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Volume 2, Number 2 |
1st June 1999 |
Vojdani, A., Choppa, PC., Tagle, C., Andrin, R., Samimi, B and Lapp, CW. Detection of Mycoplasma genus and Mycoplasma fermentans by PCR in patients with chronic fatigue syndrome. FEMS Immunology and Medical Microbiology, 1998, 22, 4, 355-365.
Mycoplasma fermentans and other Mycoplasma species are colonisers of human mucosal surfaces and may be associated with human immunodeficiency virus infection. While many infectious agents have been described in different percentages of patients with CFS, little is known about the prevalence of mycoplasmas in this population. A polymerase chain reaction (PCR)-based assay was used to detect Mycoplasma genus and M. fermentans genomes in the peripheral blood mononuclear cells (PBMC) of 100 CFS patients (CDC criteria '94) and 50 healthy controls.
The amplified products of 717 bp of Mycoplasma genus, and 206 bp of M. fermentans were detected in 52% and 34% of CFS samples, respectively. In contrast, these genomes were found in only 14% and 8% of healthy control subjects respectively. All samples were confirmed by Southern blot with a specific probe based on internal sequences of the expected amplification product. Several samples, which were positive for Mycoplasma genus, were negative for M. fermentans, indicating that other Mycoplasma species are involved.
A quantitative PCR was developed to determine the number of M. fermentans genome copies present in 1 ug of DNA for controls and CFS patients. Mycoplasma copy numbers ranging from 130 to 880 and from 264 to 2400 were detected in controls and CFS positive subjects, respectively. An enzyme immunoassay was applied for the detection of antibodies against p29 surface lipoprotein of M. fermentans to determine the relationship between M. fermentans genome copy numbers and antibody levels.
Individuals with high genome copy numbers exhibited higher IgG and IgM antibodies against M. fermentans specific peptides. Isolation of this organism by culture from clinical specimens is needed in order to demonstrate specificity of signal detected by PCR in this study.
Wallace, HL 2nd., Natelson, B., Gause, W and Hay, J. Human herpes-viruses in chronic fatigue syndrome. Clinical and Diagnostic Laboratory Immunology, 1999, 6, 2, 216-223.
The authors conducted a double-blind study to assess the possible involvement of the human herpesviruses HHV6, HHV7, Epstein-Barr virus (EBV) and cytomegalovirus, in 122 CFS patients (CDC criteria '94) and 105 healthy age, gender and race matched controls. Both groups included people who had served in the Gulf War.
No significant differences were found between CFS patients and controls. This observation was upheld when the CFS populations were further stratified with regard to the presence or absence of major axis I psychopathology and patient self-reported gradual versus acute onset of disease.
Baraniuk, JN., Clauw, D., Yuta, A., Ali, M., Gaumond, E., Upadhyayula, N., Fujita, K and Shimizu, T. Nasal secretion analysis in allergic rhinitis, cystic fibrosis, and nonallergic fibromyalgia/chronic fatigue syndrome subjects. American Journal of Rhinology, 1998, 12, 6, 435-440.
Rhinitis symptoms are present in approximately 70% of subjects with fibromyalgia and CFS (FM/CFS). Because only 35% to 50% have positive allergy skin tests, nonallergic mechanisms may also play a role. To better understand the mechanisms of nonallergic rhinitis in FM/CFS, nasal lavages were performed, and markers of vascular permeability, glandular secretion, and neutrophil and eosinophil infiltration were measured in 27 patients with nonallergic FM/CFS (CDC criteria '94), 7 subjects with allergic rhinitis, 7 people with cystic fibrosis, and 9 normal subjects.
There were no differences in the basal secretion of the markers of vascular permeability, submucosal gland serous cell secretion, eosinophil and neutrophil degranulation in nonallergic FM/CFS subjects. This suggests that constitutively active secretory processes that regulate continuous production of nasal secretions are not altered in FM/CFS.
Gupta, S., Aggarwal, S and Starr, A. Increased production of interleukin-6 by adherent and non-adherent mononuclear cells during 'natural fatigue' but not following 'experimental fatigue' in patients with chronic fatigue syndrome. International Journal of Molecular Medicine, 1999, 3, 2, 209-213.
In an investigator-blinded study, adherent (monocytes) and non- adherent cells (lymphocytes) from 10 patients with CFS (CDC criteria '88) were examined on two separate occasions, namely when feeling 'fatigued' and when feeling 'rested'. Interleukin-6 (IL-6) production was assessed in vitro with and without phytohemagglutinin (PHA, for lymphocytes), and lipopolysaccharide (LPS, for monocytes). A group of 5 CFS patients and 4 controls were also subjected to exercise-induced fatigue ('experimental fatigue') and IL-6 production was compared, in a double-blinded manner, prior to and following induction of fatigue.
A significant increase in spontaneous, PHA- and LPS-induced IL-6 secretion by both lymphocytes and monocytes was observed in CFS patients during 'natural fatigue' as compared to the 'rested' state. However, no such changes in IL-6 production were observed during 'experimental fatigue'.
These data suggest a role of IL-6 in the symptomatology and perhaps in the pathogenesis of CFS. In addition, the data demonstrate that laboratory-induced fatigue may not be a good model to study immunological changes in CFS; immunological parameters should be studied in a longitudinal manner during the natural course of the disease.
See also LaManca, JJ et al. Immunological response in chronic fatigue syndrome following a graded exercise test to exhaustion. Journal of Clinical Immunology 1999, 19, 2, 135-142.
This study compared 20 patients with CFS and 14 sedentary controls following a treadmill exercise test. No group differences were found on any of the immune variables assessed.
