Persistence of enterovirus RNA in muscle biopsy samples suggests that some cases of chronic fatigue syndrome result from a previous, inflammatory viral myopathy

Abstract:

Molecular hybridization using an enterovirus group specific probe detected virus RNA in muscle biopsy samples from 25 of 96 cases of inflammatory muscle disease and similarly from 41 of 158 cases of postviral fatigue syndrome (PFS).

Enterovirus RNA was detected in only two of 152 samples of control muscle. The inflammatory myopathy group comprised patients with polymyositis (PM), juvenile dermatomyositis (JDM) or adult dermatomyositis (DM), and all showed the presence of an inflammatory infiltrate and fiber necrosis on histological examination of a muscle biopsy sample.

In contrast, muscle samples from the PFS group were histologically normal except for non-specific changes such as occasional single fiber atrophy. By analogy with enteroviral myocarditis, which can progress to a post-inflammatory disease with persistence of virus in myocardium and disposes to the rapid development of dilated cardiomyopathy, we propose that PFS syndrome may be a sequela of a previous inflammatory viral myopathy.

 

Source: Bowles NE, Bayston TA, Zhang HY, Doyle D, Lane RJ, Cunningham L, Archard LC. Persistence of enterovirus RNA in muscle biopsy samples suggests that some cases of chronic fatigue syndrome result from a previous, inflammatory viral myopathy. J Med. 1993;24(2-3):145-60. http://www.ncbi.nlm.nih.gov/pubmed/8409778

 

Investigation of retroviral involvement in chronic fatigue syndrome

Abstract:

Within the last few years significant efforts have been made to identify objective reliable diagnostic markers from individuals with chronic fatigue syndrome (CFS).

We report the absence of a previously described retroviral marker (HTLV-II gag) in a blinded study of CFS cases. Even with excellent reproducible sensitivities, this marker failed in repeated attempts to distinguish cases from controls. In addition, four other retroviruses (simian T cell leukaemia virus, human spumavirus, bovine leukaemia virus and simian retrovirus) were examined for their presence in these CFS cases and found to be absent.

Our findings suggest that these agents, at least as markers, are non-distinguishing for CFS and that other factors may be confounding the resolution of an aetiology to this syndrome.

 

Source: Folks TM, Heneine W, Khan A, Woods T, Chapman L, Schonberger L. Investigation of retroviral involvement in chronic fatigue syndrome. Ciba Found Symp. 1993;173:160-6; discussion 166-75. http://www.ncbi.nlm.nih.gov/pubmed/8387909

 

Enteroviruses and postviral fatigue syndrome

Abstract:

Postviral fatigue syndrome (PFS) occurs both in epidemics and sporadically. Many of the original epidemics were related to poliomyelitis outbreaks which either preceded or followed them.

The core clinical symptoms are always the same: severe fatigue made worse by exercise, myalgia, night sweats, atypical depression and excessive sleep. The other common symptoms include dysequilibrium disorders and irritable bowel syndrome.

We have detected enteroviral genome sequences in muscle biopsies from cases of PFS, using specific enteroviral oligonucleotide primers in the polymerase chain reaction (PCR). In addition, whole virus particles can be demonstrated in PCR-positive muscle, using solid-phase immuno-electron microscopy.

An increase in the number and size of muscle mitochondria was found in 70% of PFS cases, suggesting an abnormality in metabolic function. Evidence of hypothalamic dysfunction was present, particularly involving 5-hydroxytryptamine metabolism.

A putative model of PFS, based on persistent enteroviral infection in laboratory mice, revealed resolving inflammatory lesions in muscle with, however, a marked increase in the production of certain cytokines in the brain. This model may help to explain the pathogenesis of PFS.

 

Source: Behan PO, Behan WM, Gow JW, Cavanagh H, Gillespie S. Ciba Found Symp. 1993;173:146-54; discussion 154-9. http://www.ncbi.nlm.nih.gov/pubmed/8387908

 

Studies of herpesvirus infection in chronic fatigue syndrome

Abstract:

The relationship of herpesviruses to chronic fatigue syndrome has received considerable attention over the past decade. Data suggesting an association fall into three major categories.

First, among acute precipitants of the syndrome are primary infections with some herpesviruses, most notably Epstein-Barr virus and cytomegalovirus.

