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IMMUNOLOGY
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Vernon, SD., Shukla, SK., Conradt, J., Unger, ER and Reeves, WC. Analysis of 16S rRNA gene sequences and circulating cell-free DNA from plasma of chronic fatigue syndrome and non-fatigued subjects. BMC Microbiology 2002, 2, 1, 39.
BACKGROUND: The association of an infectious agent with CFS has been difficult and is further complicated by the lack of a known lesion or diseased tissue. Cell-free plasma DNA could serve as a sentinel of infection and disease occurring throughout the body. This type of systemic sample coupled with broad‑range amplification of bacterial sequences was used to determine whether a bacterial pathogen was associated with CFS. Plasma DNA from 34 CFS (CDC criteria '94) and 55 non‑fatigued subjects was assessed to determine plasma DNA concentration and the presence of bacterial 16S ribosomal DNA (rDNA) sequences.
RESULTS: DNA was isolated from 81 (91%) of 89 plasma samples. The 55 non‑fatigued subjects had higher plasma DNA concentrations than those with CFS (average 151 versus 91 ng) and more CFS subjects (6/34, 18%) had no detectable plasma DNA than non‑fatigued subjects (2/55, 4%), but these differences were not significant. Bacterial sequences were detected in 23 (26%) of 89. Only 4 (14%) CFS subjects had 16S rDNA sequences amplified from plasma compared with 17 (32%) of the non‑fatigued (p=0.03). All but 1 of the 23 16S rDNA amplicon‑positive subjects had five or more unique sequences present.
CONCLUSIONS: CFS subjects had slightly lower concentrations or no detectable plasma DNA than non-fatigued subjects. There was a diverse array of 16S rDNA sequences in plasma DNA from both CFS and non-fatigued subjects. There were no unique, previously uncharacterized or predominant 16S rDNA sequences in either CFS or non-fatigued subjects.
Schmaling, KB., Lewis, DH., Fiedelak, JI., Mahurin, R and Buchwald, DS. Single-photon emission computerized tomography and neurocognitive function in patients with chronic fatigue syndrome. Psychosomatic Medicine, 2003, 65, 1, 129-136.
OBJECTIVE: The purposes of this study were to compare functional imaging under control and experimental conditions among patients with CFS and healthy persons and to examine perceived and objective performance on a test of attention and working memory previously found to be difficult for persons with CFS.
METHODS: Single-photon emission computerized tomography scans were completed on 15 subjects with CFS (CDC criteria '94) and 15 healthy persons twice: at rest and when performing the Paced Auditory Serial Addition Test (PASAT).
RESULTS: No group differences were found for performance on the PASAT despite CFS subjects' perceptions of exerting more mental effort to perform the task than healthy subjects. Inspection of the aggregate scans by group and task suggested a pattern of diffuse regional cerebral blood flow among subjects with CFS in comparison with the more focal pattern of regional cerebral blood flow seen among healthy subjects. Between-group region-of-interest analysis revealed that although CFS subjects showed less perfusion in the anterior cingulate region, the change in CFS subjects' activation of the left anterior cingulate region during the PASAT was greater than that observed for healthy subjects. The differences were not attributable to lesser effort by the subjects with CFS, confounding effects of mood perturbation, or to poorer performance on the experimental task.
CONCLUSIONS: Further research regarding CFS subjects' diffuse cerebral perfusion and its relationship to inefficient neuropsychological performance is warranted.
Gaab, J., Huster, D., Peisen, R., Engert, V., Schad, T., Schurmeyer, TH and Ehlert, U. Low-dose dexamethasone suppression test in chronic fatigue syndrome and health. Psychosomatic Medicine, 2002, 64, 311-318.
METHODS: In 21 patients with CFS (Oxford and CDC criteria '94) and 21 healthy control subjects, awakening and circadian salivary free cortisol profiles were assessed over 2 consecutive days and compared with awakening and circadian salivary free cortisol profiles after administration of 0.5 mg of dexamethasone at 11:00 PM the previous day.
