Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome

Abstract:

In October 2009, we reported the first direct isolation of infectious xenotropic murine leukemia virus-related virus (XMRV). In that study, we used a combination of biological amplification and molecular enhancement techniques to detect XMRV in more than 75% of 101 patients with chronic fatigue syndrome (CFS). Since our report, controversy arose after the publication of several studies that failed to detect XMRV infection in their CFS patient populations. In this addenda, we further detail the multiple detection methods we used in order to observe XMRV infection in our CFS cohort. Our results indicate that PCR from DNA of unstimulated peripheral blood mononuclear cells is the least sensitive method for detection of XMRV in subjects’ blood. We advocate the use of more than one type of assay in order to determine the frequency of XMRV infection in patient cohorts in future studies of the relevance of XMRV to human disease.

 

Source: Mikovits JA, Lombardi VC, Pfost MA, Hagen KS, Ruscetti FW. Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Virulence. 2010 Sep-Oct;1(5):386-90. doi: 10.4161/viru.1.5.12486. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073172/ (Full article)

 

Cerebral blood flow is reduced in chronic fatigue syndrome as assessed by arterial spin labeling

Abstract:

BACKGROUND: Chronic fatigue syndrome is diagnosed by a set of clinical criteria and therefore is probably heterogeneous. Earlier reports tested the hypothesis that the syndrome had a neurological substrate by doing studies of cerebral blood flow (CBF) but with discrepant results. One possible reason for the discrepancy was that relative CBF was assessed. We found reduced CBF in an earlier study of absolute CBF using xenon-CT. The purpose of this study was to use a second method of assessing CBF and to look within the study group for heterogeneity of responses.

METHOD: Eleven CFS patients and 10 age matched healthy controls underwent neuroimaging using arterial spin labeling to determine their regional and global absolute CBF. A template was constructed based on the control data, and individual patient montages were compared on a case by case basis to determine if differences in regions of interest occurred.

RESULTS: The patients as a group had significantly lower global CBF than the controls. The reduction in CBF occurred across nearly every region assessed. Nine of the 11 patients showed these reductions compared to the average control data, while two patients showed actual increases relative to the controls.

CONCLUSION: The data extend our earlier observation that CFS patients as a group have broad decreases in CBF compared to healthy controls. However, as expected, the effect was not homogeneous in that 2 of the 11 patients studied showed actual increases in CBF relative to controls.

Copyright © 2010 Elsevier B.V. All rights reserved.

 

Source: Biswal B, Kunwar P, Natelson BH. Cerebral blood flow is reduced in chronic fatigue syndrome as assessed by arterial spin labeling. J Neurol Sci. 2011 Feb 15;301(1-2):9-11. doi: 10.1016/j.jns.2010.11.018. Epub 2010 Dec 16.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139492/ (Full article)

 

Tired of being inactive: a systematic literature review of physical activity, physiological exercise capacity and muscle strength in patients with chronic fatigue syndrome

Abstract:

A systematic review was undertaken to examine whether patients with chronic fatigue syndrome (CFS) differ from healthy sedentary controls in physiological exercise capacity, physical activity level and muscle strength. From the available literature, it can be concluded that patients with CFS perform less physical activity during daily life, and have less peak isometric muscle strength compared to healthy sedentary control subjects. Conflicting data in relation to physiological exercise capacity of patients with CFS have been reported, but the weighted available evidence points towards a reduced physiological exercise capacity in CFS. Future studies should use a wash-out period for medication use, blinded assessments, a priori power calculation and a sedentary control group comparable for age, gender, body weight, body length and current physical activity level.

 

Source: Nijs J, Aelbrecht S, Meeus M, Van Oosterwijck J, Zinzen E, Clarys P. Tired of being inactive: a systematic literature review of physical activity, physiological exercise capacity and muscle strength in patients with chronic fatigue syndrome. Disabil Rehabil. 2011;33(17-18):1493-500. doi: 10.3109/09638288.2010.541543. Epub 2010 Dec 20. https://www.ncbi.nlm.nih.gov/pubmed/21166613

 

Nitric oxide concentrations are normal and unrelated to activity level in chronic fatigue syndrome: a case-control study

Abstract:

AIM: since patients with chronic fatigue syndrome (CFS) often present elevated levels of nitric oxide (NO) and low levels of physical activity, this study aimed at revealing possible correlations between NO concentration and physical activity.

PATIENTS AND METHODS: thirty CFS patients and 29 age- and gender-matched sedentary controls wore an accelerometer for one week and underwent venous blood sampling at the beginning and the end of the week.

RESULTS: CFS patients were significantly less active (p=0.001), but no significant differences in the amounts of NO (p=0.464 and 0.569) or interaction between NO levels and activity levels in either the CFS patients or controls were revealed.

