CHRONIC FATIGUE SYNDROME BEGINNING SUDDENLY OCCURS SEASONALLY OVER THE YEAR

The fact that many patients with chronic fatigue syndrome (CFS) have an infectiouslike sudden onset to their illness has led to the hypothesis that CFS is a medical illness. If CFS were, on the other hand, a psychiatric disorder related to symptom amplification, one would expect illness onset to occur randomly over the calendar year. This study tested that hypothesis with 69 CFS patients whose illness was on the more severe side of the illness spectrum; all patients reported sudden illness onset with the full syndrome of sore throat, fatigue/malaise, and diffuse achiness developing over no longer than a 2-day period. Date of illness onset was distinctly nonrandom. It peaked from November through January and was at its lowest from April through May. These data support the hypothesis that an infectious illness can trigger the onset of CFS. (Chronobiology International, 17(1), 95–99, 2000).

Chronic fatigue syndrome (CFS) is a medically unexplained illness characterized by fatigue, pain, and cognitive complaints. Because many of the symptoms of CFS overlap with those of depression, some argue that CFS is a somatic manifestation of depression or a somatoform disorder. Komaroff (1988) has suggested that, because CFS patients develop their illness suddenly with an infectiouslike presentation, this supports an underlying medical etiology to the illness. If CFS were indeed triggered by an infectious illness, one would expect to find the dates of sudden illness onset to occur more often in months when viral infections are common. If CFS were a somatoform disorder, one would expect a random distribution of dates of illness onset across the calendar year. Since our center has a large number of CFS patients who report a sudden infectiouslike illness onset, the purpose of this paper was to determine if the dates of illness onset occurred randomly or nonrandomly across the calendar year.     

Chronic fatigue syndrome beginning suddenly occurs seasonally over the year

The fact that many patients with chronic fatigue syndrome (CFS) have an infectiouslike sudden onset to their illness has led to the hypothesis that CFS is a medical illness. If CFS were, on the other hand, a psychiatric disorder related to symptom amplification, one would expect illness onset to occur randomly over the calendar year. This study tested that hypothesis with 69 CFS patients whose illness was on the more severe side of the illness spectrum; all patients reported sudden illness onset with the full syndrome of sore throat, fatigue/malaise, and diffuse achiness developing over no longer than a 2-day period. Date of illness onset was distinctly nonrandom. It peaked from November through January and was at its lowest from April through May. These data support the hypothesis that an infectious illness can trigger the onset of CFS. (Chronobiology International, 17(1), 95-99, 2000).

Chronic fatigue syndrome (CFS) is a medically unexplained illness characterized by fatigue, pain, and cognitive complaints. Because many of the symptoms of CFS overlap with those of depression, some argue that CFS is a somatic manifestation of depression or a somatoform disorder. Komaroff (1988) has suggested that, because CFS patients develop their illness suddenly with an infectiouslike presentation, this supports an underlying medical etiology to the illness. If CFS were indeed triggered by an infectious illness, one would expect to find the dates of sudden illness onset to occur more often in months when viral infections are common. If CFS were a somatoform disorder, one would expect a random distribution of dates of illness onset across the calendar year. Since our center has a large number of CFS patients who report a sudden infectiouslike illness onset, the purpose of this paper was to determine if the dates of illness onset occurred randomly or nonrandomly across the calendar year.     

