Authors: Kazuhiro Yoshiuchi1,2, Jeffrey Farkas3 and Benjamin H. Natelson1
1 Department of Neurosciences, Fatigue Research Center, UMDNJ-New Jersey Medical School, Newark, NJ, USA,
2 Department of Psychosomatic Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan, and
3 Department of Radiology, Fatigue Research Center, UMDNJ-New Jersey Medical School, Newark, NJ, USA
Correspondence: Kazuhiro Yoshiuchi, Department of Psychosomatic Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan 113-8655 E-mail: firstname.lastname@example.org
Accepted for publication
Received 22 July 2005;
Accepted 6 October 2005
Key words: depression; medically unexplained illness; middle cerebral artery; psychiatric disorders; xenon computed tomography
Chronic fatigue syndrome (CFS) is a medically unexplained illness characterized by debilitating fatigue accompanied by infectious, rheumatological and neuropsychiatric symptoms. While earlier work had suggested that the severe fatigue of CFS was due to problems in the muscle, recent work does not confirm this (McCully et al., 2003). Our own findings of impaired neuropsychological function (DeLuca et al., 1995) and abnormal brain magnetic resonance scans (Lange et al., 1999) in CFS patients without comorbid psychiatric illness pointed to the brain as the target organ producing fatigue. A number of early studies using single-photon emission computed tomography (SPECT) have reported global cerebral hypoperfusion (Ichise et al., 1992; Schwartz et al., 1994). However, these studies did not divide CFS patients into those with and without co-morbid psychiatric diseases. Subsequent studies in a more homogeneous sample of CFS patients without comorbid depression reported diametrically opposite results in subcortical sites; one group found decreases in brain stem perfusion (Costa et al., 1995) while another group found increased perfusion in the thalamus. In contrast, at least three studies - one in carefully matched monozygotic twins discordant for CFS - found no differences in cerebral blood flow (CBF) between patients and controls (Peterson et al., 1994; Fischler et al., 1996; Lewis et al., 2001). Therefore, sample heterogeneity does not appear to be an adequate explanation for these discrepancies.
An alternative explanation is a methodological issue. SPECT scanning provides information about the whole brain blood flow relative to some other site - usually the cerebellum. If some CFS patients had reduced blood flow to cerebellum, this occurrence might greatly confound the results.
Therefore, the aim of this study was to test the hypothesis that patients with CFS have reduced absolute CBF using Xenon computed tomography (CT), a method that provides absolute measures of CBF. In addition, a stratification strategy was used as recommended by the Centers for Disease Control to reduce heterogeneity in the patient sample by dividing CFS patients into those with and without comorbid Axis I psychiatric disorders. Our previous use of that strategy had produced a subset of patients with neuropsychological dysfunction and increased numbers of brain magnetic resonance imaging (MRI) abnormalities relative to patients with comorbid psychopathology (Natelson, 2001).
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