Acylcarnitine deficiency in chronic fatigue syndrome

Abstract:

One of the characteristic complaints of patients with chronic fatigue syndrome (CFS) is the skeletal muscle-related symptom. However, the abnormalities in the skeletal muscle that explain the symptom are not clear.

Herein, we show that our patients with CFS had a deficiency of serum acylcarnitine. As carnitine has an important role in energy production and modulation of the intramitochondrial coenzyme A (CoA)/acyl-CoA ratio in the skeletal muscle, this deficiency might induce an energy deficit and/or abnormality of the intramitochondrial condition in the skeletal muscle, thus resulting in general fatigue, myalgia, muscle weakness, and postexertional malaise in patients with CFS.

Furthermore, the concentration of serum acylcarnitine in patients with CFS tended to increase to the normal level with the recovery of general fatigue. Therefore, the measurement of acylcarnitine would be a useful tool for the diagnosis and assessment of the degree of clinical manifestation in patients with CFS.

 

Source: Kuratsune H, Yamaguti K, Takahashi M, Misaki H, Tagawa S, Kitani T. Acylcarnitine deficiency in chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S62-7. http://www.ncbi.nlm.nih.gov/pubmed/8148455

 

An approach to studies of cancer subsequent to clusters of chronic fatigue syndrome: use of data from the Nevada State Cancer Registry

Abstract:

Chronic fatigue syndrome (CFS) has been increasingly associated with immune dysregulation, including depressed natural killer cell activity; this phenomenon is associated with increased susceptibility to cancer. Although anecdotal reports have suggested an association between CFS and cancer, particularly non-Hodgkin’s lymphoma and brain cancer, there has been no a priori justification for evaluating such an association and no consideration of relevant parameters, such as length of latent period vs. tumor type.

We reviewed data from the Nevada State Cancer Registry subsequent to a reported outbreak of a CFS-like illness in Nevada that occurred during 1984-1986. We concentrated on non-Hodgkin’s lymphoma and brain/CNS tumors, with particular emphasis on persons 15-34 and 35-54 years of age.

An upward trend in the incidence of brain/CNS tumors, which could be related to a national upward trend for this disease, was noted. No consistent trends were noted for non-Hodgkin’s lymphoma.

Because of the difficulties inherent in studies of cancer subsequent to various exposures, we evaluated the methodology for determining an association between outbreaks of CFS-like disease and cancer. We propose several approaches that should be considered in future studies for investigation of possible associations between CFS and cancer, including expected latent periods for specific tumors.

 

Source: Levine PH, Atherton M, Fears T, Hoover R. An approach to studies of cancer subsequent to clusters of chronic fatigue syndrome: use of data from the Nevada State Cancer Registry. Clin Infect Dis. 1994 Jan;18 Suppl 1:S49-53. http://www.ncbi.nlm.nih.gov/pubmed/8148453

 

Concurrent sick building syndrome and chronic fatigue syndrome: epidemic neuromyasthenia revisited

Abstract:

Sick building syndrome (SBS) is usually characterized by upper respiratory complaints, headache, and mild fatigue. Chronic fatigue syndrome (CFS) is an illness with defined criteria including extreme fatigue, sore throat, headache, and neurological symptoms.

We investigated three apparent outbreaks of SBS and observed another more serious illness (or illnesses), characterized predominantly by severe fatigue, that was noted by 9 (90%) of the 10 teachers who frequently used a single conference room at a high school in Truckee, California; 5 (23%) of the 22 responding teachers in the J wing of a high school in Elk Grove, California; and 9 (10%) of the 93 responding workers from an office building in Washington, D.C.

In those individuals with severe fatigue, symptoms of mucous membrane irritation that are characteristic of SBS were noted but also noted were neurological complaints not typical of SBS but quite characteristic of CFS. We conclude that CFS is often associated with SBS.

