Postural neurocognitive and neuronal activated cerebral blood flow deficits in young chronic fatigue syndrome patients with postural tachycardia syndrome

Abstract:

Neurocognition is impaired in chronic fatigue syndrome (CFS). We propose that the impairment relates to postural cerebral hemodynamics.

Twenty-five CFS subjects and twenty control subjects underwent incremental upright tilt at 0, 15, 30, 45, 60, and 75° with continuous measurement of arterial blood pressure and cerebral blood flow velocity (CBFV). We used an n-back task with n ranging from 0 to 4 (increased n = increased task difficulty) to test working memory and information processing. We measured n-back outcomes by the number of correct answers and by reaction time. We measured CBFV, critical closing pressure (CCP), and CBFV altered by neuronal activity (activated CBFV) during each n value and every tilt angle using transcranial Doppler ultrasound.

N-back outcome in control subjects decreased with n valve but was independent of tilt angle. N-back outcome in CFS subjects decreased with n value but deteriorated as orthostasis progressed. Absolute mean CBFV was slightly less than in control subjects in CFS subject at each angle. Activated CBFV in control subjects was independent of tilt angle and increased with n value.

In contrast, activated CBFV averaged 0 in CFS subjects, decreased with angle, and was less than in control subjects. CCP was increased in CFS subjects, suggesting increased vasomotor tone and decreased metabolic control of CBFV. CCP did not change with orthostasis in CFS subjects but decreased monotonically in control subjects, consistent with vasodilation as compensation for the orthostatic reduction of cerebral perfusion pressure.

Increasing orthostatic stress impairs neurocognition in CFS subjects. CBFV activation, normally tightly linked to cognitive neuronal activity, is unrelated to cognitive performance in CFS subjects; the increased CCP and vasomotor tone may indicate an uncoupling of the neurovascular unit during orthostasis.

 

Source: Stewart JM, Medow MS, Messer ZR, Baugham IL, Terilli C, Ocon AJ. Postural neurocognitive and neuronal activated cerebral blood flow deficits in young chronic fatigue syndrome patients with postural tachycardia syndrome. Am J Physiol Heart Circ Physiol. 2012 Mar 1;302(5):H1185-94. doi: 10.1152/ajpheart.00994.2011. Epub 2011 Dec 16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3311460/ (Full article)

 

Contrasting case definitions for chronic fatigue syndrome, Myalgic Encephalomyelitis/chronic fatigue syndrome and myalgic encephalomyelitis

Abstract:

This article uses data from patients recruited using the 1994 case definition of chronic fatigue syndrome (CFS) to contrast those meeting criteria for the Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS) Canadian case definition with those that did not meet these criteria. The study also contrasts those meeting criteria for Myalgic Encephalomyelitis (ME) based on criteria from Ramsay and other theorists with those that did not meet the ME criteria. The ME/CFS case definition criteria identified a subset of patients with more functional impairments and physical, mental, and cognitive problems than the subset not meeting these criteria. The ME subset had more functional impairments, and more severe physical and cognitive symptoms than the subset not meeting ME criteria. When applied to a population meeting the 1994 CFS case definition, both ME/CFS and ME criteria appear to select a more severe subset of patients.

 

Source: Jason LA, Brown A, Clyne E, Bartgis L, Evans M, Brown M. Contrasting case definitions for chronic fatigue syndrome, Myalgic Encephalomyelitis/chronic fatigue syndrome and myalgic encephalomyelitis. Eval Health Prof. 2012 Sep;35(3):280-304. doi: 10.1177/0163278711424281. Epub 2011 Dec 7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3658447/ (Full article)

 

Responses to exercise differ for chronic fatigue syndrome patients with fibromyalgia

Abstract:

Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are chronic multisymptom illnesses with substantial clinical and diagnostic overlap. We have previously shown that, when controlling for aerobic fitness and accounting for comorbid FM, CFS patients do not exhibit abnormal cardiorespiratory responses during maximal aerobic exercise compared with healthy controls, despite differences in pain and exertion.

