Multimodal and simultaneous assessments of brain and spinal fluid abnormalities in chronic fatigue syndrome and the effects of psychiatric comorbidity

Abstract

The purpose of this study was to investigate whether CFS patients without comorbid psychiatric diagnoses differ from CFS patients with comorbid psychiatric diagnoses and healthy control subjects in neuropsychological performance, the proportion with elevated spinal fluid protein or white cell counts, cerebral blood flow (CBF), brain ventricular lactate and cortical glutathione (GSH). The results of the study did not show any differences in any of the outcome measures between CFS patients with and without psychiatric comorbidity, thus indicating that psychiatric status may not be an exacerbating factor in CFS. Importantly, significant differences were found between the pooled samples of CFS compared to controls. These included lower GSH and CBF and higher ventricular lactate and rates of spinal fluid abnormalities in CFS patients compared to healthy controls. Thirteen of 26 patients had abnormal values on two or more of these 4 brain-related variables. These findings, which replicate the results of several of our prior studies, support the presence of a number of neurobiological and spinal fluid abnormalities in CFS. These results will lead to further investigation into objective biomarkers of the disorder to advance the understanding of CFS.

Neuroimaging characteristics of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review

“…Using MR spectroscopy, lower N-acetylaspartate concentration in the hippocampus [ 50 ], lower cortical glutathione levels [ 51 , 52 ], higher choline concentration in the basal ganglia [ 53 ], higher lactate concentrations in the lateral ventricles (from a same group) [ 51 , 52 , 54 – 56 ], higher choline to creatine ratio in the occipital cortex [ 57 ] have been reported in ME/CFS. No differences in -aminobutyric acid nor glutamate + glutamine either in the occipital cortex or anterior cingulate cortex [ 55 ] or N-acetylaspartate to creatine ratio in the frontal and occipital cortex [ 57 ] have been reported.…”

“…Eight studies observed decreased global or regional CBF in ME/CFS [ 17 , 18 , 51 , 52 , 66 – 69 ]. Peterson et al observed reduced cerebral perfusion in 3 of 10 at rest and 6 of 10 patients with ME/CFS after an exercise of walking 1.61 km/hour for 30 min while only in 2 of 10 HCs at rest and post-exercise [ 70 ].…”

Insights from myalgic encephalomyelitis/chronic fatigue syndrome may help unravel the pathogenesis of postacute COVID-19 syndrome

“…• Increased nitrosative stress: increased levels of inducible nitric oxide synthase (iNOS), possibly secondary to increased production of NFκB [108]; increased nitric oxide (NO), peroxynitrite, and nitrate, particularly following exercise [109]. • Brain magnetic resonance imaging (MRI) has shown elevated levels of ventricular lactic acid consistent with oxidative stress [110,111].…”

The Enterovirus Theory of Disease Etiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Critical Review

“…ME/CFS patients have a number of pathophysiological traits that point to abnormalities in the ANS, including impaired blood pressure variability, orthostatic intolerance, high prevalence and severity of posturalorthostatic tachycardia syndrome (POTS), delayed gastric emptying, impaired thermoregulation in adolescent patients, loss of capacity to recover from acidosis on repeat exercise, abnormal cardiac output and altered brain characteristics in a wide variety of brain regions including the limbic system structures that govern the ANS (1,(78)(79)(80)(81). These altered brain characteristics include reduced cerebral, brainstem, and cerebral cortex blood flow; impaired reciprocal connectivity between the vasomotor center, midbrain, and hypothalamus regions; increased neuroinflammation across widely distributed brain areas including but not limited to the hippocampus, thalamus, midbrain and pons; reduced cerebral glucose metabolism, and lower brain glutathione (1,(82)(83)(84)(85)(86). Many of the altered brain characteristics seen in ME/CFS patients are similarly reported in clinical cases associated with neurotropic enteroviruses.…”