Incidence, prognosis, and risk factors for fatigue and chronic fatigue syndrome in adolescents: a prospective community study

Abstract:

OBJECTIVE: The objective of this study was to describe the incidence, prevalence, risk factors, and prognosis of fatigue, chronic fatigue, and chronic fatigue syndrome in 11- to 15-year-olds.

METHODS: A random general population sample (n = 842) of British adolescents and their parents were assessed at baseline and 4 to 6 months later. The main outcomes were fatigue, chronic fatigue, and chronic fatigue syndrome, operationally defined.

RESULTS: The incidence over 4 to 6 months was 30.3% for fatigue, 1.1% for chronic fatigue, and 0.5% for chronic fatigue syndrome. The point prevalence was 34.1% and 38.1% for fatigue, 0.4% and 1.1% for chronic fatigue, and 0.1% and 0.5% for chronic fatigue syndrome at time 1 and time 2, respectively. Of participants who were fatigued at time 1, 53% remained fatigued at time 2. The 3 cases of chronic fatigue and 1 case of chronic fatigue syndrome at time 1 had recovered by time 2. Higher risk for development of chronic fatigue at time 2 was associated with time 1 anxiety or depression, conduct disorder, and maternal distress; in multivariate analysis, baseline anxiety or depression remained a significant predictor of chronic fatigue. Increased risk for development of fatigue at time 2 was associated with time 1 anxiety or depression, conduct disorder, and older age; in multivariate analyses, these factors and female gender all were significant predictors of fatigue.

CONCLUSIONS: The incidence rates for chronic fatigue and chronic fatigue syndrome in this adolescent sample were relatively high, but the prognosis for these conditions was good. This prospective study provides evidence for an association between emotional/behavioral problems and subsequent onset of fatigue/chronic fatigue.

 

Source: Rimes KA, Goodman R, Hotopf M, Wessely S, Meltzer H, Chalder T. Incidence, prognosis, and risk factors for fatigue and chronic fatigue syndrome in adolescents: a prospective community study. Pediatrics. 2007 Mar;119(3):e603-9. https://www.ncbi.nlm.nih.gov/pubmed/17332180

 

Defining the occurrence and influence of alpha-delta sleep in chronic fatigue syndrome

Abstract:

BACKGROUND: Patients with chronic fatigue syndrome (CFS) present a disordered sleep pattern and frequently undergo polysomnography to exclude a primary sleep disorder. Such studies have shown reduced sleep efficiency, a reduction of deep sleep, prolonged sleep initiation, and alpha-wave intrusion during deep sleep. Deregulation of the 2-5A synthetase/RNase L antiviral pathway and a potential acquired channelopathy are also found in a subset of CFS patients and could lead to sleep disturbances. This article compiles a large sleep study database on CFS patients and correlates these data with a limited number of immune parameters as it has been thought that RNase L could be associated with these sleep disturbances.

METHODS: Forty-eight patients who fulfilled 1994 Centers for Disease Control and Prevention criteria for CFS underwent extensive medical evaluation, routine laboratory testing, and a structured psychiatric interview. Subjects then completed a complaint checklist and a two-night polysomnographic investigation. RNase L analysis was performed by gel electrophoresis using a radiolabeled 2′,5′-oligoadenylate trimer. Basic descriptive statistical parameters were calculated.

RESULTS: Patients experienced a prolonged sleep latency, showed a low sleep efficiency index, and had a low percentage of slow wave sleep. The present alpha-delta intrusion correlated with anxiety; no correlations appeared, however, between alpha-delta sleep and immunologic parameters, including RNase L.

CONCLUSIONS: The main findings are 1) validation of sleep latency problems and other sleep disturbances as already suggested by several authors; 2) alpha-delta intrusion seems associated with anxiety; and 3) elevated RNase L did not correlate with alpha-delta sleep.