RESULTS: Patients with CFS had normal salivary free cortisol profiles but showed enhanced and prolonged suppression of salivary free cortisol after the administration of 0.5 mg of dexamethasone in comparison to the control subjects.
CONCLUSIONS: Enhanced negative feedback of the HPA axis could be a plausible explanation for the previously described alterations in HPA axis functioning in CFS. Because similar changes have been described in stress-related disorders, a putative role of stress in the pathogenesis of the enhanced feedback is possible.
Gaab, J., Huster, D., Peisen, R., Engert, V., Heitz, V., Schad, T., Schurmeyer, TH and Ehlert, U. Hypothalamic-pituitary-adrenal axis reactivity in chronic fatigue syndrome and health under psychological, physiological, and pharmacological stimulation. Psychosomatic Medicine, 2002, 64, 951-962.
OBJECTIVES: Subtle alterations of the HPA axis in CFS have been proposed as a shared pathway linking numerous etiological and perpetuating processes with symptoms and observed physiological abnormalities. Because the HPA axis is involved in the adaptive responses to stress and CFS patients experience a worsening of symptoms after physical and psychological stress, we tested HPA axis functioning with three centrally acting stress tests.
METHODS: We used two procedures mimicking real-life stressors and compared them with a standardized pharmacological neuroendocrine challenge test. CFS patients were compared with healthy control subjects regarding their cardiovascular and endocrine reactivity in a psychosocial stress test and a standardized exercise test, and their endocrine response in the insulin tolerance test (ITT).
RESULTS: Controlling for possible confounding variables, we found significantly lower ACTH response levels in the psycho-social stress test and the exercise test, and significantly lower ACTH responses in the ITT, with no differences in plasma total cortisol responses. Also, salivary-free cortisol responses did not differ between the groups in the psychosocial stress test and the exercise test but were significantly higher for the CFS patients in the ITT. In all tests CFS patients had significantly reduced baseline ACTH levels.
CONCLUSIONS: These results suggest that CFS patients are capable of mounting a sufficient cortisol response under different types of stress but that on a central level subtle dysregulations of the HPA axis exist.
[Ed. note: the patients did not report significantly increases in perception of effort, as one would expect given the current definition of CFS.]
Ciccone, DS., Buschio, K., Tiersky, L and Natelson, BN. Co-morbid unexplained illness in chronic fatigue syndrome. Evidence of multiple illness categories. Proceedings of the British Psychological Society, 2003, 11, 1, 25.
If CFS and fibromyalgia (FM) share the same aetiology, then a model of illness behaviour developed for CFS-only should apply to people with CFS\FM as well. The same factors should predict illness behaviour in both groups. Also, lifetime prevalence of major depression (MD) should be comparable.
The sample consisted of 80 consecutive female patients with CFS (CDC criteria). They completed several questionnaires plus a psychiatric interview. 34 subjects satisfied the criteria for FM (42.5%).
Symptom severity was similar in both groups. However, there were group differences in the prevalence of MD (61% versus 32% for CFS). Pain and fatigue scores explained 39% of the variance in illness behaviour in patients with CFS\FM compared to 20% for CFS only.
"These findings offer tentative support for the view that CFS and CFS/FM represent discrete illness categories."
Sundbom, E., Henningsson, M., Holm, U., Soderbergh, S and Evengard, B. Possible influence of defenses and negative life events on patients with chronic fatigue syndrome: a pilot study. Psychological Reports, 2002, 91 (3 Pt 1), 963-978.
13 patients with a diagnosis of CFS and two contrast groups of conversion disorder patients (n=19) and healthy controls (n=13) were assessed using the projective perceptual Defense Mechanism Test to investigate if specific defense patterns are associated with CFS. Another objective was to assess the possible influence of perceived negative life events prior the onset of the illness.
The overall results showed significant differences in defensive strategies among groups represented by two significant dimensions in a Partial Least Squares analysis. Compared to the contrast groups the patients with CFS were distinguished by a defense pattern of different distortions of aggressive affect, induced by an interpersonal anxiety-provoking stimulus picture with short exposures.