Zhang, Q., Zhou, XD., Denny, T., Ottenweller, JE., Lange, G., LaManca, JJ. Lavietes, MH., Pollet, C., Gause, WC and Natelson, BH. Changes in immune parameters seen in Gulf War veterans but not in civilians with chronic fatigue syndrome. Clinical and Diagnostic Laboratory Immunology, 1999, 6, 1 6-13.
The aim of this study was to evaluate immune function in patients with CFS. The samples comprised Gulf War veterans (n=43) and civilians with CFS (n=68, CDC criteria '94), as well as healthy controls from the Gulf War (n=34) and community (n=53).
The researchers found no significant difference for any of the immune variables in the nonveteran population. In contrast, veterans with CFS had significantly more total T cells and MHC II+ T cells and a significantly higher percentage of the various lymphocyte sub-populations, as well as a significantly lower percentage of NK cells, than the respective controls. In addition, veterans with CFS had significantly higher levels of IL-2, IL-10, IFN-g, and TNF-a than the controls. There was no evidence of a shift from type 1 to a type 2 cytokine response or support for earlier research showing a certain difference between acute and gradual onset CFS.
"These data do not support the hypothesis of immune dysfunction in the genesis of CFS for sporadic cases of CFS but do suggest that service in the Persian Gulf is associated with an altered immune status in veterans who returned with severe fatiguing illness".
Abu-Judeh HH., Levine S., Kumar M., El-Zeftawy H., Naddaf S., Lou JQ and Abdel-Dayem HM. Comparison of SPET brain perfusion and 18F-FDG brain metabolism in patients with chronic fatigue syndrome. Nuclear Medicine Communications, 1998, 19, 11, 1065-71.
The researchers studied 99Tcm-HMPAO single photon emission tomography (SPET) brain perfusion with dual-head 18F-FDG brain metabolism in 18 patients with CFS (CDC criteria).
Thirteen patients had abnormal SPET brain perfusion scans and five had normal scans. Fifteen patients had normal glucose brain metabolism scans and three had abnormal scans.
They conclude that, in CFS patients, there is discordance between SPET brain perfusion and 18F-FDG brain uptake. It is possible to have brain perfusion abnormalities without corresponding changes in glucose uptake.
Sarkar, SN and Seastrunk, JW. Development of radiology markers to assess clinically diagnosed chronic fatigue syndrome. Nuclear brain SPECT and magnetic resonance spectroscopy results. Rivista di Neuroradiologia, 1998, 11 (Suppl. 2), 60-65.
This study compared the SPECT and MRI scans of 150 patients with CFS (CDC criteria '88 and '94) and people with idiopathic chronic fatigue and related disorders (fibromyalgia, chemical sensitivity). The results were compared with those of 20 age-matched controls.
The MRI scans on patients with infection-related CFS showed increased lactate and choline, often with a slight decrease in creatine. Other evidence indicated some toxicity perhaps affecting liver function. Neurotoxicity was associated with a depletion or elevation of GABA or glutamates in one or more location. SPECT scans revealed left frontal and temporal hypoperfusion in CFS, irrespective of causes (infection, chemical exposure). Certain abnormalities were associated with memory loss, depression and moderate/severe balance disorders.
De Becker, P., De Meirleir, K., Joos, E., Campine, I., Van Steenberge, E., Smitz, J and Velkeniers, B. Dehydroepiandrosterone (DHEA) response to i.v. ACTH in patients with chronic fatigue syndrome. Hormone and Metabolic Research, 1999, 31, 1, 18-21.
In order to investigate the dynamic response of the adrenal glands, the researchers measured serum levels of dehydroepiandrosterone (DHEA) at intervals during 60 minutes after adrenocorticotropic hormone (ACTH) stimulation. The subjects were 22 patients with CFS (CDC criteria '88 and '94, severely affected, most post-viral onset, no psychiatric illness) and 14 healthy controls.
The patients had normal basal DHEA levels but a blunted serum DHEA response curve to i.v. ACTH injection (p=.002).
"This observation adds to the large amount of evidence of endocrinological abnormalities in CFS. Relative glucocorticoid deficiency might contribute to the overall clinical picture in CFS, and could explain some of the immunological disturbances observed in this syndrome".
Schondorf, R., Benoit, J., Wein, T and Phaneuf, D. Orthostatic intolerance in the chronic fatigue syndrome. Journal of the Autonomic Nervous System, 1999, 75, 192-201.
This study investigated the prevalence and pathophysiology of orthostatic intolerance (OI) and its effects on symptoms in a group of 75 patients with CFS (CDC criteria '94) and 48 healthy controls. Laboratory investigation consisted of beat-to-beat recordings of heart rate, blood pressure (Finapres), and stroke volume (impedance cardiograph) while supine and during 80 degrees head-up tilt (HUT), during rhythmic deep breathing (6 breaths/min) and during the Valsalva manoeuvre.
Forty percent of patients with CFS had OI during head-up tilt. Sixteen exhibited neurally-mediated syncope alone, seven tachycardia (> 35 bpm averaged over the whole of the head-up tilt) and six a mixture of tachycardia and syncope. Eight of 48 controls exhibited neurally-mediated syncope. The responses to the Valsalva manoeuvre and to deep breathing were similar in controls and patients. On average, the duration of disease and patient age were significantly less and the onset of symptoms was more often subacute in patients with OI than in those without OI.
The researchers conclude that there exists a clinically identifiable subgroup of patients with CFS and OI that differs from control subjects and from those with CFS without OI.
See also Schondorf, R and Freeman, R. American Journal of the Medical Sciences, 1999, 317, 2, 117-123.
This review discusses the link between CFS and OI. The authors note that symptoms of OI, such as disabling fatigue, dizziness, diminished concentration, tremulousness and nausea, are often found in patients with CFS. Patients with OI may represent a subgroup of CFS, but the aetiology is unclear. Deconditioning may play a limited role.
