Chronic fatigue syndrome/myalgic encephalomyelitis: an update

Abstract:

Chronic Fatigue Syndrome (CFS), also referred to as Myalgic Encephalomyelitis (ME), is a disease of unknown origin. It is classified as Post Viral Fatigue Syndrome (PVFS) in the WHO International Classification of Diseases (ICD) and listed as sub-category at G93.3 under chapter G93, other disorders of the brain. ME/CFS is primarily an endemic disorder but occurs in both epidemic and sporadic forms. It affects all racial-ethnic groups and is seen in all socioeconomic strata. A diagnosis of CFS is a diagnosis of exclusion, meaning other medical conditions, including psychiatric disorders, must be first ruled out. CFS is diagnosed if there is no other explanation for the fatigue and if the other symptoms did not develop before the fatigue. The estimated worldwide prevalence of CFS is 0.4?1 percent. The disease predominantly affects young adults, with a peak age of onset of between 20 and 40 years, and women, with a female to male ratio of 6:1. Mean illness duration ranges from 3 to 9 years.

The patho-physiological mechanism of CFS is unclear but the immunological pattern of CFS patients gleaned from various studies indicates that the immune system is chronically activated. Besides the role of environmental insults (xenobiotics, infectious agents, stress) the genetic features of patients are studied to evaluate their role in triggering the pathology. At present there are no specific pharmacological therapies to treat the disease but a variety of therapeutic approaches have been described as benefiting patients. Treatment programs are directed at relief of symptoms, with the goal of the patient regaining some level of preexisting function and well-being.

 

Source: Capelli E, Zola R, Lorusso L, Venturini L, Sardi F, Ricevuti G. Chronic fatigue syndrome/myalgic encephalomyelitis: an update. Int J Immunopathol Pharmacol. 2010 Oct-Dec;23(4):981-9. https://www.ncbi.nlm.nih.gov/pubmed/21244747

 

Health-related quality of life in patients with chronic fatigue syndrome: group cognitive behavioural therapy and graded exercise versus usual treatment. A randomised controlled trial with 1 year of follow-up

Abstract:

Chronic fatigue syndrome (CFS) produces physical and neurocognitive disability that significantly affects health-related quality of life (HRQL). Multidisciplinary treatment combining graded exercise therapy (GET) cognitive behavioural therapy (CBT) and pharmacological treatment has shown only short-term improvements.

Aim: To compare the effects on HRQL of (1) multidisciplinary treatment combining CBT, GET, and pharmacological treatment, and (2) usual treatment (exercise counselling and pharmacological treatment) at 12 months of follow-up.

Design: Prospective, randomized controlled trial with a follow-up of 12 months after the end of treatment.

Method: Patients consecutively diagnosed with CFS (Fukuda criteria) were randomly assigned to intervention (n = 60) or usual treatment (n = 60) groups. HRQL was assessed at baseline and 12 months by the Medical Outcomes Study Short-Form questionnaire (SF-36). Secondary outcomes included functional capacity for activities of daily living measured by the Stanford Health Assessment Questionnaire (HAQ) and comorbidities.

Results: At baseline, the two groups were similar, except for lower SF-36 emotional role scores in the intervention group. At 12 months, the intervention did not improve HRQL scores, with worse SF-36 physical function and bodily pain scores in the intervention group.

Conclusion: Multidisciplinary treatment was not superior to usual treatment at 12 months in terms of HRQL. The possible benefits of GET as part of multidisciplinary treatment for CFS should be assessed on an individual patient basis.

 

Source: Núñez M, Fernández-Solà J, Nuñez E, Fernández-Huerta JM, Godás-Sieso T, Gomez-Gil E. Health-related quality of life in patients with chronic fatigue syndrome: group cognitive behavioural therapy and graded exercise versus usual treatment. A randomised controlled trial with 1 year of follow-up. Clin Rheumatol. 2011 Mar;30(3):381-9. doi: 10.1007/s10067-010-1677-y. Epub 2011 Jan 15. https://www.ncbi.nlm.nih.gov/pubmed/21234629

For a list of references see: http://link.springer.com/article/10.1007/s10067-010-1677-y

 

CFS prevalence and risk factors over time

Abstract:

The present natural history study examined the course of CFS from 1995-97 (Wave 1) to approximately 10 years later (Wave 2) from a random, community-based, multi-ethnic population. The rate of CFS remained approximately the same over the period of time from Wave 1 to Wave 2, although a high level of mortality was found (18% of those with medical or psychiatric exclusions group, 12.5% for the CFS group). Physical measures of disability and fatigue, along with measures of specific somatic symptoms, better differentiate individuals who later are diagnosed with CFS than more psychosocial measures such as stress and coping.