Second, a series of studies have detailed elevations of antibodies to most herpesviruses in selected chronic fatigue syndrome populations, with Epstein-Barr virus and human herpes type 6 being the objects of most scrutiny.

Third, one recent study reported a greater ease of recovery of human herpes virus type 6 from chronic fatigue syndrome patients. This review article critically examines the cumulative data regarding an association between one or more herpesviruses and the chronic fatigue syndrome in the context of the known biology and epidemiology of these agents.

In view of these, and additional considerations regarding study methodologies, the conclusion is drawn that herpesviruses are not dominant causes of the chronic fatigue syndrome and may not even be necessary to the perpetuation of the illness, but it is premature to dismiss entirely this latter possibility.

 

Source: Straus SE. Studies of herpesvirus infection in chronic fatigue syndrome. Ciba Found Symp. 1993;173:132-9; discussion 139-45. http://www.ncbi.nlm.nih.gov/pubmed/8387907

 

Japanese patients with chronic fatigue syndrome are negative for known retrovirus infections

Abstract:

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.

 

Source: Honda M, Kitamura K, Nakasone T, Fukushima Y, Matsuda S, Nishioka K, Matsuda J, Hashimoto N, Yamazaki S. Japanese patients with chronic fatigue syndrome are negative for known retrovirus infections. Microbiol Immunol. 1993;37(10):779-84. http://www.ncbi.nlm.nih.gov/pubmed/7507200

 

Search for retrovirus in the chronic fatigue syndrome

Abstract:

AIM: To examine peripheral blood and skeletal muscle from patients with chronic fatigue syndrome for exogenous retrovirus.

METHODS: Blood samples from 30 patients and muscle biopsy specimens of 15 patients were examined for retroviral sequences by DNA extraction, polymerase chain reaction (PCR), and Southern blotting hybridisation. Sera were examined for human foamy virus by western immunoblotting and indirect immunofluorescence techniques.

RESULTS: No differences between the patient and control populations was found for any of the PCR primer sets used (gag, pol, env, and tax regions of HTLV I/II). An endogenous gag band was observed in both the patient and control groups. All sera were negative for antibody to human foamy virus.

CONCLUSION: The results indicate that there is no evidence of retroviral involvement in the chronic fatigue syndrome.

 

Source: Gow JW, Simpson K, Schliephake A, Behan WM, Morrison LJ, Cavanagh H, Rethwilm A, Behan PO. Search for retrovirus in the chronic fatigue syndrome. J Clin Pathol. 1992 Dec;45(12):1058-61. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC494996/ (Full article)

 

Human herpesvirus 7 is a T-lymphotropic virus and is related to, but significantly different from, human herpesvirus 6 and human cytomegalovirus

Abstract:

An independent strain (JI) of human herpesvirus 7 (HHV-7) was isolated from a patient with chronic fatigue syndrome (CFS). No significant association could be established by seroepidemiology between HHV-7 and CFS.

HHV-7 is a T-lymphotropic virus, infecting CD4+ and CD8+ primary lymphocytes. HHV-7 can also infect SUP-T1, an immature T-cell line, with variable success. Southern blot analysis with DNA probes scanning 58.8% of the human herpesvirus 6 (HHV-6) genome and hybridizing to all HHV-6 strains tested so far revealed homology to HHV-7 with only 37.4% of the total probe length. HHV-7 contains the GGGTTA repetitive sequence, as do HHV-6 and Marek’s disease chicken herpesvirus. DNA sequencing of a 186-base-pair fragment of HHV-7(JI) revealed an identity with HHV-6 and human cytomegalovirus of 57.5% and 36%, respectively. Oligonucleotide primers derived from this sequence (HV7/HV8, HV10/HV11) amplified HHV-7 DNA only and did not amplify DNA from other human herpesviruses, including 12 different HHV-6 strains. Southern blot analysis with the p43L3 probe containing the 186-base-pair HHV-7 DNA fragment hybridized to HHV-7 DNA only.

The molecular divergence between human cytomegalovirus, on the one hand, and HHV-6 and HHV-7, on the other, is greater than between HHV-6 and HHV-7, which, in turn, is greater than the difference between HHV-6 strains. This study supports the classification of HHV-7 as an additional member of the human beta-herpesviruses.