Jason, LA., King, CP., Frankenberry, EL., Jordan, KM., Tryon, WW., Rademaker, F and Huang, CF. Chronic fatigue syndrome: assessing symptoms and activity level. Journal of Clinical Psychology, 1999, 55, 4, 411-424.
Current approaches to the diagnosis and assessment of CFS rely primarily on scales that measure only the occurrence of various symptoms related to CFS. Such approaches do not provide information on either the severity of symptoms or on fluctuations in symptom severity and activity level that occur over time. As a result, these measures do not reflect the complexities and the interrelations among symptoms. By obscuring the fluctuating nature of CFS and its high variability, current assessment procedures may prevent health care professionals from understanding the complexities of this disease.
The present study compared two patients with CFS (CDC criteria '94) with a healthy control on a fatigue scale and a symptom severity scale. Activity levels were measured using an actigraph (worn for 15 days).
There were notable differences between the patients and control. Useful information was obtained by assessing symptom severity on two occasions (current and worst period).
[Ed. note: The authors also report that in one group of 179 healthy adults, 15% met the CDC '94 criteria for CFS.]
Kelly, KS., Soderlund, K., Albert, C and McGarrahan, AG. Social support and chronic fatigue syndrome. Health Communication, 1999, 11, 1, 21-34.
Forty-one patients with CFS (not defined), 25 of whom had a primary support giver, completed a number of questionnaires including the Beck Depression Inventory (BDI), the Profile of Mood States (POMS), and the Inventory of Socially Supportive Behaviors (ISSB). The primary support giver completed a modified version of the ISSB indicating the level of support he or she provided and a questionnaire assessing beliefs about CFS.
There were no differences among individuals with CFS with or without support on measures of mood and perceived stress. People with CFS and their support givers agreed on the amount of support offered, and the extent of support was independent of beliefs concerning aetiology. The actual levels of support were lower than expected from the data on the ISSB.
[Ed. note: The results may have been confounded by the large proportion of patients with depressive mood (71%). Depression can affect the perception of social support. There was no measure of the quality of support.
Lovell, DM. Chronic fatigue syndrome among overseas development workers: a qualitative study. Journal of Travel Medicine, 1999, 6, 16-23.
According to the author, a relatively high proportion of overseas development workers may develop CFS (1.7-3%)*. A qualitative study was conducted in order to investigate how such people perceived their condition.
Twelve individuals who had developed CFS (Oxford criteria) while working overseas with development organisations, or shortly after visiting development projects, were interviewed about their experiences. They also completed a number of questionnaires, including the BDI. The results were compared with those of 129 returned overseas workers who did not develop CFS. Two patients were taking antidepressants and 3 had recovered by the time of testing. The mean duration of illness was 25 months.
Most of the participants considered themselves to have been extremely healthy before they developed CFS. The syndrome did not appear to have been caused by depression and there was no difference in BDI scores between the two groups at the time of testing.
The symptoms which were reported covered the range of symptoms typically found in studies of CFS. Respondents described difficulty in receiving and accepting a diagnosis. All of the participants attributed the CFS to multiple causes, the principal ones being overwork, stress and infections. However, many mentioned that although busy, they enjoyed the work and felt happy. Among the consequences of CFS reported to be the most difficult were having to leave the development project prematurely, pain, powerlessness, loss of independence, and the unpredictability of CFS. Factors which had helped respondents cope with these difficulties included religious beliefs, comparisons with people who were worse off than they were, thinking about positive consequences of the condition, and talking with supportive people. Also helpful were: adequate rest, an activity schedule with realistic goals, dietary guidelines, sunshine and alternative therapies (massage, yoga etc.).
There was no evidence for the view that the symptoms represented an attempt to escape from responsibilities without having to admit that life is too demanding (cf. Surawy et al). Moreover, there was no evidence of avoidance and the author suggests that the latter may be a strategy associated with depression (which was not a factor in this subgroup).
Further research on the aetiology of CFS is warranted. Respondents described high levels of work-related stress as common to the experience of development work. It might be beneficial to train development workers in stress management techniques. Development organisations should be encouraged to ensure that their workers take sufficient time to rest, and attempts should be made to reduce work pressures.
* [Ed. note: The figures given are actually very similar to the prevalence of CFS in the general population.]
Smith, AP., Borysiewicz, L., Pollock, J., Thomas, M., Perry, K and Llewelyn, M. Acute fatigue in chronic fatigue syndrome patients. Psychological Medicine, 1999, 29, 2, 283-290.
This study assessed the performance on cognitive tests of 67 patients with CFS (Oxford criteria, no requirement of post-exertional fatigue) and 126 matched healthy controls. The tests were chosen because they are sensitive to sleep loss and other forms of acute fatigue. Acute fatigue was assessed by comparing performance at the start and end of a lengthy session and by examining changes over the course of individual tasks. Other measures included the PFRS and BDI (mean of patients: 14.4).
The CFS patients showed impaired performance compared to the controls and these differences increased as the volunteers developed acute fatigue. In addition, differences between the two groups were larger at the end of the test session.
"The present results show that CFS patients are more susceptible to acute fatigue than healthy controls. This could reflect motor fatigue or an inability to compensate for fatigue with increased effort. This profile is consistent with previous research on fatigue and suggests that interpretation of certain aspects of CFS may be helped by considering it as the end point of a continuum of fatigue rather than a distinct disease*."
[Ed. note: There is no information on the influence of depression or the levels of cortisol (which may have been a relevant factor since 41% reported stress as a cause of their illness). Moreover, there is no analysis of the data according to any of the subgroups as recommended by the CDC '94. *Due to the heterogeneity of the sample, it is difficult to interpret the results in relation to subgroups like infection-related CFS or ME].