Childhood predictors of self reported chronic fatigue syndrome/myalgic encephalomyelitis in adults: national birth cohort study

Objective To study childhood risk factors for chronic fatigue syndrome in adult life.Design Examination of data from the 1970 British birth cohort.Participants 16 567 babies born 5-11 April 1970, followed up at 5, 10, 16, and 29-30 years.Main outcome measures Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) identified by self report at age 30 years. Data from childhood from questionnaires given to parents and teachers. Maternal mental health assessed with the malaise inventory.Results 93 (0.8%, 95% confidence interval 0.7 to 1.0) of 11 261 participants reported ever having CFS/ME, and 48 (0.4%, 0.3 to 0.6) had the condition currently. Higher risk of CFS/ME was associated with having a limiting longstanding condition in childhood (odds ratio 2.3, 1.4 to 3.9), female sex (2.3, 1.4 to 2.6), and high social class in childhood (2.2, 1.4 to 3.5). Higher levels of exercise in childhood were associated with lower risk (0.5, 0.2 to 0.9). Maternal psychological disorder, psychological problems in childhood, birth weight, birth order, atopy, obesity, school absence, academic ability, and parental illness were not associated with risk of CFS/ME.Conclusions We identified no association between maternal or child psychological distress, academic ability, parental illness, atopy, or birth order and increasing risk of lifetime CFS/ME. Sedentary behaviour increased the risk.     

A community-based study of seasonal variation in the onset of chronic fatigue syndrome and idiopathic chronic fatigue

One proposed hypothesis regarding the etiology of chronic fatigue syndrome (CFS) is that there is a subgroup of patients in which symptom onset is precipitated by a viral infection. If this is indeed true, then one would anticipate a greater incidence of the emergence of CFS symptoms during months when viral infections occur with the greatest frequency. The current community-based epidemiology study examined the month of symptom onset for 31 patients with CFS and 44 others with idiopathic chronic fatigue (ICF). It was determined that the distribution of the month of illness onset for the CFS and ICF groups was nonrandom, with greater numbers of participants than expected reporting an onset of CFS and ICF during January. (Chronobiology International, 18(2), 315-319, 2001)     

In chronic fatigue syndrome, the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activation

There is now evidence that major depression is accompanied by decreased levels of omega3 poly-unsaturated fatty acids (PUFA), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). There is a strong comorbidity between major depression and chronic fatigue syndrome (CFS). The present study has been carried out in order to examine PUFA levels in CFS. In twenty-two CFS patients and 12 normal controls we measured serum PUFA levels using gas chromatography and mass spectrometry. We found that CFS was accompanied by increased levels of omega6 PUFAs, i.e. linoleic acid and arachidonic acid (AA), and mono-unsaturated fatty acids (MUFAs), i.e. oleic acid. The EPA/AA and total omega3/omega6 ratios were significantly lower in CFS patients than in normal controls. The omega3/omega6 ratio was significantly and negatively correlated to the severity of illness and some items of the FibroFatigue scale, i.e. aches and pain, fatigue and failing memory. The severity of illness was significantly and positively correlated to linoleic and arachidonic acid, oleic acid, omega9 fatty acids and one of the saturated fatty acids, i.e. palmitic acid. In CFS subjects, we found significant positive correlations between the omega3/omega6 ratio and lowered serum zinc levels and the lowered mitogen-stimulated CD69 expression on CD3+, CD3+ CD4+, and CD3+ CD8+ T cells, which indicate defects in early T cell activation. The results of this study show that a decreased availability of omega3 PUFAs plays a role in the pathophysiology of CFS and is related to the immune pathophysiology of CFS. The results suggest that patients with CFS should respond favourably to treatment with--amongst other things--omega3 PUFAs, such as EPA and DHA.     

Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome

Background

In October 2009 it was reported that 68 of 101 patients with chronic fatigue syndrome (CFS) in the US were infected with a novel gamma retrovirus, xenotropic murine leukaemia virus-related virus (XMRV), a virus previously linked to prostate cancer. This finding, if confirmed, would have a profound effect on the understanding and treatment of an incapacitating disease affecting millions worldwide. We have investigated CFS sufferers in the UK to determine if they are carriers of XMRV.