 

Source: Van Hoof E, De Becker P, Lapp C, Cluydts R, De Meirleir K. Defining the occurrence and influence of alpha-delta sleep in chronic fatigue syndrome. Am J Med Sci. 2007 Feb;333(2):78-84. https://www.ncbi.nlm.nih.gov/pubmed/17301585

 

Fibromylagia, chronic fatigue, and adult attention deficit hyperactivity disorder in the adult: a case study

Abstract:

Adult attention deficit hyperactivity disorder (ADHD) may share common features with fibromyalgia syndrome (FMS) and chronic fatigue syndrome(CFS). In an outpatient psychiatric clinic, a number of adult patients who presented primarily with symptoms of ADHD, predominately inattentive type, also reported unexplained fatigue, widespread musculoskeletal pain or a pre-existing diagnosis of CFS or FMS.

As expected, ADHD pharmacotherapy usually attenuated the core ADHD symptoms of inattention, distractibility, hyperactivity, and impulsivity. Less expected was the observation that some patients also reported amelioration of pain and fatigue symptoms. The utility of ADHD medications in FMS and CFS states may be their innate arousal and enhanced filtering properties.

This model supposes that FMS and CFS are central processing problems rather than peripheral disorders of muscles and joints.

 

Source: Young JL, Redmond JC. Fibromylagia, chronic fatigue, and adult attention deficit hyperactivity disorder in the adult: a case study. Psychopharmacol Bull. 2007;40(1):118-26. https://www.ncbi.nlm.nih.gov/pubmed/17285103

 

An ‘overwhelming illness’: women’s experiences of learning to live with chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

The processes through which people learn to live with CFS/ME are poorly understood and have not been rigorously explored within the literature. Semi-structured interviews were conducted with eight women and analysed using interpretative phenomenological analysis. Participants initially described being ‘overwhelmed’ by CFS/ME. Attempts at seeking help were unsatisfactory and participants described feeling let down and disbelieved.

Participants reacted to this by identifying types of ‘self-help’ and assertively taking more responsibility for their illness and its treatment. Acquiring social support and greater knowledge were key mediating factors in the emergence of control and acceptance. The relevance of the themes to existing research and the implications for clinical practice are considered.

 

Source: Edwards CR, Thompson AR, Blair A. An ‘overwhelming illness’: women’s experiences of learning to live with chronic fatigue syndrome/myalgic encephalomyelitis. J Health Psychol. 2007 Mar;12(2):203-14. https://www.ncbi.nlm.nih.gov/pubmed/17284485

 

Enhanced feedback sensitivity to prednisolone in chronic fatigue syndrome

Abstract:

OBJECTIVE: Enhancement of negative feedback control of the HPA axis in patients with chronic fatigue syndrome (CFS) has been reported using the low dose dexamethasone suppression test. We have developed the use of prednisolone (5mg) as a more physiologically appropriate alternative to dexamethasone in the investigation of mild degrees of glucocorticoid resistance or supersensitivity. The objective of the study was to use this test to look for alterations in negative feedback control of the HPA axis in CFS patients.

METHODS: Fifteen patients with CFS were recruited after fulfilling strict criteria including the absence of comorbid psychiatric diagnosis. They collected urine between 0900 and 1800h and saliva at 0900h pre-prednisolone. At midnight, they took prednisolone (5mg) orally and then collected urine and saliva at the same intervals the following day.

RESULTS: Salivary cortisol was lower in CFS subjects pre-prednisolone than controls. Urinary cortisol metabolites were lower in CFS subjects pre-prednisolone, but did not reach significance. Both measures were significantly lower in CFS subjects post-dose. Mean percentage suppression of both salivary cortisol and urinary cortisol metabolites was significantly higher in CFS compared to controls.

CONCLUSION: There is enhanced sensitivity of the HPA axis to negative feedback in CFS as demonstrated using the prednisolone suppression test. This provides further evidence of alterations in the control of the HPA axis in patients with established CFS.

 

Source: Jerjes WK, Taylor NF, Wood PJ, Cleare AJ. Enhanced feedback sensitivity to prednisolone in chronic fatigue syndrome. Psychoneuroendocrinology. 2007 Feb;32(2):192-8. Epub 2007 Feb 5. https://www.ncbi.nlm.nih.gov/pubmed/17276605

 

Activation of human herpesviruses 6 and 7 in patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Human herpesvirus 6 (HHV-6) and 7 (HHV-7) have been suggested as possible triggering agents for chronic fatigue syndrome(CFS).