Their responses suggested the conversion group was characterized by a nonemotionally adapted pattern and specific constellations of defenses, associated with interior reality orientation compared to the patients with CFS and the healthy controls.
Rated retrospectively, the group with CFS reported significantly more negative life events prior to the onset of their illness than healthy controls. For instance, 5 of the 13 patients reported sexual assault or physical battery as children or teenagers compared to none of the healthy controls. A significant association was found between defense pattern and frequency of reported negative life events. However, these retrospective reports might be confounded to some extent by the experience of the patients' illness; for example, the reports may be interpreted in terms of present negative affect.
Taillefer, SS., Kirmayer, LJ., Robbins, JM and Lasry, JC. Psychological correlates of functional status in chronic fatigue syndrome. Journal of Psychosomatic Research, 2002, 53, 6, 1097-1106.
BACKGROUND: The present study was designed to test a cognitive model of impairment in CFS in which disability is a function of severity of fatigue and depressive symptoms, generalized somatic symptom attributions and generalized illness worry.
METHODS: We compared 45 CFS (CDC criteria '88) and 40 multiple sclerosis (MS) outpatients on measures of functional ability, fatigue severity, depressive symptoms, somatic symptom attribution and illness worry.
RESULTS: The results confirmed previous findings of lower levels of functional status and greater fatigue among CFS patients compared to a group of patients with MS. Fatigue severity was found to be a significant predictor of physical functioning but not of psychosocial functioning in both groups. In CFS, when level of fatigue was controlled, making more somatic attributions was associated with worse physical functioning, and both illness worry and depressive symptoms were associated with worse psychosocial functioning.
CONCLUSIONS: Our findings support the role of depression and illness cognitions in disability in CFS sufferers. Different cognitive factors account for physical and psychosocial disability in CFS and MS. The SF-36 may be sensitive to symptom attributions, suggesting caution in its interpretation when used with patients with ill-defined medical conditions.
[Ed. note: the two groups were not matched for level of disability and there were notable difference, not only in terms of fatigue. The MS group was not acutely ill. There are no data for number of patients with clinical depression and none for somatic symptoms. The text indicates an obvious preference for the CBT model, and ignores relevant findings to the contrary. For instance, the authors refer to increasing disability predicted by the model but do not note that CFS is generally not progressive. Indeed, their own findings show only 21% rated themselves worse compared to one year previously. The discussion emphasizes the maladaptive beliefs and behaviours such as avoidance of activity and wish to avoid responsibility - neither of which were actually studied - and basically blames the victims. There is no acknowledgement that CFS may actually be a physical disorder and that most patients' attributions may be correct.]
Allen, LA., Escobar, JI., Lehrer, PM., Gara, MA and Woolfolk, RL. Psychosocial treatments for multiple unexplained physical symptoms: a review of the literature. Psychosomatic Medicine, 2002, 64, 939-950.
Review of treatments including CBT for people with CFS, RA, IBS. Flaws are acknowledged. The authors note the "modest" effect sizes and question whether these treatments have a lasting and clinically meaningful influence on physical complaints of polysymptomatic somatizers. They discuss mechanisms such as attention, help for depression etc.
Evengard B and Klimas N. Chronic fatigue syndrome: probable pathogenesis and possible treatments. Drugs, 2002, 62, (17), 2433-2446.
Review. No link between infections and CFS has been clearly established but the immune system is activated, there are aberrations in several hypothalamic-pituitary axes and involvement of other parts of the central nervous system. No specific treatment has been found. CBT is established to be of value to improve quality of life.
Adler, GK., Manfredsdottir, VF and Rackow, RM. Hypothalamic-pituitary-adrenal axis function in fibromyalgia and chronic fatigue syndrome. Endocrinologist, 2002, 12, 6, 513-524.
Ferreira, AC and de Marchena, E. Grading autonomic dysfunction in chronic fatigue syndrome. Seminars in Arthritis and Rheumatism, 20002, 32, 3, 137-138.
