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Cornell Studies Point to Oxidative Stress as Major Factor in ME/CFS Symptoms

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Article:
Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology
– Source: NMR in Biomedicine, Jan 27, 2012

Dikoma Shungu, et al.

[Note: This is a continuation of a Cornell research team’s work to measure anomalies in ME/CFS. Previously they found elevated ventricular lactate levels in ME/CFS cerebrospinal fluid by comparison with healthy controls and patients with anxiety disorder. Another study found that cerebrospinal lactate is also elevated in patients with major depressive disorder. The higher the cerebrospinal lactate levels in ME/CFS patients, the more severe their mental fatigue. The current report points to a possible connection between this ventricular lactate elevation and oxidative stress. Oxidative stress is damage to cells caused by an excess of free radicals. In a process similar to rusting of metal, the rogue free radicals damage DNA and inhibit cellular metabolism & energy generation. (Antioxidants work to neutralize excess free radicals.)]

Abstract:
Chronic fatigue syndrome (CFS) is a complex illness, which is often misdiagnosed as a psychiatric illness. In two previous reports, using (1) H 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 [reduced blood flow] and/or secondary mitochondrial dysfunction.

Fifteen patients with CFS, 15 with MDD and 13 HVs were studied using the following modalities:

• (1) H MRSI to measure CSF lactate;

• Single-voxel (1) H MRS to measure levels of cortical glutathione (GSH) as a marker of antioxidant capacity;

• Arterial spin labeling (ASL) MRI to measure regional cerebral blood flow (rCBF); and

• (31) P MRSI to measure brain high-energy phosphates as objective indices of mitochondrial dysfunction.

We found elevated ventricular lactate and decreased cortical glutathione in patients with CFS and major depressive disorder relative to healthy volunteers.

Cortical glutathione did not differ significantly between the two patient groups [CFS and MDD].

In addition, we found lower regional cerebral blood flow in the left anterior cingulate cortex and the right lingual gyrus in patients with CFS relative to healthy volunteers,

But regional cerebral blood flow did not differ between those with CFS and major depressive disorder.

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 glutathione were inversely correlated [more ventricular lactate, less GSH], 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.

Source:
NMR in Biomedicine, Jan 27, 2012. PMID:22281935, by  Shungu DC, Weiduschat N, Murrough JW, Mao X, Pillemer S, Dyke JP, Medow MS, Natelson BH, Stewart JM, Mathew SJ. Department of Radiology, Weill Medical College of Cornell University, New York, NY, USA. [Email: dcs7001@med.cornell.edu]

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