 

Source: Chester AC, Levine PH. Concurrent sick building syndrome and chronic fatigue syndrome: epidemic neuromyasthenia revisited. Clin Infect Dis. 1994 Jan;18 Suppl 1:S43-8. http://www.ncbi.nlm.nih.gov/pubmed/8148452

 

A comparative review of systemic and neurological symptomatology in 12 outbreaks collectively described as chronic fatigue syndrome, epidemic neuromyasthenia, and myalgic encephalomyelitis

Abstract:

Outbreaks of illnesses of unknown etiology typified by a chronic relapsing course of constitutional symptoms and nervous system involvement have collectively been referred to as chronic fatigue syndrome, epidemic neuromyasthenia, and myalgic encephalomyelitis. To examine heterogeneity of clinical presentation, a comparative review was undertaken for 12 well-documented outbreaks reported since 1934.

A systemic syndrome characterized by excessive fatigue, myalgias, headache, low-grade fever, and other constitutional symptoms was common to cases in all outbreaks. However, marked heterogeneity in the range of neurological features was apparent.

On the basis of predominant neurological manifestations, outbreaks could be grouped into four levels of increasing neurological involvement: affective neuropsychological changes (level I); prominent cutaneous sensory symptoms with both affective and cognitive neuropsychological changes (level II); marked objective paresis with cutaneous sensory as well as affective and cognitive neuropsychological changes (level III); and cutaneous sensory, affective and cognitive neuropsychological, posterior column, cranial nerve, and mixed upper and lower motor neuron changes (level IV). Groups with the most prominent objective neurological findings (levels III and IV) comprised exclusively outbreaks reported between the 1930s and 1950s. All but one outbreak in groups with less prominent neurological findings (levels I and II) were reported between the 1960s and 1980s; a range of neurological features was observed for these groups.

Because a complete neurological examination is not emphasized as part of the diagnostic workup in current outbreaks, it is possible that less obvious neurological findings may be overlooked. Careful evaluation of neurological features in epidemic and endemic cases of what is now called chronic fatigue syndrome may be one approach to distinguishing subtypes of what has been described in the past as a nosological entity.

 

Source: Briggs NC, Levine PH. A comparative review of systemic and neurological symptomatology in 12 outbreaks collectively described as chronic fatigue syndrome, epidemic neuromyasthenia, and myalgic encephalomyelitis. Clin Infect Dis. 1994 Jan;18 Suppl 1:S32-42. http://www.ncbi.nlm.nih.gov/pubmed/8148451

 

Chronic fatigue syndrome and a disorder resembling Sjögren’s syndrome: preliminary report

Abstract:

Chronic fatigue syndrome (CFS), as currently described in the working criteria proposed by the Centers for Disease Control and Prevention (Atlanta), may be associated with multiple, distinct, and possibly unique clinical and/or etiopathogenic subsets.

Sjögren’s syndrome (SS) is a disease of unknown etiology that is characterized by dryness of the mucous membranes and a variety of autoimmune phenomena and conditions. Subjective manifestations of SS such as neurocognitive dysfunction and fatigue have been stressed by some observers. We have detected a large number of patients with unrecognized SS-like illness in a clinic specializing in CFS and believe the relationship to be more than casual.

From January 1991 through April 1992, 172 patients were evaluated for CFS; the SS cohort consisted of 27 females (mean age, 41.9 years). Sixteen of these patients had previously been found to have CFS by a physician, and 11 were self-referred. All patients complained of severe, dominating, chronic fatigue. Complaints of myalgia were prominent; 20 of 27 patients met the criteria for fibromyalgia. Neurocognitive complaints and/or a history of neuropsychiatric disease was frequent.

Results of Schirmer’s test were abnormal for 16 of 27, and results of minor salivary-gland biopsy were abnormal for 20 of 25. Antibodies to nuclear antigen were present in 16 of 27, but anti-Ro was present in only 1 of 21. In the SS group, 13 of 27 patients met eight or more CDC minor criteria for CFS, and 18 of 27 met six or more of the criteria.

