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J Nucl Med. 2014 Jun;55(6):945-50. doi: 10.2967/jnumed.113.131045. Epub 2014 Mar 24.

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

Author information

  • 1Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan RIKEN Center for Life Science Technologies, Hyogo, Japan.
  • 2RIKEN 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.
  • 3RIKEN Center for Life Science Technologies, Hyogo, Japan Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan.
  • 4RIKEN Center for Life Science Technologies, Hyogo, Japan.
  • 5Department of Nuclear Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
  • 6Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan.
  • 7Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
  • 8Department 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.
  • 9RIKEN Center for Life Science Technologies, Hyogo, Japan Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan yywata@riken.jp.

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.

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.

KEYWORDS:

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

PMID:
24665088
DOI:
10.2967/jnumed.113.131045
[PubMed - indexed for MEDLINE]
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