Yasuhito Nakatomi1, Kei Mizuno2, Akira Ishii3, Yasuhiro Wada3, Masaaki Tanaka3, Shusaku Tazawa3, Kayo Onoe4, Sanae Fukuda3, Joji Kawabe5, Kazuhiro Takahashi3, Yosky Kataoka3, Susumu Shiomi5, Kouzi Yamaguti6, Masaaki Inaba7, Hirohiko Kuratsune8, Yasuyoshi Watanabe9. 1. Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan RIKEN Center for Life Science Technologies, Hyogo, Japan. 2. RIKEN Center for Life Science Technologies, Hyogo, Japan Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan Department of Medical Science on Fatigue, Osaka City University Graduate School of Medicine, Osaka, Japan. 3. RIKEN Center for Life Science Technologies, Hyogo, Japan Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan. 4. RIKEN Center for Life Science Technologies, Hyogo, Japan. 5. Department of Nuclear Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan. 6. Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan. 7. Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan. 8. Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan Department of Health Science, Kansai University of Welfare Sciences, Osaka, Japan; and Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan. 9. RIKEN Center for Life Science Technologies, Hyogo, Japan Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan yywata@riken.jp.
Abstract
UNLABELLED: 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. (11)C-(R)-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxamide ((11)C-(R)-PK11195) is a ligand of PET for a translocator protein that is expressed by activated microglia or astrocytes. We used (11)C-(R)-PK11195 and PET to investigate the existence of neuroinflammation in CFS/ME patients. METHODS: Nine CFS/ME patients and 10 healthy controls underwent (11)C-(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 (BP(ND)) values were determined using linear graphical analysis with the cerebellum as a reference region. RESULTS: The BP(ND) values of (11)C-(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 BP(ND) values of (11)C-(R)-PK11195 in the amygdala, thalamus, and midbrain positively correlated with cognitive impairment score, the BP(ND) values in the cingulate cortex and thalamus positively correlated with pain score, and the BP(ND) 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.
UNLABELLED: 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. (11)C-(R)-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxamide ((11)C-(R)-PK11195) is a ligand of PET for a translocator protein that is expressed by activated microglia or astrocytes. We used (11)C-(R)-PK11195 and PET to investigate the existence of neuroinflammation in CFS/ME patients. METHODS: Nine CFS/ME patients and 10 healthy controls underwent (11)C-(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 (BP(ND)) values were determined using linear graphical analysis with the cerebellum as a reference region. RESULTS: The BP(ND) values of (11)C-(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 BP(ND) values of (11)C-(R)-PK11195 in the amygdala, thalamus, and midbrain positively correlated with cognitive impairment score, the BP(ND) values in the cingulate cortex and thalamus positively correlated with pain score, and the BP(ND) 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.
Authors: L V Clark; M Buckland; G Murphy; N Taylor; V Vleck; C Mein; E Wozniak; M Smuk; P D White Journal: Clin Exp Immunol Date: 2017-10-11 Impact factor: 4.330
Authors: S Sahbai; P Kauv; M Abrivard; P Blanc-Durand; M Aoun-Sebati; B Emsen; A Luciani; J Hodel; F-J Authier; E Itti Journal: Eur J Nucl Med Mol Imaging Date: 2018-12-14 Impact factor: 9.236