CONCLUSION: these results provide further evidence for reduced activity levels in CFS patients, but refute there being any interaction between the amount of blood NO and activity level in both groups. The blood NO was neither predictive of, nor dependent on the activity level in CFS.

 

Source: Meeus M, VAN Eupen I, Hondequin J, DE Hauwere L, Kos D, Nijs J. Nitric oxide concentrations are normal and unrelated to activity level in chronic fatigue syndrome: a case-control study. In Vivo. 2010 Nov-Dec;24(6):865-9. https://www.ncbi.nlm.nih.gov/pubmed/21164046

 

No differences in cardiovascular autonomic responses to mental stress in chronic fatigue syndrome adolescents as compared to healthy controls

Abstract:

Chronic fatigue syndrome (CFS) is a disabling disease with unknown etiology. There is accumulating evidence of altered cardiovascular autonomic responses to different somatic stressors, in particular orthostatic stress, whereas autonomic responses to mental stress remain to be investigated. In this study, we explored cardiovascular autonomic responses to a simple mental stress test in CFS patients and healthy controls.

A consecutive sample of 13 patients with CFS, aged 12 to 18 years, and a volunteer sample of 53 healthy control subjects of equal age and gender distribution were included. Blood pressure, heart rate and acral skin blood flow were continuously recorded during an arithmetic exercise.

At baseline, heart rate was significantly higher among CFS patients than controls (p = 0.02). During the arithmetic exercise, however, there were no significant differences in the responses between the two groups.

In conclusion, CFS patients have unaltered autonomic responses to simple mental stress as compared to healthy control subjects.

 

Source: Egge C, Wyller VB. No differences in cardiovascular autonomic responses to mental stress in chronic fatigue syndrome adolescents as compared to healthy controls. Biopsychosoc Med. 2010 Dec 14;4:22. doi: 10.1186/1751-0759-4-22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012010/ (Full article)

 

The role of depression in cognitive impairment in patients with chronic fatigue syndrome

Abstract:

BACKGROUND AND OBJECTIVE: To analyze the role of depression in cognitive deficits of patients with chronic fatigue syndrome (CFS).

PATIENTS AND METHODS: 57 women with CFS were assessed by neuropsychological tests that included measures of attention: CalCap, Mental control of the WMS-III, PASAT, forward and backward digits (WAIS-III), symbol digit modalities test (SDMT); executive functions: Stroop Test, Trail Making Test (TMT A y B), FAS, Tower of London; memory: Auditory-Verbal Learning Test (AVL), Rey Complex Figure (RCF), and psychomotor skills: Grooved Pegboard. The raw scores on the tests were adjusted according to normative data and transformed to T scores. The sample was divided into two groups based on the presence or absence of depression, assessed by clinical interview and administration of the Hospital Anxiety and Depression Scale (HADS). This study compared neuropsychological test scores between the two groups.

RESULTS: CFS patients showed cognitive deficit in attention and executive functions, regardless of the presence of depression. There were no significant differences between the two CFS groups.

CONCLUSIONS: The cognitive impairments in patients with CFS are not secondary to the presence of depression. These results should be taken into account in the implementation of therapeutic programs in these patients.

Copyright © 2010 Elsevier España, S.L. All rights reserved.

 

Source: Santamarina-Pérez P, Freniche V, Eiroa-Orosa FJ, Llobet G, Sáez N, Alegre J, Jacas C. The role of depression in cognitive impairment in patients with chronic fatigue syndrome. Med Clin (Barc). 2011 Mar 12;136(6):239-43. doi: 10.1016/j.medcli.2010.07.022. Epub 2010 Dec 9. [Article in Spanish] https://www.ncbi.nlm.nih.gov/pubmed/21145567

 

The Newcastle NHS Chronic Fatigue Syndrome Service: not all fatigue is the same

Abstract:

In England the Department of Health has funded specialist clinical services aimed at diagnosing and managing the symptoms of chronic fatigue syndrome (CFS). These services are not available to those who do not fulfil the diagnostic criteria for CFS. This service evaluation examined the proportion of those referred to a specialist CFS service fulfilling the Fukuda diagnostic criteria for CFS and the alternative fatigue-associated diagnoses. The CFS database was interrogated to include every patient referred to the Newcastle service from November 2008 to December 2009. All medical notes were reviewed and the diagnosis, sex and age recorded. Data were compared to a previous service evaluation (2005-07).

In 2008-09, 260 subjects were referred: 19 referrals per month (260/14), compared with 17 referrals per month in 2005-07 (375/24). The proportion of patients diagnosed with CFS increased significantly compared with 2007 (36% [20/56] vs 60% [157/260]; p < 0.0001). Of the 40% of patients subsequently found not to have CFS the most common diagnosis was fatigue associated with a chronic disease (47% of all alternative diagnoses); 20% had primary sleep disorders, 15% psychological/psychiatric illnesses and 4% a cardiovascular disorder. Thirteen per cent remained unexplained (5.2% of the total referrals).