Frey, DR. Chronic fatigue and depression. American Family Physician, 2002, 66, 10, 1838-1839.
Letter suggesting that CFS may be a form of somatized, atypical depression. With reply by Craig, JR noting that if depression is considered a cause, CFS cannot be diagnosed. Moreover, there are differences between CFS and depression.
Hundertmark, JD. Chronic fatigue syndrome clinical practice guidelines: psychological factors. Medical Journal of Australia, 2002, 177, 9, 525. Also letters by Hickie, IB (p. 526), Beard, DD.
Letters responding to correspondence surrounding the Australian guidelines for CFS (ibid p. 51). With reply by Larkins, RG and Mollesworth, SR (p. 526-7).
Katz, BZ. Update on chronic fatigue syndrome and Epstein-Barr virus. Pediatric Annals, 2002, 31, 11, 741-744.
Iversen, A and Wessely, S. Chronic fatigue and depression. Current Opinion in Psychiatry, 2003, 16, 17-21.
Short discussion of fatigue and depression, including some findings relating to CFS.
Jason, LA & Taylor RR. (2003). Chronic fatigue syndrome. In A. M. Nezu, C. M. Nezu, & P.A. Geller (Eds.). Handbook of Psychology, Volume 9: Health Psychology. (pp. 365‑391). Wiley: New York.
Masuda, A., Munemoto, T, Yamakana, T, Takei, M and Tei, C. Psychological characteristics and immunological functions in patients with post-infectious chronic fatigue syndrome and noninfectious fatigue syndrome. Journal of Behavioral Medicine, 2002, 25, 5, 477-485.
Differences between patients with post-infectious CFS (CDC criteria '92, n=16) and noninfectious CFS (n=20) were clarified.
The noninfectious CFS group had problems in family and developmental history, and had chronic stresses. Members of the post-infectious CFS group were social extroverts while those in the noninfectious CFS group was neurotic and introspective. Natural killer cell activity was suppressed in both groups compared to healthy controls (n=20).
These findings suggest that the post-infectious CFS group and the noninfectious CFS group differed in their pathogenesis until the onset of CFS. The latter group should be considered as a variant of psychiatric disorder and treated accordingly.
[Ed. note: The 'contamination' of the two groups e.g. by the inclusion of patients with significant recent stress in the infectious CFS group, means the conclusions should be interpreted with caution. The difference between the groups in terms of activity levels is noteworthy.]
Masuda, A., Nakayama, T., Yamanaka, T., Koga, Y and Tei, C. The prognosis after multidisciplinary treatment for patients with post-infectious chronic fatigue syndrome and noninfectious chronic fatigue syndrome. Journal of Behavioral Medicine, 2002, 25, 5, 487-497.
The prognosis after multidisciplinary treatment for patients with post-infectious CFS (CDC criteria 1992, n=9) and noninfectious CFS (n=9) was clarified.
After treatment (Chinese herbs, vitamin C, massage, biofeedback, drugs as required, family therapy, CBT, gentle graded exercise), natural killer (NK) cell activity increased in the post-infectious CFS group but did not recover to within normal range in the non-infectious CFS group. In the post-infectious CFS group, physical and mental symptoms improved, and 8 of the 9 patients returned to work. In the noninfectious CFS group, symptoms did not improve, and only 3 patients returned to work.
The prognosis of post-infectious CFS group was better than that of noninfectious CFS group. Classification of CFS patients into post-infectious and noninfectious groups is useful for choosing the appropriate treatment in order to obtain better prognosis.
[Ed. note: The infectious CFS group included people with considerable stress, while the non-infectious group included patients with chronic pancreatitis and Meniere's disease, both of which would not be expected to respond well to vitamin C, CBT etc. The former had been ill less long and the latter were much more inactive.]
McCue, P., Scholey, AB., Herman, C and Wesnes, KA. Validation of a telephone cognitive assessment test battery for use in chronic fatigue syndrome. Journal of Telemedicine and Telecare, 2002, 8, 6, 337-343.