Methodology

Patients in our CFS cohort had undergone medical screening to exclude detectable organic illness and met the CDC criteria for CFS. DNA extracted from blood samples of 186 CFS patients were screened for XMRV provirus and for the closely related murine leukaemia virus by nested PCR using specific oligonucleotide primers. To control for the integrity of the DNA, the cellular beta-globin gene was amplified. Negative controls (water) and a positive control (XMRV infectious molecular clone DNA) were included. While the beta-globin gene was amplified in all 186 samples, neither XMRV nor MLV sequences were detected.

Conclusion

XMRV or MLV sequences were not amplified from DNA originating from CFS patients in the UK. Although we found no evidence that XMRV is associated with CFS in the UK, this may be a result of population differences between North America and Europe regarding the general prevalence of XMRV infection, and might also explain the fact that two US groups found XMRV in prostate cancer tissue, while two European studies did not.     

The use of transfer factors in chronic fatigue syndrome: prospects and problems

Chronic fatigue syndrome (CFS) is a heterogeneous disorder characterized by severe prolonged unexplained fatigue and a variety of associated symptoms such as arthralgias, myalgias, cognitive dysfunction, and severe sleep disturbances. Many patients initially present with an acute onset of apparent infectious origin with either an upper respiratory or gastrointestinal illness, fever, chills, tender lymphadenopathy, and malaise suggestive of a flu-like illness. In some cases, specific viral infections can be identified at the outset, particularly herpes viruses such as Epstein-Barr virus (EBV), human herpes virus-6 (HHV-6), and cytomegalovirus (CMV). Transfer factors (TF) with specific activity against these herpes viruses has been documented. With some studies suggesting that persistent viral activity may play a role in perpetuation of CFS symptoms, there appears to be a rationale for the use of TF in patients with CFS and recent reports have suggested that transfer factor may play a beneficial role in this disorder. This report focuses on the heterogeneity of CFS, the necessity for randomized coded studies, the importance of patient selection and sub-classification in clinical trials, and the need to utilize specific end-points for determining efficacy of treatment.     

Are ME/CFS Patient Organizations “Militant”?

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a contested illness category. This paper investigates the common claim that patients with ME/CFS—and by extension, ME/CFS patient organizations (POs)—exhibit “militant” social and political tendencies. The paper opens with a history of the protracted scientific disagreement over ME/CFS. We observe that ME/CFS POs, medical doctors, and medical researchers exhibit clear differences in opinion over how to conceptualize this illness. However, we identify a common trope in the discourse over ME/CFS: the claim of “militant” patient activism. Scrutinizing this charge, we find no compelling evidence that the vast majority of patients with ME/CFS, or the POs representing them, have adopted any such militant political policies or behaviours. Instead, we observe key strategic similarities between ME/CFS POs in the United Kingdom and the AIDs activist organizations of the mid-1980s in the United States which sought to engage scientists using the platform of public activism and via scientific publications. Finally, we explore the contours of disagreement between POs and the medical community by drawing on the concept of epistemic injustice. We find that widespread negative stereotyping of patients and the marginalization and exclusion of patient voices by medical authorities provides a better explanation for expressions of frustration among patients with ME/CFS.     

Characterization of a prospective human model for study of the reproductive hormone responses to major illness

With critical illness, serum testosterone levels fall markedly, whereas estrogen levels rise. Although animal studies suggest adaptive advantages, no prospective model has been available for studies in humans. We hypothesized that coronary artery bypass graft (CABG) surgery would provide such a model by eliciting the same reproductive hormone and other endocrine responses as reported with major nonsurgical illnesses. We further hypothesized that those responses would occur consistently in all CABG patients with predictable time courses, providing reliable windows for prospective studies. In 17 men undergoing CABG, serum levels of reproductive hormones, cortisol, thyroid hormones, and IGF-I were measured before and for up to 5 wk after surgery. Changes in serum levels of reproductive and other hormones were similar to those reported in nonsurgical critically ill patients. Time course for onset, duration, and recovery of reproductive hormone changes were consistent among all patients. A window for studying the testosterone and estrogen responses was established as the first 5 days following CABG. Practical use of this model was demonstrated by evaluating, in another seven men, changes in gonadotroph responsiveness to GnRH following CABG. Finally, to determine whether our findings in CABG could be extended to other surgeries, we demonstrated similar endocrine responses in 12 men following abdominal aortic aneurysm resection. We conclude that patients undergoing CABG surgery provide a useful human model for the prospective evaluation of the reproductive axis responses to acute illness. Other major surgeries are likely to also be suitable for these studies.     