 

Source: Jason LA, Porter N, Hunnell J, Rademaker A, Richman JA. CFS prevalence and risk factors over time. J Health Psychol. 2011 Apr;16(3):445-56. doi: 10.1177/1359105310383603. Epub 2011 Jan 11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166209/ (Full article)

 

Diagnostic accuracy of symptoms characterising chronic fatigue syndrome

Abstract:

PURPOSE: To determine the diagnostic accuracy for single symptoms and clusters of symptoms to distinguish between individuals with and without chronic fatigue syndrome (CFS).

METHODS: A cohort study was conducted in an exercise physiology laboratory in an academic setting. Thirty subjects participated in this study (n = 16 individuals with CFS; n = 14 non-disabled sedentary matched control subjects). An open-ended symptom questionnaire was administered 1 week following the second of two maximal cardiopulmonary exercise tests administered 24 h apart.

RESULTS: Receiver operating characteristics (ROC) curve analysis was significant for failure to recover within 1 day (area under the curve  =  0.864, 95% confidence interval [CI]: 0.706-1.00, p = 0.001) but not within 7 days. Clinimetric properties of failure to recover within 1 day to predict membership in the CFS cohort were sensitivity 0.80, specificity 0.93, positive predictive value 0.92, negative predictive value 0.81, positive likelihood ratio 11.4, and negative likelihood ratio 0.22. Fatigue demonstrated high sensitivity and modest specificity to distinguish between cohorts, while neuroendocrine dysfunction, immune dysfunction, pain, and sleep disturbance demonstrated high specificity and modest sensitivity. ROC analysis suggested cut-point of three associated symptoms (0.871, 95% CI: 0.717-1.00, p < 0.001). A significant binary logistic regression model (p < 0.001) revealed immune abnormalities, sleep disturbance and pain accurately classified 92% of individuals with CFS and 88% of control subjects.

CONCLUSIONS: A cluster of associated symptoms distinguishes between individuals with and without CFS. Fewer associated symptoms may be necessary to establish a diagnosis of CFS than currently described.

 

Source: Davenport TE, Stevens SR, Baroni K, Van Ness M, Snell CR. Diagnostic accuracy of symptoms characterising chronic fatigue syndrome. Disabil Rehabil. 2011;33(19-20):1768-75. doi: 10.3109/09638288.2010.546936. Epub 2011 Jan 6. https://www.ncbi.nlm.nih.gov/pubmed/21208154

 

Long-chain acylcarnitine deficiency in patients with chronic fatigue syndrome. Potential involvement of altered carnitine palmitoyltransferase-I activity

Abstract:

OBJECTIVE: The underlying aetiology of chronic fatigue syndrome is currently unknown; however, in the light of carnitine’s critical role in mitochondrial energy production, it has been suggested that chronic fatigue syndrome may be associated with altered carnitine homeostasis. This study was conducted to comparatively examine full endogenous carnitine profiles in patients with chronic fatigue syndrome and healthy controls.

DESIGN: A cross-sectional, observational study.

SETTING AND SUBJECTS: Forty-four patients with chronic fatigue syndrome and 49 age- and gender-matched healthy controls were recruited from the community and studied at the School of Pharmacy & Medical Sciences, University of South Australia.

MAIN OUTCOME MEASURES: All participants completed a fatigue severity scale questionnaire and had a single fasting blood sample collected which was analysed for l-carnitine and 35 individual acylcarnitine concentrations in plasma by LC-MS/MS.

RESULTS: Patients with chronic fatigue syndrome exhibited significantly altered concentrations of C8:1, C12DC, C14, C16:1, C18, C18:1, C18:2 and C18:1-OH acylcarnitines; of particular note, oleyl-L-carnitine (C18:1) and linoleyl-L-carnitine (C18:2) were, on average, 30-40% lower in patients than controls (P < 0.0001). Significant correlations between acylcarnitine concentrations and clinical symptomology were also demonstrated.

