Brain Hypoperfusion

From: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896084/">Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology</a>

In this study, we found limited regions of hypoperfusion in patients with CFS relative to HVs, a finding that is in agreement with most (<a id="tag_350125361" class="bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896084/#R8">8</a>–<a id="tag_350125382" class=" bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896084/#R11">11</a>,<a id="tag_403317083" class=" bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896084/#R39">39</a>), but not all (<a id="tag_350125393" class=" bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896084/#R40">40</a>,<a id="tag_350125330" class=" bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896084/#R41">41</a>), previous measurements of rCBF using single-photon emission computed tomography (SPECT) (<a id="tag_350125419" class="bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896084/#R8">8</a>,<a id="tag_350125354" class=" bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896084/#R9">9</a>,<a id="tag_403317081" class=" bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896084/#R39">39</a>–<a id="tag_350125355" class=" bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896084/#R41">41</a>), Xe computed tomography (<a id="tag_350125423" class=" bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896084/#R10">10</a>) or ASL (<a id="tag_350125424" class=" bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896084/#R11">11</a>). In nearly all studies that found CBF deficits in patients with CFS, multiple regions were reported to be involved (<a id="tag_350125376" class="bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896084/#R8">8</a>,<a id="tag_350125407" class=" bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896084/#R9">9</a>,<a id="tag_350125323" class=" bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896084/#R11">11</a>,<a id="tag_403317070" class=" bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896084/#R39">39</a>), with some of the regions of hypoperfusion being as small as or less than 1 cm (<a id="tag_350125370" class=" bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896084/#R33">33</a>).

It is unclear whether the degree of hypoperfusion found in patients with CFS by these multiple techniques is sufficient to trigger increased glycolytic activity that could account for our observed elevations of ventricular lactate. However, at least three threshold levels of cell hypoxia have been described (<a id="tag_350125360" class=" bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896084/#R42">42</a>), one of which could plausibly trigger increased glycolytic rates in patients with CFS: (i) decreased oxygen tension, but the cell's ATP production remains able to meet energy demand through changes in phosphorylation state and increased glycolysis; (ii) an oxygenation level at which steady-state ATP levels can be maintained only by increased anaerobic glycolysis through the very inefficient Embden–Meyerhof pathway, which is not sustainable in a high-energy-consuming organ, such as the brain, leading to rapid ATP depletion; and (iii) an oxygenation level at which anaerobic glycolysis is no longer able to generate sufficient ATP to maintain cell function. As we did not find deficits in ATP in this study (see Results section), and the levels of ventricular lactate measured in patients with CFS are relatively small relative to those reported previously in fully symptomatic patients with primary mitochondrial disorders (<a id="tag_350125331" class=" bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896084/#R43">43</a>) or cerebral infarction (<a id="tag_350125343" class=" bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896084/#R44">44</a>), we postulate that the observed ventricular lactate elevations may be triggered by a decrease in oxygenation level corresponding to the first aforementioned threshold level (i.e. mild to moderate hypoxia), which may result from CBF decreases found in this and previous studies (<a id="tag_350125383" class="bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896084/#R8">8</a>–<a id="tag_350125418" class=" bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896084/#R11">11</a>,<a id="tag_403317080" class=" bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896084/#R39">39</a>). However, direct evidence of altered tissue oxygenation in patients with CFS is necessary to establish a definite mechanistic link between rCBF decreases and the observed lactate elevations.