Cerebral blood flow is reduced in chronic fatigue syndrome as assessed by arterial spin labeling

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Abstract

Background

Chronic fatigue syndrome is diagnosed by a set of clinical criteria and therefore is probably heterogeneous. Earlier reports tested the hypothesis that the syndrome had a neurological substrate by doing studies of cerebral blood flow (CBF) but with discrepant results. One possible reason for the discrepancy was that relative CBF was assessed. We found reduced CBF in an earlier study of absolute CBF using xenon-CT. The purpose of this study was to use a second method of assessing CBF and to look within the study group for heterogeneity of responses.

Method

Eleven CFS patients and 10 age matched healthy controls underwent neuroimaging using arterial spin labeling to determine their regional and global absolute CBF. A template was constructed based on the control data, and individual patient montages were compared on a case by case basis to determine if differences in regions of interest occurred.

Results

The patients as a group had significantly lower global CBF than the controls. The reduction in CBF occurred across nearly every region assessed. Nine of the 11 patients showed these reductions compared to the average control data, while two patients showed actual increases relative to the controls.

Conclusion

The data extend our earlier observation that CFS patients as a group have broad decreases in CBF compared to healthy controls. However, as expected, the effect was not homogeneous in that 2 of the 11 patients studied showed actual increases in CBF relative to controls.

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 muscle, more recent work does not confirm this [1]. Our own findings of impaired neuropsychological function [2] and abnormal brain MR scans [3] in CFS patients without comorbid psychiatric illness pointed to the brain as the target organ producing fatigue. One mechanism for this might be globally reduced cerebral blood flow (CBF). A number of early studies using single-photon emission computerized tomography (SPECT) have reported global cerebral hypoperfusion [4], [5]. However, three studies – one in carefully matched monozygotic twins discordant for CFS – found no differences in cerebral blood flow (CBF) between patients and controls [6], [7], [8].

One explanation for this apparent discrepancy is a methodological issue. SPECT scanning provides information about 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. Because of this, we turned to a method that provided information on absolute CBF — xenon-CT. In that study [9], we found a statistically significant group effect: CBF was significantly lower in the patients than in matched healthy controls.

A second method that produces data uses arterial spin labeling (ASL), a method of functional neuroimaging using magnetic resonance (MR) methodology. One major advantage of this technique compared to xenon-CT is that this form of functional neuroimaging allows the collection of data without the need for patients to be exposed to radiation. Therefore, we decided to determine if we could replicate our earlier finding of reduced CBF using this alternative method and then to extend that work to determine if individual differences in CBF existed among CFS patients.

Section snippets

Protocol

Eleven patients who fulfilled the 1994 case definition [10] for CFS and ten age matched (± 5 years) healthy volunteers were scanned for this study after obtaining signed informed consent approved by the Institutional Review Board of the New Jersey Medical School. Subjects were positioned supine on the MRI bed of 3 T research Siemens Allegra scanner with head in a midline location in the coil and were instructed not to move their head during the session.

Images were acquired using a 3-axis

Results

Motion was not found to be significant in any of the runs for each of the subjects, and no significant difference in motion was observed between the two groups.

Spatial maps of arterial spin labeled images were obtained for each of the subjects (both CFS and matched controls). A number of anatomical regions had significant differences between the two groups. The CFS group had a significant reduction compared with matched controls on whole brain blood flow as well as on the following areas of

Discussion

This paper confirms and extends our earlier observation that patients with chronic fatigue syndrome as a group have diminished cerebral blood flow relative to matched controls — even when the data are corrected for volume of brain tissue. Importantly, both this paper and our earlier one using xenon-CT [9] used a method that assessed absolute CBF rather than the relative measure used in earlier studies with other methodologies. The reduction in CBF was quite diffuse sparing only the right

Acknowledgement

The work reported here was supported in part by NIH Grants AI-32247 and AI-54478 to BHN.

References (13)

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