We compared a computerized version of the Cognitive Drug Research (CDR) cognitive assessment test battery and a completely automated telephone version of the same battery. These assessed aspects of attention, working memory and long-term memory. Both methods were used to assess the cognitive performance of a cohort of 30 people with confirmed CFS and a group of 30 healthy controls matched for age and education.
The CFS group had significantly slower reaction times on all four cognitive measures on both the computerized and telephone tests. The mood data followed similar patterns in the computer and telephone assessments. The results from both forms of the test battery confirmed the pattern and severity of cognitive impairment in CFS. Furthermore, the two methods of testing were similarly sensitive in detecting cognitive deficits. The incapacitating nature of CFS may cause problems for researchers if the restrictions to mobility affect the representativeness of the study group. The findings of the present study support the use of a fully automated telephone cognitive testing system for detecting deficits in CFS.
Naschitz, JE., Sabo, E., Naschitz, S., Rosner, I., Rozenbaum, M., Madelain, F., Hillel,. I, Priselac, RM., Gaitini, L., Eldar, S., Zukerman, E and Yeshurun D. Hemodynamics instability score in chronic fatigue syndrome and in non-chronic fatigue syndrome. Seminars in Arthritis and Rheumatism, 2002 32, 3, 141-148.
OBJECTIVE: In studying patients with CFS we developed a method that confers numerical expression to the degree of blood pressure and heart rate lability, ie, the 'hemodynamic instability score' (HIS). The HIS in CFS patients differed significantly from healthy subjects. The present investigation compares the HIS in CFS, non-CFS chronic fatigue and patients with recurrent syncope.
METHODS: Patients with CFS (n=21), non‑CFS chronic fatigue (n=24), syncope of unknown cause (n=44), and their age and sex-matched healthy controls (n=21) were evaluated with a standardized head-up tilt test (HUTT). Abnormal reactions (endpoints) on HUTT were classified 'clinical outcomes' (cardioinhibitory or vasodepressor reaction, orthostatic hypotension, postural tachycardia syndrome) and 'HIS endpoint', i.e. HIS > -0.98.
RESULTS: The highest incidence of endpoints was noted in patients with CFS (79%), followed by patients with syncope of unknown cause (46%), non-CFS chronic fatigue (35%), and healthy subjects (14%). Presyncope or syncope during tilt occurred in 38% of CFS patients, 21% of patients with non-CFS chronic fatigue, and 43% of patients with recurrent syncope. The average HIS values were: CFS = +2.02, non-CFS chronic fatigue = -2.89, syncope = -3.2, healthy = -2.48. The odds ratios for CFS patients to have HIS > -0.98 was 8.8 compared with non-CFS chronic fatigue patients, 14.6 compared with recurrent syncope patients, and 34.8 compared to healthy controls.
CONCLUSION: The cardiovascular reactivity in patients with CFS has certain features in common with the reactivity in patients with recurrent syncope or non-CFS chronic fatigue, such as the frequent occurrence of vasodepressor reaction, cardioinhibitory reaction, and postural tachycardia syndrome. Apart from to these shared responses, the large majority of CFS patients exhibit a particular abnormality which is characterized by HIS values > -0.98. Thus, HIS > -0.98 lends objective criteria to the assessment of CFS.
See also Naschitz et al. Journal of Hypertension, 2003, 17, 111-118.
Nijs, J., Demanet, C., McGregor, NR., De Becker, P., Verhas, M., Englebienne, P and De Meirleir, K. Monitoring a hypothetical channelopathy in chronic fatigue syndrome: preliminary observations. Journal of Chronic Fatigue Syndrome, 2003, 11, 1, 117-133.
Small study (27 people with CFS [CDC criteria ‘94], 20 controls). Abnormalities were found in whole body potassium content (50% of patients), and there were some abnormalities on immunophenotyping. Results suggest that a channelopathy exists in a subset of patients.
