Tag: 2006

Hit-and-run Injury To The Brain: New Evidence On Chronic Fatigue Causation

Press Release: A seven-year tracking study has prompted scientists to suggest that chronic fatigue syndrome could be the result of brain injuries inflicted during the early stages of glandular fever.

Australian researchers have put the suggestion in this week’s Journal of Infectious Diseases, which reveals new findings from the ‘Dubbo Infection Outcomes Study’. Since 1999, a team led by UNSW Professor Andrew Lloyd have been tracking the long-term health of individuals infected with Epstein-Barr virus (EBV), Ross River virus (RRV) or Q fever infection. Their goal is to discover whether the post-infection fatigue syndrome that may affect up to 100,000 Australians is caused by the persistence of EBV, a weakened immune system, psychological vulnerability, or some combination of these.

Glandular fever — sometimes called ‘the kissing disease’ — is caused by Epstein-Barr virus (EBV). Transmitted via saliva, its acute symptoms include fever, sore throat, tiredness, and swollen lymph glands. Most patients recover within several weeks but one in ten young people will suffer prolonged symptoms, marked by fatigue. When these symptoms persist in disabling degree for six months or more, the illness may be diagnosed as chronic fatigue syndrome (CFS).

The researchers followed the course of illness among 39 people diagnosed with acute glandular fever. Eight patients developed a ‘post-infective fatigue syndrome’ lasting six months or longer, while the remaining 31 recovered uneventfully. Detailed studies of the activity of the Epstein-Barr virus in the blood and the immune response against the virus were conducted on blood samples collected from each individual over 12 months.

Commenting on the findings, Professor Lloyd says: “Our findings reveal that neither the virus nor an abnormal immune response explain the post-infective fatigue syndrome. We now suspect it’s more like a hit and run injury to the brain.

“We believe that the parts of the brain that control perception of fatigue and pain get damaged during the acute infection phase of glandular fever. If you’re still sick several weeks after infection, it seems that the symptoms aren’t being driven by the activity of the virus in body, it’s happening in the brain.”

The research team comprising scientists from the University of New South Wales, the University of Sydney and the Queensland Institute of Medical Research plan to test their ‘brain injury’ hypothesis by doing neurological tests on the study participants.

###

About the Dubbo Infection Outcomes Study: this is a major prospective cohort study following individuals from the time of onset of documented infection with Epstein-Barr virus (the cause of glandular fever), Ross River virus (the mosquito-borne infection which causes rash and joint pain) and Q fever (an infection common in meatworkers and those exposed to livestock).

Research Paper:
‘Prolonged illness after infectious mononucleosis is associated with altered immunity but not with increased viral load’, The Journal of Infectious Diseases, vol. 193 (2006), pp 664-671. Authors: Barbara Cameron, Mandvi Bharadwaj, Jacqueline Burrows, Chrysa Fazou, Denis Wakefield, Ian Hickie, Rosemary French, Rajiv Khanna, Andrew Lloyd.

Funding: The Dubbo Infection Outcomes Study is 82 per cent funded by the US Centers for Disease Control. It also receives funding from the National Health and Medical Research Council of Australia.

 

Source: University of New South Wales. “Hit-and-run Injury To The Brain: New Evidence On Chronic Fatigue Causation.” ScienceDaily. ScienceDaily, 1 March 2006. https://www.sciencedaily.com/releases/2006/03/060301092926.htm

 

Research Provides More Evidence That Chronic Fatigue Syndrome Is A Legitimate Medical Condition

Press Release: Researchers at Georgetown University Medical Center have found that chronic fatigue syndrome (CFS) may be rooted in distinct neurological abnormalities that can be medically tested. Although the sample studied was small, this research provides objective, physiological evidence that the controversial disorder can be considered a legitimate medical condition.

Chronic fatigue syndrome defines a range of illnesses including fibromyalgia and Gulf War syndrome, all of which have fatigue as a major symptom. Even among medical professionals, there is a disagreement about the causes, diagnosis and treatment of CFS because so much about the disorder remains unknown. One reason CFS is difficult to diagnose is because it shares symptoms with many other diseases, including multiple sclerosis and lupus. Even when other illnesses are ruled out and a CFS diagnosis is given, there is not a standardized course of treatment and it’s difficult for doctors to measure patient improvement. Estimates are that two to four times as many women as men are diagnosed with CFS.