Kawakami, N., Iwata, N., Fujihara, S and Kitamura, T. Prevalence of chronic fatigue syndrome in a community population in Japan. Tohoku Journal of Experimental Medicine, 1998, 186, 1, 33-41.
In order to assess the prevalence CFS in a community population in Japan, the researchers analysed data from a population-based interview survey.
Two cases out of 137 respondents experienced chronic fatigue during a period of nine months, reported a 50% or more reduction of daily activity due to fatigue and had no other physical or psychiatric diagnosis. Both these cases fulfilled the Oxford and CDC criteria '94. The point and nine-month prevalence rates of CFS were both 1.5%. No person fulfilled the CDC criteria '88. The prevalence rate of CFS was higher than those in previous studies in the Western countries, suggesting a need for future research on cross-cultural differences in the definition, prevalence and symptomatology of CFS.
Forsyth, LM., Preuss, HG., MacDowell, AL., Chiazze, L Jr., Birkmayer, GD and Bellanti, JA. Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome. Annals of Allergy, Asthma & Immunology, 1999, 82, 2, 185-191.
The purpose of the study was to evaluate the efficacy of the reduced form of nicotinamide adenine dinucleotide (NADH) i.e., ENADA the stabilised oral absorbable form, in a randomised, double-blind, placebo-controlled crossover study in patients with CFS. NADH is known to trigger energy production through ATP generation which may form the basis of its potential effects.
Twenty-six patients (CDC criteria '94, 96% with post-exertional malaise, 81% with allergies) completed the study. Medical history, physical examination, laboratory studies and questionnaires were obtained at baseline, 4, 8, and 12 weeks. Subjects were randomly assigned to receive either 10 mg of NADH or placebo for a 4-week period. Following a 4-week washout period, subjects were crossed to the alternate regimen for a final 4-week period.
No severe adverse effects related to the study drug were observed. Within this cohort of 26 patients, 8 (31%) responded favourably to NADH (10% improvement) in contrast to 2 (8%) to placebo. At baseline, levels of urinary 5HIAA were elevated in 50% of patients. After treatment, the levels returned to normal. Based upon these encouraging results, the researchers began an open-label study in a larger cohort of patients. Early results suggest that 72% made significant improvements.
Collectively, the results of this pilot study indicate that NADH may be a valuable adjunctive therapy in the management of the CFS.
Gibson, SLM and Gibson, RG. A multidimensional treatment plan for chronic fatigue syndrome. Journal of Nutritional & Environmental Medicine, 1999, 9, 47-54.
This pilot study involved 81 consecutive patients with CFS (Oxford criteria, 65% viral trigger). They had not benefited from conventional treatments.
The first month, they were placed on a wheat-free diet plus supplements including Co-enzyme Q10, oil of evening primrose and Magnesium OK. This regime was maintained during the second month but any inhalant allergies were also treated (homoeopathically). During the third month, constitutional homeopathic remedies were added (one dose monthly). During the fourth month, psychotherapeutic techniques were introduced, aimed at improving self-image, and this was maintained for the next two months. Measures included the General Health Questionnaire-30, Spielberger State Anxiety Questionnaire, and the Personal Health Questionnaire.
Twenty-one per cent of patients dropped out of the trial. Of those who completed the study (n=64), the duration of illness was 1.7 years. Just over a half (57.8%) had positive prick tests to house dust. Ten also had positive responses to grass pollens. In all, 70% of those who completed the trial reported a clinical improvement. This was particularly the case during the first month. Women improved more than men and fewer of the responders had allergies (NS). No patient deteriorated.
The wheat-free diet and supplements appeared to be the most useful components of the regime, but from month 4 onwards, there was little change, suggesting that the psychotherapeutic interventions were not so helpful. Allergies and viral triggers made no significant difference to the outcome.
Natelson, BH., Cheu, J., Hill, N., Bergen, M., Korn, L., Denny T and Dahl K. Single-blind, placebo phase-in trial of two escalating doses of selegiline in the chronic fatigue syndrome. Neuropsychobiology, 1998, 37, 3 150-154.
Twenty-six patients with CFS (modified CDC criteria '88, '94) received placebo or selegiline (5mg), a specific monoamine oxidase (MAO) B receptor inhibitor. Measures included a questionnaire assessing functioning (FSQ), a depression scale (CES-D), POMS, and the Illness Severity Scale. The trial was done in three 2-week blocks: in the first, 2 placebo pills were given per day; in the next, one 5-mg tablet of agent and one placebo were given per day, and in the last, the agent was given twice a day. Six patients dropped out.
There was a significant improvement in 3 variables: tension/anxiety, vigour and sexual relations. A significant pattern of improvement was found for the 19 self-report vehicles during active treatment as compared with placebo. However, evidence for an antidepressant effect of the drug was not found. "Selegiline has a small but significant therapeutic effect in CFS which appears independent of an antidepressant effect."
Warren, G., McKendrick, M and Peet, M. The role of essential fatty acids in chronic fatigue syndrome. Acta Neurologica Scandinavica, 1999, 99, 2, 112-116.
The aim of this study was to replicate the trial by Behan et al (1990).
Fifty patients with CFS (Oxford criteria) were randomly allocated to treatment with either Efamol Marine (500 mg, 2 capsules 4x a day) or placebo (sunflower oil) for 3 months. They were seen monthly and completed a physical symptoms checklist and the BDI. They were also asked if they were the same, better or worse at the end of the study.
Symptoms generally improved with time but not significantly and there were no significant differences between the treatment and placebo groups. Pre-treatment red-cell membrane (RBC) lipids of patients compared with age- and sex-matched normal controls showed no significant differences.
The results of this study contrast sharply with the previous study (on PVFS) where 85% of patients had a clinically significant improvement of symptoms with Efamol Marine over a 3-month period.
