title: Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An ¹¹C-(R)-PK11195 PET Study.
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. (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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan RIKEN Center for Life Science Technologies, Hyogo, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Nakatomi
authors.affiliation: 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.
authors.forename: Kei
authors.initials: K
authors.lastname: Mizuno
authors.affiliation: RIKEN Center for Life Science Technologies, Hyogo, Japan Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ishii
authors.affiliation: RIKEN Center for Life Science Technologies, Hyogo, Japan Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Wada
authors.affiliation: RIKEN Center for Life Science Technologies, Hyogo, Japan Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: RIKEN Center for Life Science Technologies, Hyogo, Japan Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shusaku
authors.initials: S
authors.lastname: Tazawa
authors.affiliation: RIKEN Center for Life Science Technologies, Hyogo, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Onoe
authors.affiliation: RIKEN Center for Life Science Technologies, Hyogo, Japan Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Sanae
authors.initials: S
authors.lastname: Fukuda
authors.affiliation: Department of Nuclear Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Joji
authors.initials: J
authors.lastname: Kawabe
authors.affiliation: RIKEN Center for Life Science Technologies, Hyogo, Japan Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: RIKEN Center for Life Science Technologies, Hyogo, Japan Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yosky
authors.initials: Y
authors.lastname: Kataoka
authors.affiliation: Department of Nuclear Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Shiomi
authors.affiliation: Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Kouzi
authors.initials: K
authors.lastname: Yamaguti
authors.affiliation: Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Inaba
authors.affiliation: 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.
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Kuratsune
authors.affiliation: RIKEN Center for Life Science Technologies, Hyogo, Japan Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan yywata@riken.jp.
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Watanabe
mesh_terms: D000328:Adult; D002250:Carbon Radioisotopes; D016207:Cytokines / Q000378:metabolism; D015673:Fatigue Syndrome, Chronic / Q000000981:diagnostic imaging* / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging / Q000378:metabolism; D007546:Isoquinolines; D008297:Male; D011877:Radionuclide Imaging
chemical_list: D002250:Carbon Radioisotopes; D016207:Cytokines; D007546:Isoquinolines; C037850:PK 11195
keywords: 11C-(R)-PK11195; chronic fatigue syndrome (CFS); myalgic encephalomyelitis (ME); neuroinflammation; positron emission tomography (PET)