OBJECTIVES: To determine the possible association of HHV-6 and HHV-7 infections with CFS.

STUDY DESIGN: The prevalence of latent/persistent and active viral infections by nPCR, characteristic of HHV-6 variants using restriction endonuclease analysis and changes of lymphocyte subsets in peripheral blood by laser flow-cytometry in 17 CFS patients was examined. In addition, 12 patients with unexplained chronic fatigue and 20 blood donors (BD) were studied.

RESULTS: No difference in prevalence of latent/persistent single viral infections between the patients and BD was found but dual infection rate was significantly higher in CFS patients. Active HHV-6 and dual (HHV-6 + HHV-7) infections were detected in CFS patients only and frequency of HHV-7 reactivation was also significantly higher in these patients. HHV-6 variant B was predominant in CFS patients (12/13). The changes of immunological parameters in CFS patients with active dual infection were characterized by significant decrease of CD3+ and CD4+ T cells, significant increase of CD95+ cells and decrease of CD4+/CD8+ ratio.

CONCLUSIONS: HHV-6 and HHV-7 may be involved in the pathogenesis of CFS and reactivation of both viruses may provoke changes in the phenotype of circulating lymphocytes.

 

Source: Chapenko S, Krumina A, Kozireva S, Nora Z, Sultanova A, Viksna L, Murovska M. Activation of human herpesviruses 6 and 7 in patients with chronic fatigue syndrome. J Clin Virol. 2006 Dec;37 Suppl 1:S47-51. https://www.ncbi.nlm.nih.gov/pubmed/17276369

 

Is human herpesvirus-6 a trigger for chronic fatigue syndrome?

Abstract:

Chronic fatigue syndrome (CFS) is an illness currently defined entirely by a combination of non-specific symptoms. Despite this subjective definition, CFS is associated with objective underlying biological abnormalities, particularly involving the nervous system and immune system.

Most studies have found that active infection with human herpesvirus-6 (HHV-6)–a neurotropic, gliotropic and immunotropic virus–is present more often in patients with CFS than in healthy control and disease comparison subjects, yet it is not found in all patients at the time of testing. Moreover, HHV-6 has been associated with many of the neurological and immunological findings in patients with CFS.

Finally, CFS, multiple sclerosis and seizure disorders share some clinical and laboratory features and, like CFS, the latter two disorders also are being associated increasingly with active HHV-6 infection. Therefore, it is plausible that active infection with HHV-6 may trigger and perpetuate CFS in a subset of patients.

 

Source: Komaroff AL. Is human herpesvirus-6 a trigger for chronic fatigue syndrome? J Clin Virol. 2006 Dec;37 Suppl 1:S39-46. https://www.ncbi.nlm.nih.gov/pubmed/17276367

 

Use of valganciclovir in patients with elevated antibody titers against Human Herpesvirus-6 (HHV-6) and Epstein-Barr Virus (EBV) who were experiencing central nervous system dysfunction including long-standing fatigue

Abstract:

BACKGROUND:Twelve patients with long-standing symptoms of central nervous system (CNS) dysfunction were found to have elevated antibody titres to human herpesvirus-6 (HHV-6) and Epstein-Barr virus (EBV). All patients had four or more of the following neurocognitive symptoms: impaired cognitive functioning, slowed processing speed, sleep disturbance, short-term memory deficit, fatigue and symptoms consistent with depression.

OBJECTIVES: We sought to determine whether elevated antibodies to EBV and HHV-6 indicated chronic viral activation in patients with CNS dysfunction and if their symptoms could be improved by suppressing viral activity with oral valganciclovir.

STUDY DESIGN: Patients with high IgG antibody titers against HHV-6 and EBV who were suffering from central nervous system dysfunction and debilitating fatigue for more than one year (median 3 years, range 1-8 years) were treated with 6 months of valganciclovir in an open label study.

RESULTS: Nine out of 12 (75%) patients experienced near resolution of their symptoms, allowing them all to return to the workforce or full time activites. In the nine patients with a symptomatic response to treatment, EBV VCA IgG titers dropped from 1:2560 to 1:640 (p = 0.008) and HHV-6 IgG titers dropped from a median value of 1:1280 to 1:320 (p = 0.271). Clinically significant hematological toxicity or serious adverse events were not observed among the 12 patients.