We believe SS may represent a common and frequently overlooked clinical subset of CFS; however, further work is needed to define the similarities and/or differences between the SS observed in association with CFS and SS in the general population as well as the prevalence of SS among patients with CFS.

 

Source: Calabrese LH, Davis ME, Wilke WS. Chronic fatigue syndrome and a disorder resembling Sjögren’s syndrome: preliminary report. Clin Infect Dis. 1994 Jan;18 Suppl 1:S28-31. http://cid.oxfordjournals.org/content/18/Supplement_1/S28.abstract

 

Primary juvenile fibromyalgia syndrome and chronic fatigue syndrome in adolescents

Abstract:

Chronic fatigue syndrome (CFS) and primary juvenile fibromyalgia syndrome (PJFS) are illnesses with a similar pattern of symptoms of unknown etiology. Twenty-seven children for whom CFS was diagnosed were evaluated for fibromyalgia by the presence of widespread pain and multiple tender points.

Eight children (29.6%) fulfilled criteria for fibromyalgia. Those children who met fibromyalgia criteria had a statistically greater degree of subjective muscle pain, sleep disturbance, and neurological symptoms than did those who did not meet the fibromyalgia criteria. There was no statistical difference between groups in degree of fatigue, headache, sore throat, abdominal pain, depression, lymph node pain, concentration difficulty, eye pain, and joint pain.

CFS in children and PJFS appear to be overlapping clinical entities and may be indistinguishable by current diagnostic criteria.

 

Source: Bell DS, Bell KM, Cheney PR. Primary juvenile fibromyalgia syndrome and chronic fatigue syndrome in adolescents. Clin Infect Dis. 1994 Jan;18 Suppl 1:S21-3. http://www.ncbi.nlm.nih.gov/pubmed/8148447

 

Epidemic neuromyasthenia and chronic fatigue syndrome: epidemiological importance of a cluster definition

Abstract:

Outbreaks of illness variously identified by a number of terms, including epidemic neuromyasthenia, myalgic encephalomyelitis, Iceland disease, and atypical poliomyelitis, have been reported from many countries during the past 45 years.

Since the first well-described outbreak occurring in 1934, > 60 outbreaks have been reported, but few of these have been described in considerable detail. These outbreaks are usually cited in historical reports of chronic fatigue syndrome (CFS) since each of these outbreaks appears to contain a number of cases meeting the current case definition of CFS.

There has been inadequate attention given to the fact that epidemic neuromyasthenia and related clusters characterized by various complaints, including fatigue, do not have an accepted epidemiological or clinical definition, and only rarely have descriptions of these clusters included a specific case definition. When such case definitions have been applied, the occurrence of cases meeting the current case definition for CFS appears to be both variable and infrequent.

This report utilizes examples of several well-documented outbreaks to emphasize specific aspects that should be considered in the investigation of future clusters.

 

Source: Levine PH. Epidemic neuromyasthenia and chronic fatigue syndrome: epidemiological importance of a cluster definition. Clin Infect Dis. 1994 Jan;18 Suppl 1:S16-20. http://www.ncbi.nlm.nih.gov/pubmed/8148446

 

Decreased natural killer cell activity is associated with severity of chronic fatigue immune dysfunction syndrome

Abstract:

Natural killer (NK) cell activity was measured blindly in vitro with blood specimens from 50 healthy individuals and 20 patients with clinically defined chronic fatigue immune dysfunction syndrome (CFIDS) who met the criteria established by the Centers for Disease Control and Prevention (Atlanta).

In accordance with a group scoring system of 1-10 points, with 10 being the most severe clinical status, the patient population was stratified into three clinical groups: A (> 7 points), B (5-7 points), and C (< 5 points). NK cell activity was assessed by the number of lytic units (LU), which for the 50 healthy controls varied between 20 and 250 (50%, 20-50 LU; 32%, 51-100 LU; 6%, 101-130 LU; and 12%, > 150 LU).

