Analysis of cerebrospinal fluid from chronic fatigue syndrome patients for multiple human ubiquitous viruses and xenotropic murine leukemia-related virus

Abstract:

Recent reports showed many patients with chronic fatigue syndrome (CFS) harbor a retrovirus, xenotropic murine leukemia-related virus (XMRV), in blood; other studies could not replicate this finding. A useful next step would be to examine cerebrospinal fluid, because in some patients CFS is thought to be a brain disorder. Finding a microbe in the central nervous system would have greater significance than in blood because of the integrity of the blood-brain barrier. We examined cerebrospinal fluid from 43 CFS patients using polymerase chain reaction techniques, but did not find XMRV or multiple other common viruses, suggesting that exploration of other causes or pathogenetic mechanisms is warranted.

Copyright © 2011 American Neurological Association.

Comment in:

Reply to Schutzer et al. [Ann Neurol. 2011]

Extraordinary claims require extraordinary evidence. [Ann Neurol. 2011]

 

Source: Schutzer SE, Rounds MA, Natelson BH, Ecker DJ, Eshoo MW. Analysis of cerebrospinal fluid from chronic fatigue syndrome patients for multiple human ubiquitous viruses and xenotropic murine leukemia-related virus. Ann Neurol. 2011 Apr;69(4):735-8. doi: 10.1002/ana.22389. Epub 2011 Apr 6. https://www.ncbi.nlm.nih.gov/pubmed/21472770

 

Excess of activating killer cell immunoglobulin‑like receptors and lack of HLA-Bw4 ligands: a two‑edged weapon in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is an inflammatory disease of unknown aetiology. Researchers have proposed infectious, neurological and immunological causes of this syndrome. Recently, the xenotropic murine leukemia virus-related virus was detected in 67% of patients with CFS in a US study. This observation is in agreement with one ascertained aspect of the disease: a decreased efficiency in NK cell lytic activity in CFS patients. Here, we analyzed the genomic polymorphism of killer cell immunoglobulin-like receptors (KIRs) and their HLA class I cognate ligands in patients with certified CFS. An excess of KIR3DS1 was found in CFS patients with respect to controls, as well as an increased frequency of the genotype missing KIR2DS5. Forty-four CFS patients and 50 controls also underwent genomic typing for the HLA-ligands. In the patients, a great proportion of KIR3DL1 and KIR3DS1 receptors were found to be missing their HLA-Bw4Ile80 binding motif. We hypothesize that an excess of KIR3DS1, combined with an excess of ligand-free KIR3DL1 and KIR3DS1 receptors, may hamper the clearance of a pathogen via NK cells, thus favouring the chronicity of the infection.

Source: Pasi A, Bozzini S, Carlo-Stella N, Martinetti M, Bombardieri S, De Silvestri A, Salvaneschi L, Cuccia M. Excess of activating killer cell immunoglobulin‑like receptors and lack of HLA-Bw4 ligands: a two‑edged weapon in chronic fatigue syndrome. Mol Med Rep. 2011 May-Jun;4(3):535-40. doi: 10.3892/mmr.2011.447. Epub 2011 Mar 4. https://www.ncbi.nlm.nih.gov/pubmed/21468604

Self-critical perfectionism, stress generation, and stress sensitivity in patients with chronic fatigue syndrome: relationship with severity of depression

Abstract:

Chronic Fatigue Syndrome (CFS) is a highly disabling disorder that is part of a broader spectrum of chronic pain and fatiguedisorders. Although the etiology and pathogenesis of CFS largely remain unclear, there is increasing evidence that CFS shares important pathophysiological disturbances with mood disorders in terms of disturbances in the stress response and the stress system.

From a psycho-dynamic perspective, self-critical perfectionism and related personality factors are hypothesized to explain in part impairments of the stress response in both depression and CFS. Yet, although there is ample evidence that high levels of self-critical perfectionism are associated with stress generation and increased stress sensitivity in depression, evidence supporting this hypothesis in CFS is currently lacking.