 

Source: Berneman ZN, Ablashi DV, Li G, Eger-Fletcher M, Reitz MS Jr, Hung CL, Brus I, Komaroff AL, Gallo RC. Human herpesvirus 7 is a T-lymphotropic virus and is related to, but significantly different from, human herpesvirus 6 and human cytomegalovirus. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10552-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC50377/ (Full article)

 

Chronic fatigue syndrome: studies on skeletal muscle

Abstract:

Chronic fatigue syndrome represents a poorly defined disease with protean clinical manifestations, the majority of them expressed as a muscle fatigue or as inability to maintain the expected muscle strength.

In the present work we studied muscle function and muscle histopathology in 20 patients fulfilling the proposed criteria for chronic fatigue syndrome. Special interest is directed towards the immunoreactive expression of class I MHC molecules comparing some inflammatory and virus-related myopathies with muscles from chronic fatigue syndrome.

Only minor morphological changes were detected in 9 out of 20 patients of the series. The nonspecific morphological changes in muscle tissue and the lack of class I MHC expression does not support the viral etiology of muscle fatigue in chronic fatigue syndrome. In contrast with the reported clinical improvement with high doses of essential fatty acids, our patients’ clinical condition did not improve after three months of L-carnitine therapy.

 

Source: Grau JM, Casademont J, Pedrol E, Fernández-Solà J, Cardellach F, Barros N, Urbano-Márquez A. Chronic fatigue syndrome: studies on skeletal muscle. Clin Neuropathol. 1992 Nov-Dec;11(6):329-32. http://www.ncbi.nlm.nih.gov/pubmed/1473316

 

Chronic fatigue syndrome, a case of high anti-HHV-6 antibody titer and one associated with primary hyperaldosteronism

Abstract:

Two cases of chronic fatigue syndrome (CFS) were reported which were suggestive for the study of the etiology and a cure for CFS.

Case 1: A 31-year-old woman was admitted for chronic fatigue syndrome. Examination revealed a high titer of anti HHV-6 antigen of x2560 and an increased percentage of suppressor T lymphocytes in the peripheral blood. HHV-6 was speculated to be reactivated and stimulating the immune system in CFS.

Case 2: A 46-year-old woman suffering from CFS had been in remission for 6 years. She was admitted for hypertension associated with right adrenal adenoma and hyperaldosteronism. After right adrenalectomy, there was a recurrence of high fever and other CFS symptoms. It was suggested that CFS symptoms may be ameliorated by aldosterone.

 

Source: Kato Y, Kamijima S, Kashiwagi A, Oguri T. Chronic fatigue syndrome, a case of high anti-HHV-6 antibody titer and one associated with primary hyperaldosteronism. Nihon Rinsho. 1992 Nov;50(11):2673-8. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1337563

 

Symptoms, signs and laboratory findings in patients with chronic fatigue syndrome

Abstract:

This review summarizes the symptoms, signs and laboratory abnormalities seen in 59 patients with chronic fatigue syndrome (CFS), 2 patients with post-infectious CFS and in 26 patients with possible CFS whose illnesses fulfill the criteria proposed by the study group of the Ministry of Welfare, Japan.

The characteristic symptoms and signs of CFS are prolonged generalized fatigue following exercise, headache, neuropsychological symptoms, sleep disturbance and mild fever. In possible CFS patients, the frequency of mild fever, muscle weakness, myalgia and headache is low.

Our standard hematologic and laboratory tests revealed a few abnormality in patients with CFS. The characteristic abnormality in CFS patients is the low values of 17-Ketosteroid-Sulfates/creatinine in morning urine and the acylcarnitine deficiency. It seems likely that this deficiency of acylcarnitine induces an energy deficit in the skeletal muscle, resulting in general fatigue, myalgia, muscle weakness and postexertional malaise in CFS patients. Virologic studies revealed no evidence of retrovirus infection with HTLV-1, HTLV-2 and HIV, but the reactivation of HHV-6 infection was apparent.

 

Source: Kuratsune H, Yamaguti K, Hattori H, Tazawa H, Takahashi M, Yamanishi K, Kitani T. Symptoms, signs and laboratory findings in patients with chronic fatigue syndrome. Nihon Rinsho. 1992 Nov;50(11):2665-72. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1337562