PURPOSE: The purpose of the present study was to examine cardiac and perceptual responses to steady-state submaximal exercise in CFS patients and healthy controls.

METHODS: Twenty-one CFS patients (13 CFS with comorbid FM (CFS + FM)) and 14 controls completed 20 min of submaximal cycling exercise. Impedance cardiography was used to determine cardiac responses during exercise. Systolic blood pressure (SBP), RPE, and leg muscle pain were also measured. Data were analyzed using a doubly multivariate, repeated-measures MANOVA to model the exercise response.

RESULTS: There was a significant multivariate time-by-group interaction (P < 0.05). The CFS + FM group exhibited an exercise response characterized by higher stroke index, ventilatory equivalents for oxygen and carbon dioxide and RPE, lower SBP, and similar HR responses compared to controls.

CONCLUSIONS: The present results extend on our previous work with maximal exercise and show that CFS and CFS + FM differ in their responses to steady-state exercise. These results highlight the importance of accounting for comorbid conditions when conducting CFS research, particularly when examining psychophysiological responses to exercise.

 

Source: Cook DB, Stegner AJ, Nagelkirk PR, Meyer JD, Togo F, Natelson BH. Responses to exercise differ for chronic fatigue syndrome patients with fibromyalgia. Med Sci Sports Exerc. 2012 Jun;44(6):1186-93. doi: 10.1249/MSS.0b013e3182417b9a. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319493/ (Full article)

 

Unidentified Chronic Fatigue Syndrome/myalgic encephalomyelitis (CFS/ME) is a major cause of school absence: surveillance outcomes from school-based clinics

Abstract:

Objective To investigate the feasibility of conducting clinics for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in schools.

Design School-based clinical project. Participants Children aged 11-16 years were enrolled in three state secondary schools in England.

Main outcome measures Number of children newly diagnosed as having CFS/ME.

Methods Attendance officers identified children missing ≥20% of school in a 6-week term without a known cause, excluding those with a single episode off school, a known medical illness explaining the absence or known to be truanting. Children with fatigue were referred to a specialist CFS/ME service for further assessment. The authors compared children with CFS/ME identified through school-based clinics with those referred via health services. Outcomes of CFS/ME were evaluated at 6 weeks and 6 months.

Results 461 of the 2855 enrolled children had missed ≥20% school over a 6-week period. In 315, of whom three had CFS/ME, the reason for absence was known. 112 of the 146 children with unexplained absence attended clinical review at school; two had been previously diagnosed as having CFS/ME and 42 were referred on to a specialist clinic, where 23 were newly diagnosed as having CFS/ME. Therefore, 28 of the 2855 (1.0%) children had CFS/ME. Children with CFS/ME identified through surveillance had been ill for an amount of time comparable to those referred via health services but had less fatigue (mean difference 4.4, 95% CI 2.2 to 6.6), less disability (mean difference -5.7, 95% CI -7.9 to -3.5) and fewer symptoms (mean difference 1.86, 95% CI 0.8 to 2.93). Of 19 children followed up, six had fully recovered at 6 weeks and a further six at 6 months.

Conclusions Chronic fatigue is an important cause of unexplained absence from school. Children diagnosed through school-based clinics are less severely affected than those referred to specialist services and appear to make rapid progress when they access treatment.

 

Source: Crawley EM, Emond AM, Sterne JA. Unidentified Chronic Fatigue Syndrome/myalgic encephalomyelitis (CFS/ME) is a major cause of school absence: surveillance outcomes from school-based clinics. BMJ Open. 2011 Dec 12;1(2):e000252. doi: 10.1136/bmjopen-2011-000252. Print 2011. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3244656/ (Full article)

 

Molecular signatures of peripheral blood mononuclear cells during chronic interferon-α treatment: relationship with depression and fatigue

Abstract:

BACKGROUND: Interferon-alpha (IFN-α) treatment for infectious disease and cancer causes high rates of depression and fatigue, and has been used to investigate the impact of inflammatory cytokines on brain and behavior. However, little is known about the transcriptional impact of chronic IFN-α on immune cells in vivo and its relationship to IFN-α-induced behavioral changes.