This study therefore set out to investigate the relationship between self-critical perfectionism, the active generation of stress, stress sensitivity, and levels of depression in a sample of 57 patients diagnosed with CFS using an ecological momentary assessment approach.

Results showed, congruent with theoretical assumptions, that self-critical perfectionism was associated with the generation of daily hassles, which in turn predicted higher levels of depression. Moreover, multilevel analyses showed that self-critical perfectionism was related to increased stress sensitivity in CFS patients over a 14-day period, and that increased stress sensitivity in turn was related to increased levels of depression. The implications of these findings for future research and particularly for the development of psychodynamic treatment approaches of CFS and related conditions are discussed.

 

Source: Luyten P, Kempke S, Van Wambeke P, Claes S, Blatt SJ, Van Houdenhove B. Self-critical perfectionism, stress generation, and stress sensitivity in patients with chronic fatigue syndrome: relationship with severity of depression. Psychiatry. 2011 Spring;74(1):21-30. doi: 10.1521/psyc.2011.74.1.21. https://www.ncbi.nlm.nih.gov/pubmed/21463167

 

The cerebralization of fatigue: an analysis of the cerebral hypothesis in the case of chronic fatigue syndrome

Abstract:

The article analyzes a number of conditions that allowed the brain to become established as an etiological hypothesis in the case of chronic fatigue syndrome (CFS), together with other hypotheses related to organic causes, such as viruses and immunity. It also addresses the process of cerebralization of personhood, which grew out of the use of neuroimaging for research and diagnostic purposes and according to which the brain constitutes the prime place for looking for the cause of the diseases – including CFS – within the context of a somatic culture, intensified at the end of the twentieth century.

 

Source: Ortega F, Zorzanelli R. The cerebralization of fatigue: an analysis of the cerebral hypothesis in the case of chronic fatigue syndrome. Hist Cienc Saude Manguinhos. 2010 Jun;17(2):289-305. [Article in Portuguese] http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0104-59702010000200002&lng=en&nrm=iso&tlng=en (Full article)

 

Psychopathology and physical activity as predictors of chronic fatigue syndrome in the 1958 british birth cohort: a replication study of the 1946 and 1970 birth cohorts

Abstract:

PURPOSE: In this study, we investigate whether prospective associations between psychopathology, physical activity, and chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) observed in the 1946 and 1970 birth cohorts were replicable in the 1958 British birth cohort.

METHODS: Prospective study using the 1958 British birth cohort, which included 98.7% of births from 1 week in March 1958 in England, Wales, and Scotland. The outcome was self-reported CFS/ME by the age of 42 years, at which point 11,419 participants remained in the study. Psychopathology was assessed by the Rutter scales in childhood and the Malaise Inventory in adulthood. Physical activity was reported by the cohort member, mother and teacher in childhood and adulthood.

RESULTS: The prevalence of CFS/ME was 1.0% (95% confidence interval [CI] = 0.9-1.3) and the median age of onset was 34 years. Premorbid psychopathology at 23 years (odds ratio [OR] = 1.85, 95% CI = 1.06-3.22) and 33 years (OR = 2.81, 95% CI = 1.28-6.18) significantly increased the odds of developing CFS/ME, supporting the 1946 cohort findings. Childhood psychopathology, sedentary behavior in childhood, and persistent exercise in adulthood were not associated with CFS/ME.

CONCLUSIONS: In cohort studies premorbid psychopathology in adulthood is a replicated risk marker for CFS/ME, whereas premorbid extremes of physical activity are not.

Copyright © 2011 Elsevier Inc. All rights reserved.

 

Source: Goodwin L, White PD, Hotopf M, Stansfeld SA, Clark C. Psychopathology and physical activity as predictors of chronic fatigue syndrome in the 1958 British birth cohort: a replication study of the 1946 and 1970 birth cohorts. Ann Epidemiol. 2011 May;21(5):343-50. doi: 10.1016/j.annepidem.2010.12.003. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078325/ (Full article)

 

Factors influencing engagement of patients in a novel intervention for CFS/ME: a qualitative study.

