Increased ventricular lactate in chronic fatigue syndrome

Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology

Dikoma C. Shungu1,*, Nora Weiduschat1, James W. Murrough2, Xiangling Mao1, Sarah Pillemer2, Jonathan P. Dyke1, Marvin S. Medow3, Benjamin H. Natelson4, Julian M. Stewart3, Sanjay J. Mathew2,5Article first published online: 27 JAN 2012

DOI: 10.1002/nbm.2772

Copyright 2012 John Wiley & Sons, Ltd.

Pathophysiological model of chronic fatigue syndrome (CFS) which attempts to explain the consistent observation of cross-sectional elevations of ventricular lactate in the disorder. Highlighted are the experimentally measurable items, with the red arrows showing the model-predicted outcomes. This series of neuroimaging studies aimed to validate this model by measuring each key item and comparing the results with the model-predicted outcomes.

Chronic fatigue syndrome (CFS) is a complex illness, which is often misdiagnosed as a psychiatric illness. In two previous reports, using 1H MRSI, we found significantly higher levels of ventricular cerebrospinal fluid (CSF) lactate in patients with CFS relative to those with generalized anxiety disorder and healthy volunteers (HV), but not relative to those with major depressive disorder (MDD).

In this third independent cross-sectional neuroimaging study, we investigated a pathophysiological model which postulated that elevations of CSF lactate in patients with CFS might be caused by increased oxidative stress, cerebral hypoperfusion and/or secondary mitochondrial dysfunction.

Fifteen patients with CFS, 15 with MDD and 13 HVs were studied using the following modalities: (i) 1H MRSI to measure CSF lactate; (ii) single-voxel 1H MRS to measure levels of cortical glutathione (GSH) as a marker of antioxidant capacity; (iii) arterial spin labeling (ASL) MRI to measure regional cerebral blood flow (rCBF); and (iv) 31P MRSI to measure brain high-energy phosphates as objective indices of mitochondrial dysfunction.
We found elevated ventricular lactate and decreased GSH (glutathion) in patients with CFS and MDD relative to HVs. GSH did not differ significantly between the two patient groups. In addition, we found lower rCBF in the left anterior cingulate cortex and the right lingual gyrus in patients with CFS relative to HVs, but rCBF did not differ between those with CFS and MDD.

We found no differences between the three groups in terms of any high-energy phosphate metabolites. In exploratory correlation analyses, we found that levels of ventricular lactate and cortical GSH were inversely correlated, and significantly associated with several key indices of physical health and disability. Collectively, the results of this third independent study support a pathophysiological model of CFS in which increased oxidative stress may play a key role in CFS etiopathophysiology.

Copyright 2012 John Wiley & Sons, Ltd.


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