METHOD: Genome-wide transcriptional profiling was performed on peripheral blood mononuclear cells (PBMCs) from 21 patients with chronic hepatitis C virus (HCV) either awaiting IFN-α therapy (n=10) or at 12 weeks of IFN-α treatment (n=11).

RESULTS: Significance analysis of microarray data identified 252 up-regulated and 116 down-regulated gene transcripts. Of the up-regulated genes, 2′-5′-oligoadenylate synthetase 2 (OAS2), a gene linked to chronic fatigue syndrome (CFS), was the only gene that was differentially expressed in patients with IFN-α-induced depression/fatigue, and correlated with depression and fatigue scores at 12 weeks (r=0.80, p=0.003 and r=0.70, p=0.017 respectively). Promoter-based bioinformatic analyses linked IFN-α-related transcriptional alterations to transcription factors involved in myeloid differentiation, IFN-α signaling, activator protein-1 (AP1) and cAMP responsive element binding protein/activation transcription factor (CREB/ATF) pathways, which were derived primarily from monocytes and plasmacytoid dendritic cells. IFN-α-treated patients with high depression/fatigue scores demonstrated up-regulation of genes bearing promoter motifs for transcription factors involved in myeloid differentiation, IFN-α and AP1 signaling, and reduced prevalence of motifs for CREB/ATF, which has been implicated in major depression.

CONCLUSIONS: Depression and fatigue during chronic IFN-α administration were associated with alterations in the expression (OAS2) and transcriptional control (CREB/ATF) of genes linked to behavioral disorders including CFS and major depression, further supporting an immune contribution to these diseases.

 

Source: Felger JC, Cole SW, Pace TW, Hu F, Woolwine BJ, Doho GH, Raison CL, Miller AH. Molecular signatures of peripheral blood mononuclear cells during chronic interferon-α treatment: relationship with depression and fatigue. Psychol Med. 2012 Aug;42(8):1591-603. doi: 10.1017/S0033291711002868. Epub 2011 Dec 9.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3433045/ (Full article)

 

Regional grey and white matter volumetric changes in myalgic encephalomyelitis (chronic fatigue syndrome): a voxel-based morphometry 3 T MRI study

Abstract:

OBJECTIVE: It is not established whether myalgic encephalomyelitis/chronic fatigue syndrome (CFS) is associated with structural brain changes. The aim of this study was to investigate this by conducting the largest voxel-based morphometry study to date in CFS.

METHODS: High-resolution structural 3 T cerebral MRI scanning was carried out in 26 patients with CFS and 26 age- and gender-matched healthy volunteers. Voxel-wise generalised linear modelling was applied to the processed MR data using permutation-based non-parametric testing, forming clusters at t>2.3 and testing clusters for significance at p<0.05, corrected for multiple comparisons across space.

RESULTS: Significant voxels (p<0.05, corrected for multiple comparisons) depicting reduced grey matter volume in the CFS group were noted in the occipital lobes (right and left occipital poles; left lateral occipital cortex, superior division; and left supracalcrine cortex), the right angular gyrus and the posterior division of the left parahippocampal gyrus. Significant voxels (p<0.05, corrected for multiple comparisons) depicting reduced white matter volume in the CFS group were also noted in the left occipital lobe.

CONCLUSION: These data support the hypothesis that significant neuroanatomical changes occur in CFS, and are consistent with the complaint of impaired memory that is common in this illness; they also suggest that subtle abnormalities in visual processing, and discrepancies between intended actions and consequent movements, may occur in CFS.