The Georgetown study, published in the November edition of the BMC Neurology Journal, an online publication, reveals that patients diagnosed with CFS and its family of illnesses have a set of proteins in their spinal cord fluid that were not detected in healthy individuals. These proteins might give insight into the causes of CFS and could someday be used as markers to diagnose patients with the disorder.

“For years, patients with chronic fatigue syndrome have suffered from painful symptoms for which there is no blood test, diagnosable physical condition or any method for doctors to measure improvement,” said James Baraniuk, MD, assistant professor of medicine at Georgetown University Medical Center and first author on the study. “Our research provides initial evidence that chronic fatigue syndrome and its family of illnesses may be legitimate, neurological diseases and that at least part of the pathology involves the central nervous system.”

The disorder is characterized by profound fatigue that is not improved by bed rest and that may get worse with physical or mental activity, according to the Centers for Disease Control and Prevention. Persons with CFS usually function at a lower level of activity than they were capable of before the onset of illness, feeling too tired to perform normal activities or easily exhausted with no apparent reason. Patients also report various nonspecific symptoms, including weakness, muscle pain, impaired memory and/or mental concentration, insomnia and post-exertional fatigue lasting more than 24 hours.

The study looked at 50 individuals suffering from at least two disorders related to CFS, including fibromyalgia and Gulf War syndrome. By examining spinal cord fluid in patients with CFS and in healthy individuals, the researchers found that CFS patients have 16 proteins that healthy individuals do not. Five of these 16 proteins are found in all patients with the illnesses but in none of the controls. The results indicate that those 16 proteins could possibly serve as a “biosignature” for the disease and could someday be used to diagnose CFS.

“Although this is a small study and more research on the subject is necessary, these results indicate it might be possible to develop a simple laboratory test to diagnose these disorders in the future,” Baraniuk said.

Other co-authors on the paper include Begona Casada, PhD, and Hilda Maibach, MS, of Georgetown University Medical Center; Daniel J. Clauw, MD, of the University of Michigan; and Lewis K. Pannell, PhD, of the University of South Carolina; and Sonya Hess, PhD, of the National Institute of Diabetes and Digestive and Kidney Diseases.

 

Source: Georgetown University Medical Center. “Research Provides More Evidence That Chronic Fatigue Syndrome Is A Legitimate Medical Condition.” ScienceDaily. ScienceDaily, 10 January 2006. www.sciencedaily.com/releases/2006/01/060110013424.htm

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

 

Managing chronic fatigue syndrome in U.K. primary care: challenges and opportunities

Abstract:

Calls for the treatment of chronic fatigue syndrome (CFS) in primary care have been based largely on considerations of the availability and accessibility of resources rather than with reference to a firm evidence base. Treatments such as cognitive-behavioural therapy and graded exercise therapy, which have proven effective for CFS in secondary and specialist care settings, have not been adequately tested in primary care. There are several factors that may affect the generalizability of such treatments. Patients seen in primary care may differ from those seen in secondary care, in terms of both illness beliefs and social characteristics, and these factors need to be taken into account when developing and adapting treatments for primary care. While some primary care physicians experience difficulties in the diagnosis of CFS, we argue that early and authoritative diagnosis and the provision of a tangible explanation for patients’ symptoms are likely to be beneficial. Because of the scarcity of qualified specialist therapists, we need to train primary care practitioners to deliver treatments, and we need more research into the feasibility and effectiveness of doing this. Finally, the primary care setting offers opportunities for the guided development of patient self-help approaches.

 

Source: Wearden AJ, Chew-Graham C. Managing chronic fatigue syndrome in U.K. primary care: challenges and opportunities. Chronic Illn. 2006 Jun;2(2):143-53. https://www.ncbi.nlm.nih.gov/pubmed/17175657

 

Erythrocyte oxidative damage in chronic fatigue syndrome

Abstract:

BACKGROUND: It has been hypothesized that a link exists between erythrocyte metabolism (particularly redox metabolism) and erythrocyte shape and that both are related to erythrocyte deformability. The aim of this research is to confirm the results of earlier studies and to investigate a correlation between erythrocyte morphology and erythrocyte oxidative damage in chronic fatigue syndrome (CFS).