Cramer, CR. Fibromyalgia and chronic fatigue syndrome: An update for athletic trainers. Journal of Athletic Training, 1998, 33, 4. 359-361.
Short review focused on athletes.
Goshorn, RK. Chronic fatigue syndrome: a review for clinicians. Seminars in Neurology, 1998, 18, 2, 237-242.
Short, balanced review focusing on current issues.
McCluskey, DR. Chronic fatigue syndrome: its causes and a strategy for management. Comprehensive Therapy, 1998, 24, 8, 357-363.
Personal view of CFS and its management. The author suggests that CFS is a sleep disorder due to serotonin deficiency.
[Ed. note: There is no evidence of a serotonin deficiency in patients with CFS. Levels have generally been found to be normal or above normal, and therapeutic doses of drugs which increase serotonin are often poorly tolerated. Moreover, the author's estimate of the prevalence of depression is much higher than the literature suggests. Although cases of CFS as described here may begin in Autumn or Winter, the onset of cases of ME are more common between May and November.]
Andersson, M., Bagby, JR., Dyrehag, LE and Gottfries, CG. Effects of Staphylococcus toxoid vaccine on pain and fatigue in patients with fibromyalgia/chronic fatigue syndrome. European Journal of Pain, 1998, 2, 133-142.
Positive results of pilot studies assessing the effect of staphylococcus toxoid vaccine in patients with fibromyalgia and CFS were the incitement to the present study. It involved 28 patients who fulfilled criteria for both fibromyalgia and CFS (CDC criteria '88?). The effect of vaccination with a staphylococcus toxoid was compared with the effect of injections of sterile water.
Significant improvements were seen on a psychopathological rating scale (CPRS) in the vaccine group. There were also improvements in clinical global impressions and group differences for fatiguability (item on the CPRS).
In a follow-up study of 23 patients, the vaccine treatment was continued for 2-6 years. Fifty per cent were rehabilitated successfully and resumed half-time or full-time work.
The results of this study support the authors' hypothesis that treatment with staphylococcus toxoid may be a fruitful strategy in patients with fibromyalgia and CFS.
Baraniuk, J., Naranch, K., Velarde, A and Clauw, D. Rhinitis in chronic fatigue syndrome (CFS). Journal of Allergy and Clinical Immunology, 1999, 103 (1 pt 2), S196, 754.
Abstract reporting that patients with CFS and fibromyalgia have more rhinitis-type symptoms than healthy people and that they may be more sensitive to irritants.
Baschetti, R. Psychological factors and chronic fatigue syndrome. New Zealand Medical Journal, 1999, 112, 58-59.
Letter responding to an article by Clarke (ibid., 1998, 111, 410-412). Baschetti notes that the positive results with CBT may reflect the use of broad criteria which do not discriminate between CFS and depression. Accordingly, those helped by CBT may have had depression, rather than CFS. He also discusses the similarity between CFS with Addison's disease, noting the value of drugs like hydrocortisone.
With reply by Clarke, emphasising the need to consider psychological and social factors in all chronic disorders.
Chaudhuri, A and Behan, PO. Chronic fatigue syndrome is an acquired neurological channelopathy. Human Psychopharmacology -Clinical and Experimental, 1999, 14, 1, 7-17.
Review article noting that the fatigue in CFS is distinct from the fatigue of neuromuscular disorders but similar to that found in disorders of the central nervous system such as multiple sclerosis, Parkinson's disease and multiple system atrophy. Though fatigue is a common symptom of depressive disorders, it is now clear that CFS patients differ from patients with major depression in their symptoms, biological markers such as steroid metabolism and response to standard antidepressant drug therapy. In this paper, the authors propose dysfunctional ion channels in the cell membranes as the key abnormality in CFS which may also be responsible for the altered neuroendocrine functions reported in this condition.
In this hypothesis, changes in the neuronal ion channel function from time to time offer a rational basis to explain fluctuating fatigue and related symptoms in CFS. Finally, ion channel abnormality leading to selective neuronal instability may be the common disease mechanism in CFS and other paroxysmal disorders affecting brain functions such as migraine and epilepsy.
Cuykx, V., Van Houdenhove, B and Neerinckx, E. Childhood abuse, personality disorder and chronic fatigue syndrome. General Hospital Psychiatry, 1998, 20, 6, 382-384.
Letter describing a patient with CFS, a history of child abuse, and current psychiatric disorders including agoraphobia. A multidimensional approach, including medication, activities and psychodynamically oriented psychotherapy was helpful for a time.
Giardino, ND., Fielder, NL., Lehrer, PM and Kelly-McNeil, K. Effects of chemical and psychological stress on Persian Gulf Veterans with Chronic Fatigue Syndrome (Abstract). Psychosomatic Medicine, 1999, 61, 1, 121.
Report on a study of US Persian Gulf veterans, some of whom had CFS. They were exposed to 5 ppm of diesel mixture. The group with CFS reported significantly higher symptom levels associated with indoor air quality (e.g. runny nose) than healthy veterans. The groups did not differ on symptoms at baseline or after one hour post exposure. The veterans with CFS showed attenuated heart rate and blood pressure reactivity and recovery after exposure and testing with a psychological stressor. They also demonstrated greater reactivity in heart rate variability. The physiological measures were higher at baseline in the CFS group and remained higher throughout the tests. The absolute differences between the groups on physiological measures were probably due to CFS status although the pattern of responses may have been influenced by negative affectivity (NA).
Hill, S. The superwoman and the victim. The European Journal of Oriental Medicine, 1998, 1, 3, 46-49.
Case histories of two women with ME from a Chinese medical perspective.
Hotopf, M and Wessely, S. Chronic fatigue syndrome - mapping the interior. Psychological Medicine, 1999, 29, 2, 255-258.
