Tag: review

Immunity and the pathophysiology of chronic fatigue syndrome

Abstract:

The pathophysiology of chronic fatigue syndrome (CFS) remains unknown. The syndrome often follows a recognized or presumed infection and the disorder may therefore result from a disordered immune response to a precipitating infection or antigenic challenge.

Abnormalities of both humoral and cellular immunity have been demonstrated in a substantial proportion of patients with CFS. The most consistent findings are of impaired lymphocyte responses to mitogen and reduced natural killer cell cytotoxicity. Cutaneous anergy and immunoglobulin G subclass deficiencies have also been found.

Further studies are needed examining cytokine levels in serum and cerebrospinal fluid, and cytokine production in vitro in patients with CFS. Interpretation of the findings of published studies of immunity is limited by probable heterogeneity in the patient groups studied, and by the lack of standardization and reproducibility in the assays used.

The pattern of abnormalities reported in immunological testing in patients with CFS is consistent with the changes seen during the resolving phases of acute viral infection. These data provide circumstantial support for the hypothesis that CFS results from a disordered immune response to an infection. Longitudinal studies of immunity in patients developing CFS after defined infectious illnesses will provide the best means of further examining this hypothesis.

 

Source: Lloyd AR, Wakefield D, Hickie I. Immunity and the pathophysiology of chronic fatigue syndrome. Ciba Found Symp. 1993;173:176-87; discussion 187-92. http://www.ncbi.nlm.nih.gov/pubmed/8491097

 

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

 

Chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is defined by symptoms and diagnosed without any objective diagnostic tests. Risk factors for developing CFS may include infection, psychiatric disorders, and allergies. Modest dysfunction of multiple organ systems, including the immune, central nervous, endocrine, and muscular systems, have been identified in cases of CFS. Symptoms of various organic, psychiatric, and poorly understood disorders overlap those of CFS. There is no known cure for CFS; however, exercise, counseling, and medications may provide symptomatic relief.

 

Source: Klonoff DC. Chronic fatigue syndrome. Clin Infect Dis. 1992 Nov;15(5):812-23. http://www.ncbi.nlm.nih.gov/pubmed/1445980

 

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

 

Viral infection and its causative role for chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS), of unknown etiology, have been increasingly reported. This syndrome is characterized by debilitating fatigue, lymphadenopathy, and fever. Herein, I focus on and review this syndrome from the view point of the causative role of viral infection. Since the symptoms of CFS are similar to those of chronic infectious mononucleosis (CIM) or chronic Epstein-Barr virus infection (CEBV), the role of EBV has been intensively studied. The etiological relationship between EBV and CFS, however, is questioned, like other lymphotropic viruses, including human retroviruses, adenoviruses and human herpesvirus 6. Additionally, severe chronic active EBV infection syndrome (SCAEBV) is also discussed in this review because symptoms of this disorder are similar to those of CFS but more severe in degree. Currently, the cause(s) and treatment of CFS are enigmatic and require further research and multidisciplinary study.

 

Source: Okano M. Viral infection and its causative role for chronic fatigue syndrome. Nihon Rinsho. 1992 Nov;50(11):2617-24. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1337559

 

Chronic fatigue syndrome and virus infection: human herpesvirus 6 (HHV-6) infection

Abstract:

Chronic fatigue syndrome (CFS) is newly-recognized disease characterized by chronic and debilitating fatigue. It has been suggested that viral infection may be involved in this syndrome from the results of clinical examination, including increased activity of 2′,5′-synthetase in leukocytes of patients. The following viruses have been reported as etiologic agents of this disease. First, many studies have found elevated levels of IgG to viral capsid antigen and early antigens to Epstein-Barr virus (EBV), but low titer or absence of antibody to EBV-associated nuclear antigen. Second, the enteroviruses have also been implicated as possible causative agent of CFS, because virus could be isolated from patients. Recently it was also reported that antibodies to human T-lymphotropic virus (HTLV) and HTLV type II (HTLV-II) gag sequence were detectable in patients. Finally several reports state that human herpesvirus 6 (HHV-6) could be isolated from CFS patients in the high frequency. In conclusion, it is still early to identify the etiologic agent from these reports, and more effort is needed.

 

Source: Yamanishi K. [Chronic fatigue syndrome and virus infection: human herpesvirus 6 (HHV-6) infection]. Nihon Rinsho. 1992 Nov;50(11):2612-6. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1337558

 

Therapy of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is characterized by unexplained, debilitating fatigue or easy fatigability lasting longer than six months. While a number of clinical trials have been performed in CFS patients, there is currently no established therapy for CFS. Treatment with acyclovir of CFS patients is ineffective. Intravenous immunoglobulin therapy appears to be effective, though the results are controversial. Antidepressants might help the associated depression and anxiety but not other symptoms. Trials with magnesium have improved the well-being of patients. Restoration of NK activity by biological response modifiers, such as sizofirann, resulted in restoration of NK cell activity and recovery from CFS. Taken together, immunological abnormalities may be involved in CFS, and its restoration may produce clinical benefit in CFS.

 

Source: Uchida A. Therapy of chronic fatigue syndrome. Nihon Rinsho. 1992 Nov;50(11):2679-83.[Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1287242

 

Neuro-psychiatric aspects of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is easily differentiated from various neurological organic disorders by conventional clinical examinations. The most important disease for distinguishment from CFS is fibromyalgia syndrome, in which the prominent and cardinal feature is a deprivation of stage 4 slow wave sleep.

Experimentally, the sleep disturbance in controls can induce general myalgia, muscle tender points, severe fatigue and stiffness on awakening. The EEG abnormality is slow alpha wave contaminants on slow wave background, which is identical to EEG of CFS. The results clearly imply that CFS is not a hysterical or psychogenic disease, and that fibromyalgia may be a central fundamental of CFS.

Fibromyalgia, however, has distinct features such as no antecedent inflammatory process and no endemics. Therefore, the syndrome has features distinct from, in addition to common features to CFS. It is also very difficult to distinguish CFS from depression. The above-mentioned features can be observed in depression. Now, study of brain blood flow or metabolism by PET or SPECT can be a possible tool for establishment of the CFS identity.

 

Source: Shimizu T. Neuro-psychiatric aspects of chronic fatigue syndrome. Nihon Rinsho. 1992 Nov;50(11):2630-4. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1287239

 

Chronic fatigue immune dysfunction syndrome

Abstract:

Chronic fatigue syndrome (CFS) is characterized by unexplained, debilitating fatigue or easy fatigability lasting longer than six months. While a viral basis of infection is proposed to be the cause of CFS, other viral infections do not generally persist after several weeks.

Immunological disorders, including abnormal functions and distributions of T lymphocytes, B lymphocytes, natural killer (NK) cells, and monocyte/macrophages, are described in CFS. NK cells are known to play an important role in host resistance against viral infection as well as in the regulation of the immune systems.

Restoration of NK activity resulted in recovery from CFS. Taken together, immunological abnormalities, especially dysfunction of NK cells, may be involved in CFS.

 

Source: Uchida A. Chronic fatigue immune dysfunction syndrome. Nihon Rinsho. 1992 Nov;50(11):2625-9. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1287238