METHODS: Reduced glutathione (GSH), malondialdehyde (MDA), methemoglobin (metHb) and 2,3-diphosphoglyceric acid (2,3-DPG) were measured in 31 patients suffering from CFS and 41 healthy control subjects. Scanning electron microscopic studies of the erythrocytes from both groups were also carried out.

RESULTS: There was evidence of oxidative damage in CFS with statistically significant increases in 2,3-DPG (p < 0.05), metHb (p < 0.005) and MDA (p < 0.01). The CFS patients in this study also had significantly more stomatocytes in their blood than the normal subjects (p < 0.005).

CONCLUSIONS: There is a strong likelihood that the increase in erythrocyte antioxidant activity is associated with the presence of stomatocytes. The results of this study provide further evidence for the role of free radicals in the pathogenesis of CFS and a link between erythrocyte metabolism and erythrocyte shape.

 

Source: Richards RS, Wang L, Jelinek H. Erythrocyte oxidative damage in chronic fatigue syndrome. Arch Med Res. 2007 Jan;38(1):94-8. Epub 2006 Nov 3. https://www.ncbi.nlm.nih.gov/pubmed/17174731

 

Low-resolution electromagnetic brain tomography (LORETA) of monozygotic twins discordant for chronic fatigue syndrome

Abstract:

BACKGROUND: Previous work using quantified EEG has suggested that brain activity in individuals with chronic fatigue syndrome (CFS) and normal persons differs. Our objective was to investigate if specific frequency band-pass regions and spatial locations are associated with CFS using low-resolution electromagnetic brain tomography (LORETA).

METHODS: We conducted a co-twin control study of 17 pairs of monozygotic twins where 1 twin met criteria for CFS and the co-twin was healthy. Twins underwent an extensive battery of tests including a structured psychiatric interview and a quantified EEG. Eyes closed EEG frequency-domain analysis was computed and the entire brain volume was compared of the CFS and healthy twins using a multiple comparison procedure.

RESULTS: Compared with their healthy co-twins, twins with CFS differed in current source density. The CFS twins had higher delta in the left uncus and parahippocampal gyrus and higher theta in the cingulate gyrus and right superior frontal gyrus.

CONCLUSIONS: These findings suggest that neurophysiological activity in specific areas of the brain may differentiate individuals with CFS from those in good health. The study corroborates that slowing of the deeper structures of the limbic system is associated with affect. It also supports the neurobiological model that the right forebrain is associated with sympathetic activity and the left forebrain with the effective management of energy. These preliminary findings await replication.

 

Source: Sherlin L, Budzynski T, Kogan Budzynski H, Congedo M, Fischer ME, Buchwald D. Low-resolution electromagnetic brain tomography (LORETA) of monozygotic twins discordant for chronic fatigue syndrome. Neuroimage. 2007 Feb 15;34(4):1438-42. Epub 2006 Dec 13. https://www.ncbi.nlm.nih.gov/pubmed/17169580

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

Abstract:

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.

 

Source: Maes M, Mihaylova I, Leunis JC. Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins. Neuro Endocrinol Lett. 2006 Oct;27(5):615-21. https://www.ncbi.nlm.nih.gov/pubmed/17159817

 

Long-term outcomes of an integrative rehabilitation program on quality of life: a follow-up study

Abstract:

OBJECTIVE: To assess the long-term effects of an integrative rehabilitation program on the overall quality of life of individuals with chronic fatigue syndrome (CFS).

METHODS: This study utilized a within-subjects, repeated measures cohort design. Twenty-three subjects diagnosed with CFS attended eight sessions of an illness-management group followed by 7 months of goal-oriented, individualized counseling that occurred once weekly for 30 min per session. Quality of life was assessed at five time points (baseline, following the group phase, following the one-on-one phase, and 4 and 12 months following program completion).

RESULTS: A within-subjects repeated measures ANOVA revealed significant increases in overall quality of life for up to 1 year following program completion [F(4, 21)=23.5, P<.001].

CONCLUSIONS: Definitive conclusions about program efficacy are limited by design issues. However, findings suggest that the program may have led to improvement in quality of life for up to 1 year following program completion.

 

Source: Taylor RR, Thanawala SG, Shiraishi Y, Schoeny ME. Long-term outcomes of an integrative rehabilitation program on quality of life: a follow-up study. J Psychosom Res. 2006 Dec;61(6):835-9. https://www.ncbi.nlm.nih.gov/pubmed/17141674