CONCLUSIONS: It is proposed that this disturbance in carnitine homeostasis is reflective of a reduction in carnitine palmitoyltransferase-I (CPT-I) activity, possibly a result of the accumulation of omega-6 fatty acids previously observed in this patient population. It is hypothesized that the administration of omega-3 fatty acids in combination with l-carnitine would increase CPT-I activity and improve chronic fatigue syndrome symptomology.

© 2011 The Association for the Publication of the Journal of Internal Medicine.

 

Source: Reuter SE, Evans AM. Long-chain acylcarnitine deficiency in patients with chronic fatigue syndrome. Potential involvement of altered carnitine palmitoyltransferase-I activity. J Intern Med. 2011 Jul;270(1):76-84. doi: 10.1111/j.1365-2796.2010.02341.x. Epub 2011 Jan 19. https://www.ncbi.nlm.nih.gov/pubmed/21205027

 

No evidence for XMRV in German CFS and MS patients with fatigue despite the ability of the virus to infect human blood cells in vitro

Abstract:

BACKGROUND: Xenotropic murine leukemia virus-related virus (XMRV), a novel human retrovirus originally identified in prostate cancer tissues, has recently been associated with chronic fatigue syndrome (CFS), a disabling disease of unknown etiology affecting millions of people worldwide. However, several subsequent studies failed to detect the virus in patients suffering from these illnesses or in healthy subjects. Here we report the results of efforts to detect antibody responses and viral sequences in samples from a cohort of German CFS and relapsing remitting multiple sclerosis (MS) patients with fatigue symptoms.

METHODOLOGY: Blood samples were taken from a cohort of 39 patients fulfilling the Fukuda/CDC criteria (CFS), from 112 patients with an established MS diagnosis and from 40 healthy donors. Fatigue severity in MS patients was assessed using the Fatigue Severity Scale (FSS). Validated Gag- and Env-ELISA assays were used to screen sera for XMRV antibodies. PHA-activated PBMC were cultured for seven days in the presence of IL-2 and DNA isolated from these cultures as well as from co-cultures of PBMC and highly permissive LNCaP cells was analyzed by nested PCR for the presence of the XMRV gag gene. In addition, PBMC cultures were exposed to 22Rv1-derived XMRV to assess infectivity and virus production.

CONCLUSION: None of the screened sera from CFS and MS patients or healthy blood donors tested positive for XMRV specific antibodies and all PBMC (and PBMC plus LNCaP) cultures remained negative for XMRV sequences by nested PCR. These results argue against an association between XMRV infection and CFS and MS in Germany. However, we could confirm that PBMC cultures from healthy donors and from CFS patients can be experimentally infected by XMRV, resulting in the release of low levels of transmittable virus.

 

Source: Hohn O, Strohschein K, Brandt AU, Seeher S, Klein S, Kurth R, Paul F, Meisel C, Scheibenbogen C, Bannert N. No evidence for XMRV in German CFS and MS patients with fatigue despite the ability of the virus to infect human blood cells in vitro. PLoS One. 2010 Dec 22;5(12):e15632. doi: 10.1371/journal.pone.0015632. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3008728/ (Full article)

 

Cognitive impairment in fatigue and sleepiness associated conditions

Abstract:

Although relating to very different concepts, sleepiness and fatigue are often confounded. However, both fatigue-associated conditions such as the chronic fatigue syndrome (CFS) and sleepiness-associated conditions such as the sleep apnea-hypopnea syndrome (SAHS) are associated with cognitive impairment with impaired attention, concentration and memory performances.

Fifteen pure CFS patients, without primary sleep disorders or clinically relevant sleepiness, were compared to 15 untreated SAHS patients, without clinically relevant fatigue, and to 16 healthy controls of similar age. The auditory verbal learning test (AVLT), digit span, digit symbol and finger tapping test (FTT) were used as cognitive and behavioural measures. In addition we assessed daytime EEG spectral power and P300 evoked potentials.

With exception for the digit span, all tests showed lower performances in patient groups. Recall on the AVLT did not differ between the two patient groups, but the digit and symbol spans showed more severe impairment in SAHS patients. Psychomotor performance on the FTT presented with slower hit rates in SAHS than in CFS. EEG theta power was highest in CFS patients. P300 latencies and amplitudes did not differ between groups.

Fatigue- and sleepiness-associated conditions can both present with significant and objective impairment of cognitive functioning and behavioural motor performance. In our sample cognitive impairment and psychomotor performance were worse when associated to sleepiness in SAHS than with fatigue in CFS.

