Journal of IiME Volume 5 Issue 1 (May 2011) The Involvement of the PACE Trial Principal Investigators and the Director of the Clinical Trials Unit with the Department for Work and Pensions continued stimulus, which in turn could lead to hypocortisolism seen in ME/CFS patients, and that seizure activity may spread to adjacent structures of the limbic-hypothalamic-pituitary axis in the brain, which might be responsible for the varied symptoms that occur in ME/CFS patients. Jason et al cite impressive supporting evidence, for example, Broderick, Fletcher and Klimas et al “applied network analysis to cytokines in patients with ME/CFS and healthy controls, and outcomes were consistent with a latent viral infection (ie. attenuated Th1 and Th17 immune responses, an established Th2 inflammatory milieu, and diminished NK cell responsiveness)….Chronic cortisol deficiency can cause over-production of the proinflammatory cytokine interleukin-6 (IL-6), which has been associated with symptoms of ME/CFS. Lower cortisol, as well as an overactive sympathetic nervous system, could be responsible for the ejection fraction decreases (fraction of blood pumped out of the ventricles per heartbeat) and lower cardiac output among patients with ME/CFS….Because of the Th2 shift, the body would not have an effective defence against viral or intracellular infections….”. “Baraniuk et al suggested that patients with ME/CFS had unusual proteins in the cerebrospinal fluid, and the aggregation of these abnormal proteins…could cause small amounts of bleeding in the brain (by) causing small punctures in the blood vessels and then small amounts of blood leak into the brain. Other proteins suggest a proteaseantiprotease imbalance, increased free radical production, vasoconstriction of the blood vessels, inflammation, and altered rates of cell suicide. Baraniuk et al suggest that inflammation, haemorrhagic elements, increased cell death, and free radical production could be by-products of damage (by these) abnormally folded proteins impeding blood flow and ultimately puncturing blood vessels in the brain”. Invest in ME (Charity Nr. 1114035) “Biswal, Kunwar and Natelson found significant cerebral blood flow reductions in nearly every region of the brain assessed….Neary et al tested whether patients with ME/CFS have reduced oxygen delivery to the brain during and after exercise challenge. They found that in addition to significant exercise intolerance, patients in comparison to controls (have) reduced prefrontal oxygenation, suggesting altered cerebral oxygenation and blood volume in the brain….Neurotropic viral infections could be responsible for the appearance of lesions in the brain and the presence of focal epileptiform seizure activity”. Referring to the work of Light et al, Jason notes that “Light et al maintain that exercise could send a continuous signal of muscle sensory fatigue to the central nervous system causing dysregulation of sympathetic nervous system reflexes….About 90% of the ME/CFS patients could be distinguished from control subjects using just 4 of the genes measured…The researchers concluded that ME/CFS patients might have enhanced sensory signal for fatigue that is increased after exercise. These finding all indicate persistent changes in cell membrane function”. Referring to his earlier (2009) work, Jason notes that it: “suggests that being over-extended and going beyond energy reserves can be an impediment to improving functionality and fatigue levels” and it concludes that “specific environmental cues” may trigger ME/CFS. He is clear: “We need studies based on systems biology that explain the illness, in combination with more details about the environmental contributors to the illness”. None of these proven pathologies can be ascribed to deconditioning or to abnormal illness beliefs that are reversible with cognitive restructuring and aerobic exercise. Just as Peter Dewis of UNUMprovident sees a challenge in ensuring that people are directed towards the Wessely School‟s behavioural approach, a far greater challenge faces the Continued page 41 www.investinme.org Page 40/58

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