Short editorial discussing the various articles in Psychological Medicine, and underlining the complexity of CFS.
[Ed. note: this editorial focuses on CFS but discusses several studies on people without CFS (e.g. Hickie et al).]
Jordan, KM., Mears, CJ., Katz, B., Ayers, P and Taylor, K. Prevalence of chronic fatigue syndrome-like illness in a community-based sample. (Abstract). Journal of Adolescent Health, 1999, 24, 2, 153.
A survey amongst 18,675 households in Chicago revealed a prevalence rate of CFS-like illness of 2.4% for adolescents and 1.96% for children under 13. The male:female ratio was similar.
Pagani, M and Lucini, D. Chronic fatigue syndrome: a hypothesis focusing on the autonomic nervous system. Clinical Science, 1999, 96, 1, 117-125.
In CFS, there are reported disturbances in autonomic activity, and in other homoeostatic mechanisms, such as the hormonal and immune systems. There are alterations in cardiovascular autonomic control, as can be assessed by spectral analysis of R-R interval and systolic arterial pressure variability. According to the authors, indices of sympathetic modulation could provide quantifiable signs of the interaction between subject's efforts and environmental demands, independently of self descriptions, which could provide convenient measurable outcomes, both for diagnosis and treatment titration.
Streeten, DHP. Orthostatic Intolerance. A historical introduction to the pathophysiological mechanisms. American Journal of the Medical Sciences, 1999, 317, 2, 78-87.
Review. Several of the pathophysiological mechanisms resulting in OI (i.e. tachycardia) have been recognised individually over the course of the past 100 years or more. More recent definitions of the normal ranges of orthostatic blood pressure and heart rate changes have facilitated the recognition of pathogenetic disorders that are probably shared in various proportions between OI and various types of orthostatic hypotension. These include autonomic dysfunction of (1) the leg veins almost invariably causing excessive gravitational blood pooling, usually associated with (2) hypovolemia of circulating erythrocytes and plasma that is probably attributable to impaired autonomic stimulation of erythropoietin production, renin release, and (less consistently) aldosterone secretion. Improved understanding of these apparent results of lower body dysautonomia should facilitate more effective therapy in the future.
Various. Hydrocortisone and chronic fatigue syndrome. Lancet, 1999, 353, 1618-1619.
Letters responding to the study by Cleare et al (ibid., p. 455).
Bell, IR., Baldwin, CM., Russek, LGS., Schwartz, GER and Hardin, EE. Early life stress, negative paternal relationships, and chemical intolerance in middle-aged women: support for a neural sensitisation model. Journal of Women's Health, 1998, 7, 9, 1135-1147.
This study compared early life stress ratings, parental relationships, and health status, notably orthostatic blood pressures, of middle-aged women with low-level chemical intolerance (CI group) and depression, depressives without CI (DEP group), and normal controls.
One neurobehavioural model for CI is neural sensitisation, that is, the progressive amplification of host responses (e.g. behavioural, neurochemical) to repeated intermittent stimuli (e.g. drugs, chemicals, endogenous mediators, stressors). Females are more vulnerable to sensitisation than are males.
Both the CI and DEP groups had high levels of life stress and past abuse while the CI group had the most distant and weak relationships with the father. Only the CI group showed sensitisation of sitting blood pressures over sessions. Together with prior evidence, these data are consistent with a neural sensitisation model for CI in certain women. The findings may have implications for poorer long-term medical as well as neuropsychiatric health outcomes of a subset of women with CI. Subsequent research should test this model in specific clinical diagnostic groups with CI.
Farmer, A., Scourfield, J., Martin, N., Cardno, A and McGuffin, P. Is disabling fatigue in childhood influenced by genes? Psychological Medicine, 1999, 29, 279-282.
A survey of the parents of 670 twin pairs (aged 5-17) revealed that 6.9% of the individuals experienced a period of disabling fatigue, and that in 2.5%, this lasted at least one month. The results also showed that fatigue is highly familial, though there was a marked influence of a shared environment.
Hickie, I., Kirk, K and Martin, N. Unique genetic and environmental determinants of prolonged fatigue: a twin study. Psychological Medicine, 1999, 29, 2, 259-268.
This study involved 1004 normal adult twin pairs (533 monozygotic, 471 dizygotic) over 50 years of age. The results indicated that fatigue lasting at least one month may be related, at least in part, to genetic factors. In total, 44% of the genetic variance for fatigue was not shared by the other forms of distress measured (e.g. anxiety and depression). Similarly, the environmental factor determining psychological distress made negligible contributions to fatigue, which was underpinned largely by its own independent environmental factor.
See also Hickie et al (ibid. p. 269-277). This study involved 124 adult twin pairs who underwent delayed-type hypersensitivity skin response (DTH) testing, and completed the GHQ-12 and a fatigue questionnaire (SOFA).
There were strong genetic influences on psychological distress and fatigue, but only some were common to both. Indeed, an independent genetic factor contributed to fatigue only. Immune responsiveness arose mainly from environmental factors shared by both twins. The view of a straightforward relationship between distress and immune function is therefore rather simplistic and needs to take the host's genotype into account. In relation to fatigue syndromes, the findings support the notion that "such disorders may constitute relatively independent forms of distress".
Quinter, JL and Cohen, ML. Fibromyalgia falls foul of a fallacy. Lancet, 1999, 353, 1092-1094.
Viewpoint article in which the authors argue that the concept of fibromyalgia needs clarification.
Henningsen, P and Priebe, S. Modern disorders of vitality: the struggle for legitimate incapacity. Journal of Psychosomatic Research, 1999, 46, 3, 209-214.