Copyright © 2010 Elsevier Ltd. All rights reserved.

 

Source: Neu D, Kajosch H, Peigneux P, Verbanck P, Linkowski P, Le Bon O. Cognitive impairment in fatigue and sleepiness associated conditions. Psychiatry Res. 2011 Aug 30;189(1):128-34. doi: 10.1016/j.psychres.2010.12.005. Epub 2010 Dec 31. https://www.ncbi.nlm.nih.gov/pubmed/21196050

 

An unbiased metagenomic search for infectious agents using monozygotic twins discordant for chronic fatigue

Abstract:

BACKGROUND: Chronic fatigue syndrome is an idiopathic syndrome widely suspected of having an infectious or immune etiology. We applied an unbiased metagenomic approach to try to identify known or novel infectious agents in the serum of 45 cases with chronic fatigue syndrome or idiopathic chronic fatigue. Controls were the unaffected monozygotic co-twins of cases, and serum samples were obtained at the same place and time.

RESULTS: No novel DNA or RNA viral signatures were confidently identified. Four affected twins and no unaffected twins evidenced viremia with GB virus C (8.9% vs. 0%, p = 0.019), and one affected twin had previously undetected hepatitis C viremia. An excess of GB virus C viremia in cases with chronic fatigue requires confirmation.

CONCLUSIONS: Current, impairing chronic fatigue was not robustly associated with viremia detectable in serum.

 

Source: Sullivan PF, Allander T, Lysholm F, Goh S, Persson B, Jacks A, Evengård B, Pedersen NL, Andersson B. An unbiased metagenomic search for infectious agents using monozygotic twins discordant for chronic fatigue. BMC Microbiol. 2011 Jan 2;11:2. doi: 10.1186/1471-2180-11-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022642/ (Full article)

 

Classifying medication use in clinical research

Abstract:

BACKGROUND: Medication use data are usually collected in clinical research. Yet no standardized method for categorizing these exists, either for sample description or for the study of medication use as a variable.

OBJECTIVE: The present investigation was designed to develop a simple, empirically based classification scheme for medication use categorization.

METHOD: The authors used factor analysis to reduce the number of possible medication groupings. This permitted a pattern of medication usage to emerge that appeared to characterize specific clinical constellations. To illustrate the technique’s potential, the authors applied this classification system to samples where sleep disorders are prominent: chronic fatigue syndrome and sleep apnea.

RESULTS: The authors’ classification approach resulted in 5 factors that appear to cohere in a logical fashion. These were labeled Cardiovascular or Metabolic Syndrome Medication, Symptom Relief Medication, Psychotropic Medication, Preventative Medication, and Hormonal Medication.

CONCLUSIONS: The findings show that medication profile varies according to clinical sample. The medication profile for participants with sleep apnea reflects known comorbid conditions; the medication profile associated with chronic fatigue syndrome appears to reflect the common perception of this condition as a psychogenic disorder.

 

Source: Rizzo D, Creti L, Bailes S, Baltzan M, Grad R, Amsel R, Fichten CS, Libman E. Classifying medication use in clinical research. J Prim Care Community Health. 2011 Jan 1;2(1):26-32. doi: 10.1177/2150131910385843. Epub 2010 Oct 27. https://www.ncbi.nlm.nih.gov/pubmed/23804659

 

Adolescents with severe chronic fatigue syndrome can make a full recovery

Abstract:

The needs of children and adolescents severely affected by chronic fatigue syndrome, myalgic encephalomyelitis (CFS/ME) are currently inadequately addressed in the UK. Sadly, there are few specialists addressing the needs of these patients who are primarily bed-bound, wheelchair users or who can only leave home on an infrequent basis. Uncertainty about what to offer as well of a lack of funding may play a part. Action for Young people with ME (AYME) suggests that at least 350 severely affected children/adolescents are receiving little or inadequate care to help them overcome this debilitating illness. This case report illustrates how recovery can occur with pragmatic rehabilitation combined with a committed compassionate family based approach.

 

Source: Burgess M, Chalder T. Adolescents with severe chronic fatigue syndrome can make a full recovery. BMJ Case Rep. 2011 May 10;2011. pii: bcr0120113716. doi: 10.1136/bcr.01.2011.3716. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091076/ (Full article)