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Research:

Patients with chronic fatigue syndrome have reduced absolute cortical blood flow

Journal: Clinical Physiology Functional Imaging, Vol. 26, #2, pp 83-86, March 2006

Authors: Kazuhiro Yoshiuchi1,2, Jeffrey Farkas3 and Benjamin H. Natelson1

Affiliations:
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: kyoshiuc-tky@umin.ac.jp

Accepted for publication
Received 22 July 2005;
Accepted 6 October 2005

Summary
Prior studies on brain blood flow in chronic fatigue syndrome (CFS) did not find consistent results. This may be because they used single-photon emission computed tomography to measure brain blood flow, which could not measure absolute blood flow. Therefore, the aim of this study was to test the hypothesis that patients with CFS have reduced absolute cerebral blood flow. Xenon-computed tomography blood flow studies were done on 25 CFS patients and seven healthy controls. Analyses were done after stratifying the CFS patients based on the presence or absence of a current psychiatric disorder. Flow was diminished in both groups as follows: patients with no current psychiatric disorders had reduced cortical blood flow in the distribution of both right and left middle cerebral arteries (P<0.05 for both) while those with current psychiatric disorders had reduced blood flow only in the left middle cerebral artery territory (P<0.05). These data indicate that patients with CFS have reduced absolute cortical blood flow in rather broad areas when compared with data from healthy controls and that those devoid of psychopathology had the most reductions in cortical flow. These data support, in part, our earlier findings that patients devoid of psychopathology are the group most at risk of having some of the symptoms of CFS due to brain dysfunction.

Key words: depression; medically unexplained illness; middle cerebral artery; psychiatric disorders; xenon computed tomography

Introduction
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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