Cognitive functioning is impaired in patients with chronic fatigue syndrome devoid of psychiatric disease

Abstract:

OBJECTIVE: To examine the effect of the presence or absence of psychiatric disease on cognitive functioning in chronic fatigue syndrome.

METHODS: Thirty six patients with chronic fatigue syndrome and 31 healthy controls who did not exercise regularly were studied. Subgroups within the chronic fatigue syndrome sample were formed based on the presence or absence of comorbid axis I psychiatric disorders. Patients with psychiatric disorders preceding the onset chronic fatigue syndrome were excluded. Subjects were administered a battery of standardised neuropsychological tests as well as a structured psychiatric interview.

RESULTS: Patients with chronic fatigue syndrome without psychiatric comorbidity were impaired relative to controls and patients with chronic fatigue syndrome with concurrent psychiatric disease on tests of memory, attention, and information processing.

CONCLUSION: Impaired cognition in chronic fatigue syndrome cannot be explained solely by the presence of a psychiatric condition.

 

Source: DeLuca J, Johnson SK, Ellis SP, Natelson BH. Cognitive functioning is impaired in patients with chronic fatigue syndrome devoid of psychiatric disease. J Neurol Neurosurg Psychiatry. 1997 Feb;62(2):151-5. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC486726/ (Full article)

 

High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: To elucidate the humoral immune response in patients with chronic fatigue syndrome (CFS), by identification and characterization of autoantibodies.

METHODS: Initial immunofluorescence histochemistry studies of sera using human HEp-2 cell substrate were followed by antibody class subtyping and colocalization studies with reference antibodies. Association of CFS autoantigens with insoluble cellular components was determined by in situ extraction of soluble components and subsequent immunofluorescence histochemistry studies on the extracted cell substrate.

RESULTS: Of 60 CFS patients, 41 (68%) were positive for antinuclear antibodies. Localization of nuclear staining was found at the nuclear envelope (52%), in reticulated speckles (25%), in nucleoli (13%), and in dense fine speckles (5%). Twenty-eight CFS sera (47%) also had antibodies to cytoplasmic antigens. The major cytoplasmic staining pattern was of the intermediate filament type (35%). The observed nuclear envelope pattern of staining co-localized with lamina-associated polypeptide 2 (an integral nuclear membrane protein), the reticulated speckle pattern co-localized with non-small nuclear RNP splicing factor SC-35, and the intermediate filament pattern co-localized with vimentin. The intermediate filament antigen was shown to be vimentin in immunoblotting experiments using recombinant human vimentin, and one of the nuclear envelope antigens was shown previously to be lamin B1. Fifty of the 60 CFS patients (83%) had antibodies to one or another of these antigens, all of which are relatively insoluble cellular antigens, whereas a control group of patients without chronic fatigue had a significantly lower frequency of such antibodies (17%).

CONCLUSION: The high frequency of autoantibodies to insoluble cellular antigens in CFS represents a unique feature which might help to distinguish CFS from other rheumatic autoimmune diseases.

Comment in: Incidence of antinuclear antibodies in Japanese patients with chronic fatigue syndrome. [Arthritis Rheum. 1997]

 

Source: von Mikecz A, Konstantinov K, Buchwald DS, Gerace L, Tan EM. High frequency of autoantibodies to insoluble cellular antigens in patients with chronic fatigue syndrome. Arthritis Rheum. 1997 Feb;40(2):295-305. http://www.ncbi.nlm.nih.gov/pubmed/9041942

 

Markers of inflammation and immune activation in chronic fatigue and chronic fatigue syndrome

Abstract:

OBJECTIVE: Chronic fatigue syndrome (CFS) has been hypothesized to result from immune activation. We examined the role of serum markers of inflammation and immune activation among patients with CFS and in those with chronic fatigue (CF) not meeting the case definition.

METHODS: Assays for soluble interleukin 2 (IL-2) receptor, IL-6, C-reactive protein, beta 2-microglobulin, and neopterin were performed in 153 fatigued patients in a referral clinic. Patients were classified according to whether they met criteria for CFS, reported onset of illness with a viral syndrome or had a temperature > 37.5 degrees C on examination.

RESULTS: Compared to control subjects, mean concentrations of C-reactive protein, beta 2-microglobulin, and neopterin were higher in patients with CFS (p < or = 0.01) and CF (p < or = 0.01). Results did not distinguish CFS from CF. IL-6 was elevated among febrile patients compared to those without this finding (p < or = 0.001), but other consistent differences between patient subgroups were not observed. The presence of several markers was highly correlated (p < 0.01).

CONCLUSION: Our findings that levels of several markers were significantly correlated points to a subset of patients with immune system activation. Whether this phenomenon reflects an intercurrent, transient, common condition, such as an upper respiratory infection, or is the result of an ongoing illness associated process is unknown. Overall, serum markers of inflammation and immune activation are of limited diagnostic usefulness in the evaluation of patients with CFS and CF.