Mechanisms underlying eating-drinking transitions in rats

McFarland (1969) suggested two mechanisms whereby a switch could occur from one activity to another: ‘competition’, which he depicted as a gradual increase in the causal-factor strength (CFS) of activity 2, and ‘disinhibition’, which he depticted as a sudden decrease in the CFS of activity 1. We postulate two further mechanisms: ‘satiation’, depicted as a gradual decrease in the CFS of activity 1, and ‘inhibition’, depicted as a sudden increase in the CFS of activity 2. We suggest that disinhibition may be a less common mechanism of behavioural switching than is usually supposed, and describe three experiments suggesting that eat/drink and drink/eat switches in the rat occur by competition and/or satiation rather than by disinhibition and/or inhibition. In experiment 1, varying degrees of water deprivation were found to affect the timing of eat/drink switches in food-deprived rats; in experiment 2, varying rates of food availability were found to affect the timing of drink/eat switches in water-deprived rats; in experiment 3, drink/eat switches were delayed by allowing rats to ‘drink’ air instead of water.     

Are all born equal? Incidence of febrile convulsions by seasons of birth.

To test whether the seasons of birth had an effect on subsequent experience of illness, details were obtained of all Sheffield children born between 1973 and 1977 who were admitted to hospital before their second birthday with a first febrile convulsion. Analysis by date of birth in consecutive 28-day cohorts showed that the incidence of febrile convulsions ranged from 2.5 per thousand live births to 30.2 per thousand in different "month" cohorts. Statistically significant variations were noted in the incidence rates in relation to season and year of birth. The implication is that even large scale epidemiological studies which have been confined to children born in a particular week or month may not be representative of the whole child population.     

Evaluation of Resting State Networks in Patients with Gliomas: Connectivity Changes in the Unaffected Side and Its Relation to Cognitive Function

In this study, we investigated changes in resting state networks (RSNs) in patients with gliomas located in the left hemisphere and its relation to cognitive function. We hypothesized that long distance connection, especially between hemispheres, would be affected by the presence of the tumor. We further hypothesized that these changes would correlate with, or reflect cognitive changes observed in patients with gliomas. Resting state functional MRI datasets from 12 patients and 12 healthy controls were used in the analysis. The tumor’s effect on three well-known RSNs including the default mode network (DMN), executive control network (ECN), and salience network (SN) identified using independent component analysis were investigated using dual regression analysis. Scores of neuropsychometric testing (WAIS-III and WMS-R) were also compared. Compared to the healthy control group, the patient group showed significant decrease in functional connectivity in the right angular gyrus/inferior parietal lobe of the ventral DMN and in the dorsolateral prefrontal cortex of the left ECN, whereas a significant increase in connectivity in the right ECN was observed in the right parietal lobe. Changes in connectivity in the right ECN correlated with spatial memory, while that on the left ECN correlated with attention. Connectivity changes in the ventral DMN correlated with attention, working memory, full IQ, and verbal IQ measures. Although the tumors were localized in the left side of the brain, changes in connectivity were observed in the contralateral side. Moreover, these changes correlated with some aspects of cognitive function indicating that patients with gliomas may undergo cognitive changes even in the absence of or before the onset of major symptoms. Evaluation of resting state networks could be helpful in advancing our hodological understanding of brain function in glioma cases.     