 

Source: Puri BK, Jakeman PM, Agour M, Gunatilake KD, Fernando KA, Gurusinghe AI, Treasaden IH, Waldman AD, Gishen P. Regional grey and white matter volumetric changes in myalgic encephalomyelitis (chronic fatigue syndrome): a voxel-based morphometry 3 T MRI study. Br J Radiol. 2012 Jul;85(1015):e270-3. doi: 10.1259/bjr/93889091. Epub 2011 Nov 29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3474083/ (Full article)

 

Small heart with low cardiac output for orthostatic intolerance in patients with chronic fatigue syndrome

Abstract:

BACKGROUND: The etiology of chronic fatigue syndrome (CFS) is unknown. Orthostatic intolerance (OI) is common in CFS patients. Recently, small heart with low cardiac output has been postulated to be related to the genesis of both CFS and OI.

HYPOTHESIS: Small heart is associated with OI in patients with CFS.

METHODS: Study CFS patients were divided into groups of 26 (57%) CFSOI(+) and 20 (43%) CFSOI(-) according to the presence or absence of OI. In addition, 11 OI patients and 27 age- and sex-matched control subjects were studied. Left ventricular (LV) dimensions and function were determined echocardiographically.

RESULTS: The mean values of cardiothoracic ratio, systemic systolic and diastolic pressures, LV end-diastolic dimension, LV end-systolic dimension, stroke volume index, cardiac index, and LV mass index were all significantly smaller in CFSOI(+) patients than in CFSOI(-) patients and healthy controls, and also in OI patients than in controls. A smaller LV end-diastolic dimension (<40 mm) was significantly (P<0.05) more prevalently noted in CFSOI(+) (54%) and OI (45%) than in CFSOI(-) (5%) and controls (4%). A lower cardiac index (<2 L/min/mm(2)) was more prevalent in CFSOI(+) (65%) than in CFSOI(-) (5%, P<0.01), OI (27%), and controls (11%, P<0.01).

CONCLUSIONS: A small size of LV with low cardiac output was noted in OI, and its degree was more pronounced in CFSOI(+). A small heart appears to be related to the genesis of OI and CFS via both cerebral and systemic hypoperfusion. CFSOI(+) seems to constitute a well-defined and predominant subgroup of CFS.

© 2011 Wiley Periodicals, Inc.

 

Source: Miwa K, Fujita M. Small heart with low cardiac output for orthostatic intolerance in patients with chronic fatigue syndrome. Clin Cardiol. 2011 Dec;34(12):782-6. doi: 10.1002/clc.20962. Epub 2011 Nov 28. http://onlinelibrary.wiley.com/doi/10.1002/clc.20962/full (Full article)

 

The role of acceptance in chronic fatigue syndrome

Abstract:

OBJECTIVE: In this paper we consider the role that acceptance plays in fatigue and physical and social functioning. We predicted that lack of acceptance would be positively correlated with fatigue and impairment in functioning; that there would be a significant relationship between perfectionism and acceptance; and cognitive behavioural therapy (CBT) would increase acceptance.

METHODS: Two hundred and fifty nine patients with chronic fatigue syndrome (CFS) completed questionnaires measuring fatigue, physical functioning, work and social adjustment, lack of acceptance, perfectionism and depression. Ninety consecutive attenders received a course of CBT and completed further questionnaires at discharge and 3months post-treatment. Correlations and multiple hierarchical regressions were used to determine relationships between acceptance, perfectionism and clinical outcome variables.

RESULTS: At baseline, lack of acceptance was the key factor associated with impaired physical functioning and work and social adjustment. Lack of acceptance and doubts about actions were associated with fatigue in a multiple regression analysis. At discharge and follow-up patients showed significantly increased acceptance, as well as reduced Concern over Mistakes, less fatigue and impairment of physical functioning, and improved work and social adjustment.

CONCLUSION: This is the first study to our knowledge which shows a change in acceptance after CBT and a relationship between acceptance and perfectionism. Acceptance may be an important factor to consider within treatments for CFS.