This study found a significant increase in the proportion of patients referred to National Health Service (NHS) CFS services diagnosed with CFS. A large proportion of patients presenting with fatigue are not eligible for referral to the Department of Health specialist fatigue services, which represents an unmet need in terms of symptom management in current NHS services.

 

Source: Newton JL, Mabillard H, Scott A, Hoad A, Spickett G. The Newcastle NHS Chronic Fatigue Syndrome Service: not all fatigue is the same. J R Coll Physicians Edinb. 2010 Dec;40(4):304-7. doi: 10.4997/JRCPE.2010.404. https://www.ncbi.nlm.nih.gov/pubmed/21132135

 

Frequency and content analysis of chronic fatigue syndrome in medical text books

Abstract:

Text books are a cornerstone in the training of medical staff and students, and they are an important source of references and reviews for these professionals. The objective of this study was to determine both the quantity and quality of chronic fatigue syndrome (CFS) information included in medical texts.

After reviewing 119 medical text books from various medical specialties, we found that 48 (40.3%) of the medical text books included information on CFS. However, among the 129 527 total pages within these medical text books, the CFS content was presented on only 116.3 (0.090%) pages. Other illnesses that are less prevalent, such as multiple sclerosis and Lyme disease, were more frequently represented in medical text books. These findings suggest that the topic of CFS is underreported in published medical text books.

 

Source: Jason LA, Paavola E, Porter N, Morello ML. Frequency and content analysis of chronic fatigue syndrome in medical text books. Aust J Prim Health. 2010;16(2):174-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691015/ (Full article)

 

Lipid peroxidation is elevated in female patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome is a debilitating disease of unclear cause and pathogenesis. It affects mostly women from lower socioeconomic classes. There is mounting evidence that oxidative stress, specifically lipid peroxidation (LPO) contributes to the disease process. We investigated levels of LPO and its possible consequences for these patients.

MATERIAL/METHODS: Forty women aged 15-45 years who fulfilled the 1994 Centers for Disease Control’s diagnostic criteria for chronic fatigue syndrome (CFS) with no comorbidities were recruited and were age matched to a control group of 40 healthy women. Levels of total cholesterol (TC), triglycerides (TG), LDL cholesterol (LDLc), HDL cholesterol (HDLc), and malondialdehyde (MDA) levels were measured.

RESULTS: Although initial statistical analyses showed no differences between groups (P=.345), when subdivided according to the level of MDA, a difference was found in the subgroup of high-level MDA (P=.034). There was a negative correlation between HDLc and MDA levels (r=0.3; P=.046), a positive correlation between TG and MDA levels (r=0.4; P=.006), and lower levels of HDL cholesterol in the CFS group (P=.036).

CONCLUSIONS: High levels of MDA, positively correlated with TG and lower HDL levels, might be indicative of proatherogenic events in female CFS patients, a group not otherwise considered a risk for atherosclerosis.

 

Source: Brkic S, Tomic S, Maric D, Novakov Mikic A, Turkulov V. Lipid peroxidation is elevated in female patients with chronic fatigue syndrome. Med Sci Monit. 2010 Dec;16(12):CR628-32. https://www.ncbi.nlm.nih.gov/pubmed/21119582

 

Making sense of fatigue: the need for a balanced approach

Dear Sir,

In their recent editorial on fatigue, Newton and Jones [1] comment that ‘the majority of primary care physicians believe that fatigue arises as a consequence of psychological rather than physical factors’ and imply that this may lead physicians to ‘fail before they begin’. They also go on to discuss a biological approach to the investigation and treatment of fatigue, highlighting the need to consider fatigue as ‘real’. While we agree with the need to consider biological processes in fatigued individuals, we contest that any approach that dichotomises the mind and body by focusing exclusively on either the biological or psychosocial aspects of fatigue ignores the current evidence base and is likely to be sub-optimal. We also strongly refute any suggestion that psychological disorders are any less ‘real’ than somatic conditions.

You can read the rest of this comment here: http://occmed.oxfordjournals.org/content/60/8/665.long

Comment on: Making sense of fatigue. [Occup Med (Lond). 2010]

 

Source: Harvey SB, Mykletun A, Wessely S. Making sense of fatigue: the need for a balanced approach. Occup Med (Lond). 2010 Dec;60(8):665-6; author reply 666-7. doi: 10.1093/occmed/kqq166. http://occmed.oxfordjournals.org/content/60/8/665.long (Full article)