Towards Improving Point-of-Care Diagnosis of Non-malaria Febrile Illness: A Metabolomics Approach

IntroductionNon-malaria febrile illnesses such as bacterial bloodstream infections (BSI) are a leading cause of disease and mortality in the tropics. However, there are no reliable, simple diagnostic tests for identifying BSI or other severe non-malaria febrile illnesses. We hypothesized that different infectious agents responsible for severe febrile illness would impact on the host metabololome in different ways, and investigated the potential of plasma metabolites for diagnosis of non-malaria febrile illness.MethodologyWe conducted a comprehensive mass-spectrometry based metabolomics analysis of the plasma of 61 children with severe febrile illness from a malaria-endemic rural African setting. Metabolite features characteristic for non-malaria febrile illness, BSI, severe anemia and poor clinical outcome were identified by receiver operating curve analysis.ConclusionsThis study demonstrates the potential use of plasma metabolites to identify causality in children with severe febrile illness in malaria-endemic settings.     

WPA guidance on the protection and promotion of mental health in children of persons with severe mental disorders

This guidance details the needs of children, and the qualities of parenting that meet those needs. Parental mental disorders can damage the foetus during pregnancy through the action of drugs, prescribed or abused. Pregnancy and the puerperium can exacerbate or initiate mental illness in susceptible women. After their birth, the children may suffer from the social disadvantage associated with severe mental illness. The parents (depending on the disorder, its severity and its persistence) may have intermittent or prolonged difficulties with parenting, which may sometimes result in childhood psychological disturbance or child maltreatment. This guidance considers ways of preventing, minimizing and remedying these effects. Our recommendations include: education of psychiatrists and related professions about the effect of parental mental illness on children; revision of psychiatric training to increase awareness of patients as caregivers, and to incorporate relevant assessment and intervention into their treatment and rehabilitation; the optimum use of pharmacological treatment during pregnancy; pre-birth planning when women with severe mental illness become pregnant; development of specialist services for pregnant and puerperal women, with assessment of their efficacy; community support for parenting by mothers and fathers with severe mental disorders; standards of good practice for the management of child maltreatment when parents suffer from mental illness; the importance of multi-disciplinary teamwork when helping these families, supporting their children and ensuring child protection; the development of child and adolescent mental health services worldwide.     

Functioning in individuals with chronic fatigue syndrome: increased impairment with co-occurring multiple chemical sensitivity and fibromyalgia

Background

Chronic fatigue syndrome (CFS), multiple chemical sensitivity (MCS), and fibromyalgia (FM) commonly co-occur. Some propose that CFS, MCS, and FM are manifestations of the same illness based on high rates of co-occurrence and overlapping diagnostic criteria. This study seeks to differentiate these diagnoses by comparing individuals with one or more illness on functioning, psychiatric comorbidity, coping style, and in vivo physical measures.

Methods

Participants included 114 men and women who met criteria for CFS. FM was diagnosed during a physical examination, and MCS was assessed using a questionnaire. Participants were divided into four groups: CFS alone, CFS-MCS, CFS-FM, and CFS-MCS-FM. Self-report measures, a psychiatric interview, and in vivo physical measures were given.

Results

43.9% met criteria for CFS alone, 23.7% met criteria for CFS-MCS, 15.8% met criteria for CFS-FM, and 16.7% met criteria for CFS-MCS-FM. The CFS-MCS-FM group was more disabled than the CFS alone group on measures of physical functioning, general health, and bodily pain. In vivo measures did not differ, but the CFS-MCS-FM group rated exertion higher than the CFS alone group.

Conclusion

Individuals with CFS alone were the highest functioning group across several domains, such as disability, depression, and severity of symptoms. Participants with three diagnoses experienced the greatest amount of disability. While substantial co-occurrence of these illnesses was found, this study provides evidence that having more than one illness exacerbates one's disability beyond CFS alone.

     

Mother-child separation: a study in a remote health care setting.