2011 Elsevier Inc. All rights reserved.

 

Source: Brooks SK, Rimes KA, Chalder T. The role of acceptance in chronic fatigue syndrome. J Psychosom Res. 2011 Dec;71(6):411-5. doi: 10.1016/j.jpsychores.2011.08.001. Epub 2011 Sep 16. https://www.ncbi.nlm.nih.gov/pubmed/22118384

 

Childhood maltreatment and the response to cognitive behavior therapy for chronic fatigue syndrome

Abstract:

OBJECTIVE: To examine the relationship between a history of childhood maltreatment and the treatment response to cognitive behavior therapy for chronic fatigue syndrome (CFS).

METHODS: A cohort study in a tertiary care clinic with a referred sample of 216 adult patients meeting the Centers for Disease Control and Prevention criteria for CFS, and starting cognitive behavior therapy. Main outcome measures changes between pre- and post therapy in fatigue (Checklist Individual Strength fatigue subscale), disabilities (Sickness Impact Profile total score), physical functioning (short form 36 health survey subscale) and psychological distress (Symptom checklist 90 total score).

RESULTS: At baseline, patients with a history of childhood maltreatment had significantly more limitations and a higher level of psychological distress, but were not more severely fatigued. Change scores on the outcome measures after cognitive behavior therapy did not differ significantly between patients with or without a history of childhood maltreatment, or between the different types of childhood maltreatment. However, patients with a history of childhood maltreatment still experienced more limitations and a higher level of psychological distress after CBT.

CONCLUSIONS: A history of childhood maltreatment was not related to the treatment response of cognitive behavior therapy for CFS. In patients with a history of childhood maltreatment CFS symptoms can be treated with CBT just as well as those without.

2011 Elsevier Inc. All rights reserved.

 

Source: Heins MJ, Knoop H, Lobbestael J, Bleijenberg G. Childhood maltreatment and the response to cognitive behavior therapy for chronic fatigue syndrome. J Psychosom Res. 2011 Dec;71(6):404-10. doi: 10.1016/j.jpsychores.2011.05.005. Epub 2011 Jun 30. https://www.ncbi.nlm.nih.gov/pubmed/22118383

 

Up-regulation of TGF-β1 mRNA expression in peripheral blood mononuclear cells of patients with chronic fatigue syndrome

Abstract:

BACKGROUND/PURPOSE: It has been shown that the abnormality in immune cells in chronic fatigue syndrome (CFS) patients is closely associated with the participation of TGF-β. In order to study the relationship between TGF-β1 and CFS, we investigated the mRNA levels of TGF-β1 in peripheral blood mononuclear cells (PBMCs) in patients with CFS.

METHODS: Fluorescent quantitative real time reverse-transcription polymerase chain reaction (FQ-RT-PCR) was performed to test TGF-β1 mRNA expression in PBMCs in 63 cases of CFS, 50 cases of disease controls, and 50 cases of healthy controls.

RESULTS: The mean value of TGF-β1 mRNA expression in CFS patients was ΔΔCt=1.17±0.58, which was significantly higher than the disease controls (ΔΔCt=0.07±1.08, df=111, p < 0.01) and the healthy controls (ΔΔCt=0.00±1.63, df=111, p < 0.01). No significant difference was detected between disease and healthy controls (p > 0.05).

CONCLUSION: The expression of TGF-β1 in PBMCs is significantly elevated in patients with CFS. It might be correlated to the pathogenesis of the disease.

Copyright © 2011. Published by Elsevier B.V.

 

Source: Zhang HY, Liu ZD, Hu CJ, Wang DX, Zhang YB, Li YZ. Up-regulation of TGF-β1 mRNA expression in peripheral blood mononuclear cells of patients with chronic fatigue syndrome. J Formos Med Assoc. 2011 Nov;110(11):701-4. doi: 10.1016/j.jfma.2011.09.006. Epub 2011 Oct 22. http://www.jfma-online.com/article/S0929-6646(11)00070-2/fulltext (Full article)