Chronic Fatigue Syndrome: A Presumptive Mitochondrial Disorder (CFS:M)

• Change in rate of fatigue status and other CFS symptoms [ Time Frame: 0, 3, and 6 months ] [ Designated as safety issue: No ]
  Rate of decrease in fatigue and other CFS symptoms, as measured by SF-36 and The Fatigue Assessment Instrument.
  
  

• Change in brain lactate and glutathione levels [ Time Frame: 0 and 6 months ] [ Designated as safety issue: No ]
  Patients will undergo nuclear magnetic resonance spectroscopy of the brain prior to starting therapy (baseline) and repeat it after 6 months of therapy.
  
  

Chronic fatigue syndrome (CFS), also known as myalgic encephalitis (ME), is clinically characterized as a multisystem illness exhibiting debilitating fatigue, musculoskeletal pain, disturbed sleep, and impaired memory and concentration. Its diagnosis is non-specific and symptom based, with no real biomarkers yet identified. The etiology and pathophysiology of CFS remain obscure. There is a long-standing hypothesis that individuals with CFS have normal metabolism and their fatigue is psychological, with energy being wasted through the processes of anxiety, stress, and depression. The more CFS is investigated, however, the clearer it becomes that this is incorrect, and that it is probably a metabolic dysfunction resulting in insufficient energy production. A number of studies have suggested that there may be a genetic contribution to CFS. In addition, a severe viral illness frequently predisposes the onset of CFS, while a number of pathogens have been linked to CFS (2, 3, 6). Although some patients develop CFS after an acute infection such as mononucleosis, some investigators believe it arises from the reactivation of a latent virus in the host, both resulting in a chronic low-level activation of the immune system.

As more data are acquired, we and others believe that CFS is actually a metabolic mitochondrial dysfunction resulting in insufficient energy production. Mounting evidence indicates that viral infections in genetically susceptible individuals can cause changes in mitochondrial function. Many features observed in CFS are similar to those seen in genetic mitochondrial disorders. Firstly, some muscle biopsies in patients with CFS have shown both abnormal mitochondrial degeneration and severe deletions of mitochondrial DNA genes. Mitochondrial dysfunction increases the production of free radicals and reactive oxygen species (ROS), which cause oxidative damage, believed to contribute to CFS pathogenesis. Carnitine is required for metabolic reactions including mitochondrial fatty acid oxidation. A deficiency of serum acylcarnitine has been observed in CFS patients, suggesting that there is increased utilization of carnitine in CFS, thereby decreasing energy production. In mitochondrial disorders, utilization of pyruvate is decreased, resulting in higher circulating and muscle levels of lactate, as well as decreased oxidative phosphorylation and energy production. Brain ventricular cerebrospinal lactate is elevated, and brain glutathione is decreased, in both mitochondrial disorders and CFS. In CFS patients cerebrospinal lactate is increased by approximately 300% compared to that found in generalized anxiety disorder and healthy individuals. Using brain NMR spectroscopy, the distinction between CFS and psychological disorders can be demonstrated.