Editorial covering disorders like CFS and multiple chemical sensitivity, which appear to have no obvious explanation but where the patients "persist" in attributing the complaints to a physical cause. The conditions in question "are not part of the official classification of diseases"1. According to the authors, they represent a "primary expression of disturbed relations of a person to his or her environment."
Focusing on chronic fatigue, the authors note that many doctors prefer "psychiatric explanations". They go on to state that patients are currently fighting for legitimacy through self-help groups, the media, the internet, politics as well as the law. This "fierce" campaign increasingly "bypasses both medicine as a science and medical institutions"2.
The authors suggest two reasons for the current campaign. The first is the wish to avoid the stigma of mental illness. The second is the need to avoid the illegitimate part of the complaint: the underlying meaning, e.g. not wishing to do something. They also link it to the failure to achieve personal or professional goals. However, since using tiredness as an excuse is not acceptable to the patient, this has to be disguised.
They point to an apparent paradox: on the one side, the patients claim to be very tired but on the other, they "show remarkable vigor" in their fight for legitimacy. This must not be a sign of conscious simulation, though it's understandable if one recalls their goal, namely, "reaching legitimate incapacity"3. The authors also note the importance of professional success in this culture. They wonder how one would have diagnosed CFS in the 'hippie' generation when pleasure was more important than professional performance4.
Finally, they suggest that proponents of disorders like CFS and MCS are challenging the biomedical model, by proposing new theories which are incompatible with current toxicology, or by bypassing evidence-based medicine completely via the courts. Accepting the accounts of incapacity as valid may help to understand the behaviour of patients and thus improve communication.
[Ed. notes:
1. This is inaccurate. ME (the term which preceded CFS) is listed in ICD-10 (WHO).
2. This is an unrealistic argument. Medical and science journals rarely give space to patients' opinions about their illness, whether it be CFS or cancer. The point about bypassing medical institutions is inconsistent with the facts. In the UK, patient groups have helped to organise and fund postgraduate seminars at hospitals and medical schools. Patients are regularly consulted by various institutions, and several sit on the Chief Medical Officer's Working Group on CFS. In recent years, only the Royal Colleges Working Party has refused to consult with them.
3. There is obviously a confusion here between CFS and TATT (tired all the time) as well as an assumption that tiredness is the main source of disability in CFS. It might also be worth noting here that disability does not mean inability. During the eighties, patients with AIDS mounted an effective campaign for the recognition of their illness, despite being severely ill.
4. During the sixties, the illness in question was called myalgic encephalomyelitis or ME. The medical literature on this condition goes back to the thirties. It was first defined in 1956 (Lancet) and recognised as a disease in 1992 (WHO).
General points:
The authors ignore all the evidence implicating an organic aetiology, apparently assuming that there is no medical evidence for the existence of disorders like CFS. They also ignore the fact that the fatigue syndrome called ME occurs in epidemics. This means that they do not discuss why and how personal feelings of failure might occur in outbreaks, particularly between May and November. Nor do they attempt to explain symptoms such as low grade fevers, sore throats and intolerance to alcohol.
This article appears to be based almost entirely on ignorance concerning CFS and MCS, disinformation and personal prejudice. It will almost certainly reduce understanding and add to the stigmatisation of patients. Scientists and mental health professionals who are familiar with the literature may find this article deeply insulting and grossly offensive. Moreover, by relying on ill-informed psychobabble and ignoring all the research which contradicts their view, the article undermines the reputation of psychiatry as a medical speciality, based on science.]
In my view, this editorial is medicine's equivalent of racism. Of course, people are entitled to their opinion, however controversial they may be. Still, is it acceptable in 1999 for a medical journal to publish an article which contains misleading information, which stigmatises a particular patient group and for which there is no scientific evidence?1 And if this is acceptable, should the editors be forced to publish corrections, and allow someone to express the opposite view?The article in question was not an opinion piece written by experienced specialists in the field. It was classed as an editorial and penned by outsiders. Why was it accepted by the editors in that form? What were they trying to achieve? Given its message was that there is nothing physically wrong with these people and that they are using illness as an excuse, how did they think this might improve the interaction with patients? Did they really believe that references to "fierce" campaigns and attempts to "bypass evidence-based medicine" would make doctors more sympathetic to those affected? Did they think that by reducing the illness to fatigue, tiredness and a lack of vitality, doctors would have a greater understanding of their patients' distress?
One thing we can say is that the editors cannot plead ignorance. One of the British editors co-authored a paper on CFS and the other was a member of the working party which drew up the Royal Colleges Report. I'm sure that both knew enough about the literature to realise that the editorial was revisionist, unfair and inaccurate in parts. So why did they accept it as an editorial? Why did they not commission a second article to provide some balance2?
It seems as though the authors responded to the threat of an ill-understood disease like laymen. This could explain why they used defence mechanisms like denial ('it's not new, it's not a disease and it's not genuinely disabling'), psychologisation and 'blaming the victim'3. It's all terribly primitive and more importantly, it's inconsistent with good science!
I also think there's evidence of prejudice. Mankind may be able to get to the moon but when it comes to new diseases, most of us prefer simple explanations and we prefer them cheap. That's probably why British medical journals have tended to turn a blind eye when writers on CFS ignore relevant research, change the odd fact here and there, and support their theory with clumsy generalisations and ridiculous stereotypes. It's no longer acceptable to write defamatory articles about people with AIDS, but it appears to be perfectly permissible to insult patients with CFS. It won't lead to criticisms from colleagues, let alone disciplinary action or dismissal. Admittedly, a few individuals might write the odd angry letter and some patients may express their disgust on the internet. However, that's about it. The authors refer to campaigns, but these have generally focused on gaining recognition for benefits purposes. To describe these as 'fierce' is overstating it. In fact, given the attacks on their integrity over the years, the reaction of these patients has been remarkably benign4. Basically, they're sitting targets, and that's how they'll remain until someone complains to the GMC, or sues a doctor for defamation, libel or malicious falsehood!