Abstract:

AIM: To establish what factors are important for patients to engage in a new intervention for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and make recommendations to general practitioners (GPs) on preparing a patient for referral to such a service.

BACKGROUND: NICE guidelines recommend a prominent role for primary care in the management of patients with CFS/ME, with prompt diagnosis and appropriate referral for evidence-based treatments.

METHODS: A qualitative study nested within a multi-centre randomised controlled trial of two new nurse therapist delivered interventions. Semi-structured interviews carried out with 19 patients who had received pragmatic rehabilitation (PR) in the trial. Interviews were transcribed verbatim and an iterative approach used to develop themes from the data set.

FINDINGS:Factors that influence whether or not a patient engages with PR for CFS/ME are ensuring that the patient feels accepted and believed, that they accept the diagnosis, and that the model implicated by the treatment offered to the patient matches the model of illness held by the patient. If patients hold a clearly incompatible model of their illness, it is unlikely that they will engage with, and successfully complete, therapy. It is vital that the GP elicits and explores such illness beliefs either before making a referral to maximise patient engagement in therapy, or that an initial session with the therapist explores attitudes to the treatment model offered and then works with the patient’s model.

 

Source: Chew-Graham C, Brooks J, Wearden A, Dowrick C, Peters S. Factors influencing engagement of patients in a novel intervention for CFS/ME: a qualitative study. Prim Health Care Res Dev. 2011 Apr;12(2):112-22. doi: 10.1017/S146342361000037X. https://www.ncbi.nlm.nih.gov/pubmed/21457596

 

Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Abstract:

BACKGROUND: There is evidence that myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by activation of immune, inflammatory, oxidative and nitrosative stress (IO&NS) pathways. The present study was carried out in order to examine whether ME/CFS is accompanied by increased levels of plasma peroxides and serum oxidized LDL (oxLDL) antibodies, two biomarkers of oxidative stress.

MATERIAL/METHODS: Blood was collected from 56 patients with ME/CFS and 37 normal volunteers. Severity of ME/CFS was measured using the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale.

RESULTS: Plasma peroxide concentrations were significantly higher in patients with ME/CFS than in normal controls. There was a trend towards significantly higher serum oxLDL antibodies in ME/CFS than in controls. Both biomarkers contributed significantly in discriminating between patients with ME/CFS and normal controls. Plasma peroxide and serum oxLDL antibody levels were both significantly related to one of the FF symptoms.

CONCLUSIONS: The results show that ME/CFS is characterized by increased oxidative stress.

 

Source: Maes M, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E. Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Med Sci Monit. 2011 Apr;17(4):SC11-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539515/ (Full article)

Decades of delayed diagnosis in 4 levodopa-responsive young-onset monogenetic parkinsonism patients

Abstract:

BACKGROUND: We report 4 patients with young-onset monogenetic parkinsonism, each of whom was misdiagnosed with either a psychogenic movement disorder or chronic fatigue syndrome for 10 to 23 years after the onset of their first symptoms.

RESULTS: Once the diagnosis was eventually made, they all had a rapid and excellent response to levodopa, albeit with the early appearance of interdose dyskinesias in 3.

CONCLUSIONS: We discuss possible reasons for the missed diagnosis despite the relentless progression of their motor handicap. DAT scanning supported the revised clinical diagnosis of parkinsonism.

Copyright © 2011 Movement Disorder Society.

 

Source: Ling H, Braschinsky M, Taba P, Lüüs SM, Doherty K, Hotter A, Poewe W, Lees AJ. Decades of delayed diagnosis in 4 levodopa-responsive young-onset monogenetic parkinsonism patients. Mov Disord. 2011 Jun;26(7):1337-40. doi: 10.1002/mds.23563. Epub 2011 Mar 29. https://www.ncbi.nlm.nih.gov/pubmed/21449012

 

Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study

Abstract:

BACKGROUND: The long term adverse effects of Severe Acute Respiratory Syndrome (SARS), a viral disease, are poorly understood.

