Dystonia Accompanied by Impairments in the Dopaminergic System?
title_short Is Generalized and Segmental Dystonia Accompanied by Impairments in the Dopaminergic System?
title_sort is generalized and segmental dystonia accompanied by impairments in the dopaminergic system?
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8638468/
https://www.ncbi.nlm.nih.gov/pubmed/34867735
http://dx.doi.org/10.3389/fneur.2021.751434
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