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Research ArticleClinical Investigation

Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An 11C-(R)-PK11195 PET Study

Yasuhito Nakatomi, Kei Mizuno, Akira Ishii, Yasuhiro Wada, Masaaki Tanaka, Shusaku Tazawa, Kayo Onoe, Sanae Fukuda, Joji Kawabe, Kazuhiro Takahashi, Yosky Kataoka, Susumu Shiomi, Kouzi Yamaguti, Masaaki Inaba, Hirohiko Kuratsune and Yasuyoshi Watanabe
Journal of Nuclear Medicine March 2014, jnumed.113.131045; DOI: https://doi.org/10.2967/jnumed.113.131045
Yasuhito Nakatomi
1Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
2RIKEN Center for Life Science Technologies, Hyogo, Japan
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Kei Mizuno
2RIKEN Center for Life Science Technologies, Hyogo, Japan
3Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan
4Department of Medical Science on Fatigue, Osaka City University Graduate School of Medicine, Osaka, Japan
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Akira Ishii
2RIKEN Center for Life Science Technologies, Hyogo, Japan
3Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan
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Yasuhiro Wada
2RIKEN Center for Life Science Technologies, Hyogo, Japan
3Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan
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Masaaki Tanaka
2RIKEN Center for Life Science Technologies, Hyogo, Japan
3Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan
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Shusaku Tazawa
2RIKEN Center for Life Science Technologies, Hyogo, Japan
3Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan
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Kayo Onoe
2RIKEN Center for Life Science Technologies, Hyogo, Japan
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Sanae Fukuda
2RIKEN Center for Life Science Technologies, Hyogo, Japan
3Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan
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Joji Kawabe
5Department of Nuclear Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
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Kazuhiro Takahashi
2RIKEN Center for Life Science Technologies, Hyogo, Japan
3Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan
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Yosky Kataoka
2RIKEN Center for Life Science Technologies, Hyogo, Japan
3Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan
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Susumu Shiomi
5Department of Nuclear Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
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Kouzi Yamaguti
3Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan
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Masaaki Inaba
1Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
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Hirohiko Kuratsune
3Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan
6Department of Health Science, Kansai University of Welfare Sciences, Osaka, Japan; and
7Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan
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Yasuyoshi Watanabe
2RIKEN Center for Life Science Technologies, Hyogo, Japan
3Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan
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Abstract

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disease characterized by chronic, profound, disabling, and unexplained fatigue. Although it is hypothesized that brain inflammation is involved in the pathophysiology of CFS/ME, there is no direct evidence of neuroinflammation in patients with CFS/ME. Activation of microglia or astrocytes is related to neuroinflammation. 11C-(R)-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxamide (11C-(R)-PK11195) is a ligand of PET for a translocator protein that is expressed by activated microglia or astrocytes. We used 11C-(R)-PK11195 and PET to investigate the existence of neuroinflammation in CFS/ME patients. Methods: Nine CFS/ME patients and 10 healthy controls underwent 11C-(R)-PK11195 PET and completed questionnaires about fatigue, fatigue sensation, cognitive impairments, pain, and depression. To measure the density of translocator protein, nondisplaceable binding potential (BPND) values were determined using linear graphical analysis with the cerebellum as a reference region. Results: The BPND values of 11C-(R)-PK11195 in the cingulate cortex, hippocampus, amygdala, thalamus, midbrain, and pons were 45%–199% higher in CFS/ME patients than in healthy controls. In CFS/ME patients, the BPND values of 11C-(R)-PK11195 in the amygdala, thalamus, and midbrain positively correlated with cognitive impairment score, the BPND values in the cingulate cortex and thalamus positively correlated with pain score, and the BPND value in the hippocampus positively correlated with depression score. Conclusion: Neuroinflammation is present in widespread brain areas in CFS/ME patients and was associated with the severity of neuropsychologic symptoms. Evaluation of neuroinflammation in CFS/ME patients may be essential for understanding the core pathophysiology and for developing objective diagnostic criteria and effective medical treatments.

  • neuroinflammation
  • chronic fatigue syndrome (CFS)
  • myalgic encephalomyelitis (ME)
  • 11C-(R)-PK11195
  • positron emission tomography (PET)

Footnotes

  • Published online ▪▪▪▪▪▪▪▪▪▪▪▪.

  • © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
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Journal of Nuclear Medicine: 66 (5)
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Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An 11C-(R)-PK11195 PET Study
Yasuhito Nakatomi, Kei Mizuno, Akira Ishii, Yasuhiro Wada, Masaaki Tanaka, Shusaku Tazawa, Kayo Onoe, Sanae Fukuda, Joji Kawabe, Kazuhiro Takahashi, Yosky Kataoka, Susumu Shiomi, Kouzi Yamaguti, Masaaki Inaba, Hirohiko Kuratsune, Yasuyoshi Watanabe
Journal of Nuclear Medicine Mar 2014, jnumed.113.131045; DOI: 10.2967/jnumed.113.131045

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Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An 11C-(R)-PK11195 PET Study
Yasuhito Nakatomi, Kei Mizuno, Akira Ishii, Yasuhiro Wada, Masaaki Tanaka, Shusaku Tazawa, Kayo Onoe, Sanae Fukuda, Joji Kawabe, Kazuhiro Takahashi, Yosky Kataoka, Susumu Shiomi, Kouzi Yamaguti, Masaaki Inaba, Hirohiko Kuratsune, Yasuyoshi Watanabe
Journal of Nuclear Medicine Mar 2014, jnumed.113.131045; DOI: 10.2967/jnumed.113.131045
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Keywords

  • neuroinflammation
  • chronic fatigue syndrome (CFS)
  • myalgic encephalomyelitis (ME)
  • 11C-(R)-PK11195
  • positron emission tomography (PET)
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