In none of the 20 patients with CFIDS was the NK cell activity > 100 LU. For group C, the 10 patients stratified as having the least severe clinical condition, the measure was 61.0 +/- 21.7 LU; for group B (more severe, n = 7), it was 18.3 +/- 7.3 LU; and for group A (most severe, n = 3), it was 8.0 +/- 5.3 LU.

These data suggest a correlation between low levels of NK cell activity and severity of CFIDS, which, if it is confirmed by additional studies of larger groups, might be useful for subgrouping patients and monitoring therapy and/or the progression of CFIDS.

 

Source: Ojo-Amaize EA, Conley EJ, Peter JB. Decreased natural killer cell activity is associated with severity of chronic fatigue immune dysfunction syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S157-9. http://www.ncbi.nlm.nih.gov/pubmed/8148445

 

Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression

Abstract:

Among a group of 70 individuals who met the criteria established by the Centers for Disease Control and Prevention (Atlanta) for chronic fatigue syndrome (CFS), 12%-28% had serum levels exceeding 95% of control values for tumor necrosis factor (TNF) alpha, TNF-beta, interleukin (IL) 1 alpha, IL-2, soluble IL-2 receptor (sIL-2R), or neopterin; overall, 60% of patients had elevated levels of one or more of the nine soluble immune mediators tested.

Nevertheless, only the distributions for circulating levels of TNF-alpha and TNF-beta differed significantly in the two populations. In patients with CFS–but not in controls–serum levels of TNF-alpha, IL-1 alpha, IL-4, and sIL-2R correlated significantly with one another and (in the 10 cases analyzed) with relative amounts (as compared to beta-globin or beta-actin) of the only mRNAs detectable by reverse transcriptase-coupled polymerase chain reaction in peripheral-blood mononuclear cells: TNF-beta, unspliced and spliced; IL-1 beta, lymphocyte fraction; and IL-6 (in order of appearance). These findings point to polycellular activation and may be relevant to the etiology and nosology of CFS.

 

Source: Patarca R, Klimas NG, Lugtendorf S, Antoni M, Fletcher MA. Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression. Clin Infect Dis. 1994 Jan;18 Suppl 1:S147-53. http://www.ncbi.nlm.nih.gov/pubmed/8148443

 

Cytokine production and fatigue in patients with chronic fatigue syndrome and healthy control subjects in response to exercise

Abstract:

We have studied the relationship between the cytokine production induced in vivo by prolonged isometric exercise and the symptom complex marked by fatigue in patients with chronic fatigue syndrome (CFS).

Twelve male patients and 13 matched male control subjects undertook an isometric hand-grip exercise protocol utilizing dynamometers. Subjects undertook 30 minutes of exercise, for which the target force was set at 40% of the maximal voluntary contraction and the duty cycle was 50%. Prior to, during, and for 24 hours following the exercise, blood samples were collected and assayed for the presence of cytokines, including interferon-gamma and interferon-alpha, interleukin-1 beta, and tumor necrosis factor-alpha. At those times subjects also completed the Profile of Mood States (POMS) questionnaire, which served as a measure of changes in subjective fatigue.

No significant alteration in the level of any of the cytokines in the plasma of patients or control subjects was detected before, during, or after exercise. Surprisingly, the patients’ levels of fatigue, depression, and confusion, as measured by the POMS, decreased in response to the exercise.

These data do not confirm the presence of an immunologic process correlating with the exacerbation of fatigue after exercise experienced by patients with CFS. Limitations in the study design and in the sensitivity of the cytokine assays may have affected our results.

 

Source: Lloyd A, Gandevia S, Brockman A, Hales J, Wakefield D. Cytokine production and fatigue in patients with chronic fatigue syndrome and healthy control subjects in response to exercise. Clin Infect Dis. 1994 Jan;18 Suppl 1:S142-6. http://www.ncbi.nlm.nih.gov/pubmed/8148442