The literature indicates that the birth of a sibling and the consequent temporary separation from the mother is usually a stressful experience for a child. It was hypothesized that this stress would result in an increased number of visits by the child to health care facilities because of new health problems. In a controlled study of 89 matched pairs of Indian families in a remote region of northwestern Ontario this hypothesis was not supported. During the intervals studied - the anticipatory period before delivery, the separation itself and the period immediately following the mother''s return home - the number of diagnoses of new medical problems was significantly less for the children who were separated from their mothers for the birth of a sibling. As well, the number of diagnoses of new medical problems in the children separated form their mothers decreased over the three intervals. The fathers'' reluctance to seek health care probably played a major role in this decrease.     

Japanese Patients with Chronic Fatigue Syndrome Are Negative for Known Retrovirus Infections

Although chronic fatigue syndrome (CFS) is known to be the syndrome that begins with an acute flu-like illness that may be due to the exposure to an infectious agent, there has been no convincing evidence on the causative agents. Recently, human T-lymphotropic virus type II (HTLV-II)-like virus has been reported to be associated with the CFS by using HTLV Western blot analysis and polymerase chain reaction. However, some investigators could not detect HTLV-II by indirect immunofluorescence analysis. Lately, CFS patients have been reported in Japan. We detected all 30 tested patients with CFS were seronegative for HTLV-II, HTLV-I and HIV by specific peptide ELISA and Western blot. Further, PCR analysis was negative for HTLV-II and retrovirus was not detected by coculture method with patients' PBMC. Thus, known human retrovirus infections do not cause a CFS in Japan.     

Is there a synergistic effect between steady-state exercise and water acidification in carp?

Carp ( Cyprinus carpio ) fitted with arterial catheters were trained to swim in a swim tunnel. While constantly swimming at two body lengths per second, they were subjected to gradual water acidification (from pH 7–6 to 40 in 4 h), and monitored subsequently over 24 h. It was hypothesized that exercise would expose the gills to a larger extent and that conseq uently the effect of water acidification would be greater in exercising than in resting carp. In contrast to our earlier study with resting carp we found a constant dedine of plasma pH, and of plasma Na⁺ and Cl concentration, indicating ionoregulatory failure. While plasma catecholamincs remained at control levels, the plasma cortisol showed a three- to four-fold increase over the first 7 h. This was followed by a slow decline. We conclude that there is a synergistic effect between moderate exercise and gradual water acidification.     

Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins

There is now some evidence that chronic fatigue syndrome (CFS) is accompanied by signs of oxidative stress and by a decreased antioxidant status. The aim of the present study was to examine whether CFS is accompanied by an immune response to neoepitopes of a variety of modified lipids and proteins indicating damage caused by oxidative and nitrosative stress. Toward this end we examined serum antibodies to fatty acids (oleic, palmitic and myristic acid), by-products of lipid peroxidation, i.e. azelaic acid and malondialdehyde (MDA), acetylcholine, S-farnesyl-L-cysteine, and N-oxide modified amino-acids in 14 patients with CFS, 14 subjects with partial CFS and 11 normal controls. We found that the prevalences and mean values for the serum IgM levels directed against oleic, palmitic and myristic acid, MDA, azelaic acid, S-farnesyl-L-cysteine, and the N-oxide derivates, nitro-tyrosine, nitro-phenylalanine, nitro-arginine, nitro-tryptophan, and nitro-cysteinyl were significantly greater in CFS patients than in normal controls, whereas patients with partial CFS took up an intermediate position. There were significant and positive correlations between the serum IgM levels directed against fatty acids, MDA and azelaic acid and the above N-oxide-derivates and the severity of illness (as measured by the FibroFatigue scale) and symptoms, such as aches and pain, muscular tension and fatigue. The results show that CFS is characterized by an IgM-related immune response directed against disrupted lipid membrane components, by-products of lipid peroxidation, S-farnesyl-L-cysteine, and NO-modified amino-acids, which are normally not detected by the immune system but due to oxidative and nitrosative damage have become immunogenic.