 

Source: Buchwald D, Wener MH, Pearlman T, Kith P. Markers of inflammation and immune activation in chronic fatigue and chronic fatigue syndrome. J Rheumatol. 1997 Feb;24(2):372-6. http://www.ncbi.nlm.nih.gov/pubmed/9034999

 

Evidence for enteroviral persistence in humans

Abstract:

We have sought evidence of enteroviral persistence in humans. Eight individuals with chronic fatigue syndrome (CFS) were positive for enteroviral sequences, detected by PCR in two serum samples taken at least 5 months apart. The nucleotide sequence of the 5′ non-translated region (bases 174-423) was determined for each amplicon.

Four individuals had virtually identical nucleotide sequences ( > 97%) in both samples. The sequence pairs also each had a unique shared pattern indicating that the virus had persisted. In one individual (HO), it was clear that there had been infection with two different enteroviruses.

In the remaining three individuals, the lack of unique shared features suggested that re-infection had occurred, rather than persistence. With the exception of HO, the sequences fell into a subgroup that is related to the Coxsackie B-like viruses.

 

Source: Galbraith DN, Nairn C, Clements GB. Evidence for enteroviral persistence in humans. J Gen Virol. 1997 Feb;78 ( Pt 2):307-12. http://www.ncbi.nlm.nih.gov/pubmed/9018051

 

Disagreements still exist over the chronic fatigue syndrome

Editor—Although the ME Association welcomes the royal colleges’ unequivocal conclusion that the chronic fatigue syndrome is a genuine and disabling condition,1 we also agree that their report will “engender disagreement on both sides of the Atlantic.”2 We have no problem in accepting that the alternative name for the condition—myalgic encephalomyelitis (ME)—is pathologically incorrect, and this is a matter that we now intend to address. However, labels are important to patients as well as doctors, and support groups throughout the world are unanimous in their view that “chronic fatigue syndrome” is a totally inadequate way of describing the symptomatology and associated disability. The chronic fatigue syndrome may well become a dustbin diagnosis for anyone with chronic fatigue, and a new name that is acceptable to both doctors and patients clearly needs to be found.

You can read the full comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2125625/pdf/9006489.pdf

 

Source: Shepherd C. Disagreements still exist over the chronic fatigue syndrome. BMJ. 1997 Jan 11;314(7074):146. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2125625/pdf/9006489.pdf

 

The effects of fatigue on neuropsychological performance in patients with chronic fatigue syndrome, multiple sclerosis, and depression

Abstract:

The effects of fatigue on neuropsychological performance were examined in patients with fatiguing illnesses. Repeated testing with the Paced Auditory Serial Addition Test (PASAT; Gronwall, 1977) was employed over the course of a demanding neuropsychological testing session. It was hypothesized that if fatigue affects performance, one would expect to observe “blunting” of the PASAT practice effect.

Fifteen of the study participants live with chronic fatigue syndrome (CFS), 15 with multiple sclerosis (MS), 14 with depression (DEP), and 15 are healthy, sedentary controls. Overall PASAT performance was significantly reduced for CFS and DEP participants compared to controls, whereas mean performance did not differ across the three fatiguing illness groups. Degree of improvement across trials (i.e., practice effect) for the groups did not differ from controls’. Neither subjective fatigue or DEP were significantly related to PASAT performance.

These findings suggest that fatigue does not universally impair performance during neuropsychological assessment even in groups in which fatigue is a prominent symptom.

 

Source: Johnson SK, Lange G, DeLuca J, Korn LR, Natelson B. The effects of fatigue on neuropsychological performance in patients with chronic fatigue syndrome, multiple sclerosis, and depression. Appl Neuropsychol. 1997;4(3):145-53. http://www.ncbi.nlm.nih.gov/pubmed/16318477

 

Chronic fatigue syndrome: a 20th century illness?

Abstract:

The chronic fatigue syndrome has become the fin de siècle illness, now getting similar attention to that of neurasthenia, which dominated medical thinking at the turn of the century.

Myalgic encephalomyelitis was an early term introduced in the United Kingdom in 1957 for this state, but it had little or no public or professional prominence. Until then “chronic fatigue had become invisible”, with “no name, no known etiology, no case illustrations or clinical accounts in the medical textbook, no ongoing research activity–nothing to relate it to current medical knowledge”.

The reconstruction of chronic fatigue began in the mid-1980s, with the emergence of “chronic Epstein-Barr virus syndrome”, which was later converted to chronic fatigue syndrome. The former term, which first emerged in the mid-1980s, is now regarded as a misnomer and should be abandoned.