CONCLUSION: These preliminary clinical and laboratory observations merit additional studies to establish whether this clinical response is mediated by an antiviral effect of the drug, indirectly via immunomodulation or by placebo effect.

 

Source: Kogelnik AM, Loomis K, Hoegh-Petersen M, Rosso F, Hischier C, Montoya JG. Use of valganciclovir in patients with elevated antibody titers against Human Herpesvirus-6 (HHV-6) and Epstein-Barr Virus (EBV) who were experiencing central nervous system dysfunction including long-standing fatigue. J Clin Virol. 2006 Dec;37 Suppl 1:S33-8. https://www.ncbi.nlm.nih.gov/pubmed/17276366

 

Continuous measurement of BRSI in chronic fatigue syndrome

Abstract:

This paper discusses the development of a system to measure continuous cardiac baroreceptor measurement during a 45-minute 70-degree head-up tilt (HUT) of five groups of subjects suffering the following: chronic fatigue syndrome (CFS), CFS with fibromyalgia (CFS-FM), CFS with postural orthostatic tachycardia syndrome (CFS-POTS), controls with POTS (CON-POTS), and controls (CON). The duration of the test was 56-minutes, which included a five-minute supine baseline, a 45-minute HUT and a six-minute recovery period. The system was developed in LabView, and can provide a comparative time analyses of weighted BRSI averages. Baroreflex effectiveness index (BEI) was also investigated over the course of lags 0, 1 and 2 as well as an assessment of overall BEI performance between groups.

 

Source: Donnelly DL, Rockland RH, Reisman SS, Quigley KS. Continuous measurement of BRSI in chronic fatigue syndrome. Conf Proc IEEE Eng Med Biol Soc. 2004;2:906-8. https://www.ncbi.nlm.nih.gov/pubmed/17271825

 

Hypocapnia is a biological marker for orthostatic intolerance in some patients with chronic fatigue syndrome

Abstract:

CONTEXT: Patients with chronic fatigue syndrome and those with orthostatic intolerance share many symptoms, yet questions exist as to whether CFS patients have physiological evidence of orthostatic intolerance.

OBJECTIVE: To determine if some CFS patients have increased rates of orthostatic hypotension, hypertension, tachycardia, or hypocapnia relative to age-matched controls.

DESIGN: Assess blood pressure, heart rate, respiratory rate, end tidal CO2 and visual analog scales for orthostatic symptoms when supine and when standing for 8 minutes without moving legs.

SETTING: Referral practice and research center.

PARTICIPANTS: 60 women and 15 men with CFS and 36 women and 4 men serving as age matched controls with analyses confined to 62 patients and 35 controls showing either normal orthostatic testing or a physiological abnormal test.

MAIN OUTCOME MEASURES: Orthostatic tachycardia; orthostatic hypotension; orthostatic hypertension; orthostatic hypocapnia or combinations thereof.

RESULTS: CFS patients had higher rates of abnormal tests than controls (53% vs 20%, p < .002), but rates of orthostatic tachycardia, orthostatic hypotension, and orthostatic hypertension did not differ significantly between patients and controls (11.3% vs 5.7%, 6.5% vs 2.9%, 19.4% vs 11.4%, respectively). In contrast, rates of orthostatic hypocapnia were significantly higher in CFS than in controls (20.6% vs 2.9%, p < .02). This CFS group reported significantly more feelings of illness and shortness of breath than either controls or CFS patients with normal physiological tests.

CONCLUSION: A substantial number of CFS patients have orthostatic intolerance in the form of orthostatic hypocapnia. This allows subgrouping of patients with CFS and thus reduces patient pool heterogeneity engendered by use of a clinical case definition.

 

Source: Natelson BH, Intriligator R, Cherniack NS, Chandler HK, Stewart JM. Hypocapnia is a biological marker for orthostatic intolerance in some patients with chronic fatigue syndrome. Dyn Med. 2007 Jan 30;6:2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1796865/ (Full article)