Just as there was no pressure on the British media or judicial system to challenge the fervent anti-Semitism before the war, or the 'unwitting' racism in the police prior to the Lawrence case, there's no desire to present balanced and accurate information about CFS in the medical press. Why? Because there's no one in a position of influence who is insisting that editors stick to the rules of science. It's also easy to dismiss dissenting voices; in this case, the authors just implied that CFS specialists are as misguided as their patients (cf. p.214) and that their research should therefore be ignored.
There's no correspondence section in this journal, so unless the editors print a response, readers will remain blissfully ignorant of this paper's flaws. Why does that make me angry? Because it's not just a matter of a difference of opinion; an alternative interpretation of the research. I must have read 99% of all the articles and books on CFS and there's no scientific evidence for the views expressed. Absolutely none! The theory in question is based on anecdotal reports, other people's opinions and one of the most criticised studies in the field. Would that be acceptable if we were discussing controversial statements about a certain ethnic group? Would that type of evidence justify upsetting people with cancer or AIDS? Of course, it wouldn't!
What people say to each other in private is one thing. What they write for publication is another5. The British press have a Code of Conduct, discouraging inaccurate, misleading or distorted material, racism and sexism. However, the code doesn't cover the medical journals, and that gives them carte blanche to write what they like!
In my opinion, biased editorials like this must be challenged because they undermine people's understanding of the illness and stigmatise patients6. They reinforce existing prejudices and create new ones. They trivialise the illness, and by alluding to somatisation, they encourage antipathy and disbelief. In short, the editorial harms the people affected and damages them psychologically. One would expect psychiatrists to be sensitive to that and to be the last people on this earth to write articles based on prejudice. Sadly, the evidence speaks for itself7.
On the positive side, this astonishing lack of respect for the rules of science seems to be limited to British journals. Moreover, anyone wishing to find more balanced and accurate information on CFS can do so quite easily, by accessing Medline (free, via the internet), or by reading American journals or publications aimed at other health professionals8. As ever, the antidote to prejudice is knowledge, and that's also true in relation to CFS.
To conclude, articles like the one above represent a primitive response to a threat. They give an illusion of control, but the reassurance they offer is false and transient. Since such accounts distort reality, doctors cannot understand their patients' experiences, nor make informed decisions about treatment. In my view, this problem arose because the various authors and editors disregarded their scientific training. It will be very interesting to see who or what will persuade them to change!
EMG
Notes
1. For information about stigmatisation, see Goffman's book Stigma (Penguin 1963, ch.1). Evidence that the authors stigmatise patients with CFS includes the portrayal of the fatigued population as being homogeneous (e.g. references to "the exhausted patient", "the proponents", and the failure to acknowledge that there are a significant number of individuals to whom the theory does not apply). Furthermore, there's the implication that many members of this population are inferior, deviant and a threat to others (cf. they use CFS as an excuse, references to a fierce campaign, court cases, fighting against sensible doctors and modern medicine). The authors also discredit the patients, implying that most are somatising, prejudiced against mental illness, manipulative and untrustworthy.2. I nominate Prof. David Mechanic, who is the world authority on illness behaviour. At a conference, he challenged the theory that CFS represents a flight-into-illness by observing that there are easier and more efficient ways of opting out of the rat race than claiming to have CFS. He also documented the tendency of some doctors to blame patients if the cause of their illness was unclear. See Bock and Whelan. Chronic Fatigue Syndrome. John Wiley & Sons. 1993, p. 78.
3. References detailing the prejudicial (non-scientific) views of doctors and the origins of victim-blaming theories can be found in various sources, including Goudsmit and Gadd, The Psychologist, 1991, 4, 449-453. Prejudice is defined in the OED as a preconceived opinion, premature judgement, bias or partiality.
4. There may have been legal cases in relation to MCS, but as far as CFS is concerned, court action has been limited to obtaining disability benefits and pensions. I'm not aware of mass tomato throwing, marches through London, or any other organised activities which could be described as 'fierce'.
5. This does not only apply to the written word. What people can say in public is also limited. The England football coach Glenn Hoddle lost his job because of his religious beliefs, which he discussed with a journalist and which the Times deemed to be offensive to the disabled.
6. For more information about the editorial bias in British medical journals, see Read, C. ME/PVFS and the Press. This is an independent report commissioned and published by Action for ME (1993).
7. I accept that some psychiatrists are sensitive to this problem. However, have they noted their disagreement by writing to medical journals? I cannot recall any article during the past five years which was written by psychiatrists and which challenged the stigmatisation of CFS or the somatisation theory. Is this just a result of editorial bias? In contrast, there have several publications by psychologists and other mental health professionals with critical comments about simplistic psychiatric explanations, e.g. Lovell (above), Saltztein et al 1998, and Friedberg and Jason (1998). Incidentally, chartered psychologists are prohibited from making public statements about psychological matters which conflict with the scientific evidence (para 5.7 of the Code of Conduct).
8. See, for example, the American Journal of Medicine, 1998, 105, 3A and Jason et al, American Psychologist, 1997, 52, 973-983.
*The opinions expressed are those of the author and do not necessarily reflect the views of the editorial team. The London editor of the Journal of Psychosomatic Research was given an opportunity to respond but chose not to.
This issue was compiled by Dr. EM Goudsmit, Dr. A. Macintyre and Mrs S. Howes. We gratefully acknowledge the help and support from Dr. C. Shepherd, the Haworth Press and Mr. D. Axford.
The ME and CFS Capita Selecta Quarterly is funded by donations.
Copyright EM. Goudsmit 1999.
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Psychologist/Archivist, London.
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