METHODS: Sleep physiology, somatic and mood symptoms of 22 Toronto subjects, 21 of whom were healthcare workers, (19 females, 3 males, mean age 46.29 yrs.+/- 11.02) who remained unable to return to their former occupation (mean 19.8 months, range: 13 to 36 months following SARS) were compared to 7 healthy female subjects. Because of their clinical similarities to patients with fibromyalgia syndrome (FMS) these post-SARS subjects were similarly compared to 21 drug free female patients, (mean age 42.4 +/- 11.8 yrs.) who fulfilled criteria for fibromyalgia.

RESULTS: Chronic post-SARS is characterized by persistent fatigue, diffuse myalgia, weakness, depression, and nonrestorative sleep with associated REM-related apneas/hypopneas, an elevated sleep EEG cyclical alternating pattern, and alpha EEG sleep anomaly. Post- SARS patients had symptoms of pre and post-sleep fatigue and post sleep sleepiness that were similar to the symptoms of patients with FMS, and similar to symptoms of patients with chronic fatigue syndrome. Both post-SARS and FMS groups had sleep instability as indicated by the high sleep EEG cyclical alternating pattern rate. The post-SARS group had a lower rating of the alpha EEG sleep anomaly as compared to the FMS patients. The post-SARS group also reported less pre-sleep and post-sleep musculoskeletal pain symptoms.

CONCLUSIONS: The clinical and sleep features of chronic post-SARS form a syndrome of chronic fatigue, pain, weakness, depression and sleep disturbance, which overlaps with the clinical and sleep features of FMS and chronic fatigue syndrome.

 

Source: Moldofsky H, Patcai J. Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study. BMC Neurol. 2011 Mar 24;11:37. doi: 10.1186/1471-2377-11-37. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071317/ (Full article)

 

Chronic fatigue syndrome in an ethnically diverse population: the influence of psychosocial adversity and physical inactivity

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a complex multifactorial disorder. This paper reports the prevalence of chronic fatigue (CF) and CFS in an ethnically diverse population sample and tests whether prevalence varies by social adversity, social support, physical inactivity, anxiety and depression.

METHODS: Analysis of survey data linking the Health Survey for England (1998 and 1999) and the Ethnic Minority Psychiatric Illness Rates in the Community (EMPIRIC) study undertaken in 2000. The study population comprised a national population sample of 4,281 people ages 16 to 74 years. CF and CFS were operationally defined on the basis of an interview in the EMPIRIC study, alongside questions about psychosocial risk factors. Previous illnesses were reported in the Health Survey for England during 1998 and 1999, as was physical inactivity.

RESULTS: All ethnic minority groups had a higher prevalence of CFS than the White group. The lowest prevalence was 0.8% in the White group, and it was highest at 3.5% in the Pakistani group (odds ratio (OR), 4.1; 95% confidence interval (95% CI), 1.6 to 10.4). Anxiety (OR, 1.8; 95% CI, 1.4 to 2.2), depression (OR, 1.4; 95% CI, 1.1 to 1.8), physical inactivity (OR, 2.0; 95% CI, 1.1 to 3.8), social strain (OR, 1.24; 95% CI, 1.04 to 1.48) and negative aspects of social support (OR, 2.12; 95% CI, 1.4 to 3.3) were independent risk factors for CFS in the overall sample. Together these risk factors explained ethnic differences in the prevalence of CFS, but no single risk factor could explain a higher prevalence in all ethnic groups.

CONCLUSIONS: The prevalence of CFS, but not CF, varies by ethnic group. Anxiety, depression, physical inactivity, social strain and negative aspects of social support together accounted for prevalence differences of CFS in the overall sample.

 

Source: Bhui KS, Dinos S, Ashby D, Nazroo J, Wessely S, White PD. Chronic fatigue syndrome in an ethnically diverse population: the influence of psychosocial adversity and physical inactivity. BMC Med. 2011 Mar 21;9:26. doi: 10.1186/1741-7015-9-26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3072345/ (Full article)