In the popular American literature the term “chronic fatigue and immune deficiency syndrome” is preferred by the most active of the patient lobbies, while myalgic encephalomyelitis continues to be the usual label in the United Kingdom.

The relevant research linking chronic fatigue syndrome with somatization is reviewed in this article. Understanding the nature of somatization can still shed some light on the meaning of chronic fatigue at the end of the 20th century.

 

Source: Wessely S. Chronic fatigue syndrome: a 20th century illness? Scand J Work Environ Health. 1997;23 Suppl 3:17-34. http://www.sjweh.fi/show_abstract.php?abstract_id=239 (Full article)

 

Increased concentrations of homocysteine in the cerebrospinal fluid in patients with fibromyalgia and chronic fatigue syndrome

Abstract:

Twelve outpatients, all women, who fulfilled the criteria for both fibromyalgia and chronic fatigue syndrome were rated on 15 items of the Comprehensive Psychopathological Rating Scale (CPRS-15). These items were chosen to constitute a proper neurasthenic subscale.

Blood laboratory levels were generally normal. The most obvious finding was that, in all the patients, the homocysteine (HCY) levels were increased in the cerebrospinal fluid (CSF). There was a significant positive correlation between CSF-HCY levels and fatiguability, and the levels of CSF-B12 correlated significantly with the item of fatiguability and with CPRS-15.

The correlations between vitamin B12 and clinical variables of the CPRS-scale in this study indicate that low CSF-B12 values are of clinical importance. Vitamin B12 deficiency causes a deficient remethylation of HCY and is therefore probably contributing to the increased homocysteine levels found in our patient group.

We conclude that increased homocysteine levels in the central nervous system characterize patients fulfilling the criteria for both fibromyalgia and chronic fatigue syndrome.

 

Source: Regland B, Andersson M, Abrahamsson L, Bagby J, Dyrehag LE, Gottfries CG. Increased concentrations of homocysteine in the cerebrospinal fluid in patients with fibromyalgia and chronic fatigue syndrome. Scand J Rheumatol. 1997;26(4):301-7. http://www.ncbi.nlm.nih.gov/pubmed/9310111

 

Cytokine production by adherent and non-adherent mononuclear cells in chronic fatigue syndrome

Abstract:

It has been suggested that cytokines play a role in certain clinical manifestations of chronic fatigue syndrome (CFS). In this study adherent (monocytes) and non-adherent (lymphocytes) mononuclear cells were stimulated in the presence or absence of phytohemagglutinin (PHA) or lipopolysaccharide (LPS), respectively, and supernatants were assayed for IL-6, TNF-alpha, and IL-10 by ELISA. IL-6 was also measured at the mRNA level by polymerase chain reaction.

The levels of spontaneously (unstimulated) produced TNF-alpha by non-adherent lymphocytes and spontaneously produced IL-6 by both adherent monocytes and non-adherent lymphocytes were significantly increased as compared to simultaneously studied matched controls. The abnormality of IL-6 was also observed at mRNA level.

In contrast, spontaneously produced IL-10 by both adherent and non-adherent cells and by PHA-activated non-adherent cells were decreased. This preliminary study suggests that an aberrant production of cytokines in CFS may play a role in the pathogenesis and in some of the clinical manifestations of CFS.

 

Source: Gupta S, Aggarwal S, See D, Starr A. Cytokine production by adherent and non-adherent mononuclear cells in chronic fatigue syndrome. J Psychiatr Res. 1997 Jan-Feb;31(1):149-56. http://www.ncbi.nlm.nih.gov/pubmed/9201656

 

Double-blind randomized controlled trial to assess the efficacy of intravenous gammaglobulin for the management of chronic fatigue syndrome in adolescents

Abstract:

A double blind randomized controlled trial was conducted in 71 adolescents aged 11-18 years. Inclusion in the trial required fulfilment of the diagnostic criteria, (Fukuda et al., 1994).

Three infusions of 1 gm/kg (max 1 litre of 6 gm/100 ml in 10% w/v maltose solution) were given one month apart. The dummy solution was a 10% w/v maltose solution with 1% albumin of equivalent volume for weight. Efficacy was assessed by difference in a mean functional score including school attendance, school work, social activity and physical activity, between baseline, three months and six months after the final infusion.

There was a significant mean functional improvement at the six month follow-up of 70 adolescents with Chronic Fatigue Syndrome of average duration 18 months. There was also a significant improvement for both groups from the beginning of the trial to the six month post infusion follow-up. Adverse effects were common with both solutions but not predictive of response. Neither solution could be identified by recipients.

 

Source: Rowe KS. Double-blind randomized controlled trial to assess the efficacy of intravenous gammaglobulin for the management of chronic fatigue syndrome in adolescents. J Psychiatr Res. 1997 Jan-Feb;31(1):133-47. http://www.ncbi.nlm.nih.gov/pubmed/9201655