Nijs, J., De Meirleir, K., Englebienne, P and McGregor, N. Chronic fatigue syndrome: a risk factor for osteopenia? Medical Hypotheses, 2003, 60, 1, 65-68.
No data documenting a possible depletion of bone mineral density in patients with CFS are currently available. However, recent pathophysiological observations in CFS patients may have deleterious consequences on bone density. Firstly, the deregulation of the 2,5A synthetase RNase L antiviral pathway and its associated channelopathy, implicates increased demands for calcium and consequent increased calcium reabsorption from the skeletal system. Secondly, Mycoplasma fermentans which has been frequently associated with CFS, produces a lipopeptide, named 2-kDa macrophage-activating lipopeptide (MALP-2), which stimulates macrophages. MALP-2 has been shown to enhance bone resorption in a dose-dependent manner, at least in part by stimulating the formation of prostaglandins. Thirdly, decreased levels of insulin-like growth factor I (IGF-I) have been reported in CFS-patients. IGF-I is critical to the proliferation of osteoblasts. Consequently, depleted levels of IGF-I may shift the balance between osteoclastic and osteoblastic activity towards bone resorption.
Olson, LG., Ambrogetti, A and Sutherland, DC. A pilot randomized controlled trial of dexamphetamine in patients with chronic fatigue syndrome. Psychosomatics, 2003, 44, 1, 38-43.
This study determined whether dexamphetamine improved symptoms and quality of life in patients with CFS. The setting was a specialized clinic within a tertiary referral hospital. This was a 6‑week parallel-group, placebo-controlled trial with random allocation.
There was a 2-week dose-adjustment phase and a 4-week stable treatment period. Outcome measures were the Fatigue Severity Scale, the Medical Outcomes Study 36-item Short-Form Health Survey, and two patient-determined outcomes. Ten patients were randomly assigned to dexamphetamine, and 10 were assigned to placebo. Fatigue Severity Scale scores improved in nine of 10 dexamphetamine and four of 10 placebo patients. The change in mean score was statistically significant. There were large but statistically nonsignificant changes in scores for the Short-Form Health Survey domains vitality and physical functioning.
Dexamphetamine may be useful in the management of CFS; a larger and longer trial is justified by these results.
Peres, M., Zukerman, E., Young, W and Silberstein, S. Fatigue in chronic migraine patients. Cephalalgia, 2002, 22, 9, 720-724.
Fatigue is a common symptom frequently reported in many disorders including headaches, but little is known about its nature. The objective was to determine the prevalence of fatigue in chronic migraine (CM) patients, to define its subtypes and its relationship with other conditions comorbid with CM.
Sixty-three CM patients were analysed. The Fatigue Severity Scale (FSS), the Chalder fatigue scale and the CDC diagnostic criteria for CFS were used. Fifty-three (84.1%) patients had FSS scores greater than 27. Forty-two (66.7%) patients met the CDC criteria for CFS. Thirty-two patients (50.8%) met the modified CDC criteria (without headache).
Beck depression scores correlated with FSS, mental and physical fatigue scores. Trait anxiety scores also correlated with fatigue scales. Women had higher FSS scores than men, p<0.05. Physical fatigue was associated with fibromyalgia, p<0.05. Fatigue as a symptom and CFS as a disorder are both common in CM patients.
Therapeutic interventions include a graded aerobic exercise program, CBT and antidepressants. Identification of fatigue and its subtypes in headache disorders and recognition of headaches in CFS patients has implications for the pathophysiology, diagnosis and treatment of these disorders.
Shee, CD. Phantom lymphadenopathy. An association with chronic fatigue syndrome. Postgraduate Medical Journal, 2003, 79, 927, 59-60.
Ten patients with self-diagnosed enlarged lymph glands who were referred to a medical out-patient clinic were found to have chronic fatigue and other symptoms, fulfilling the CDC criteria. Lymphadenopathy was not confirmed.
Shephard, RJ. Cytokine responses to physical activity, with particular reference to IL-6: sources, actions, and clinical implications. Critical Reviews in Immunology, 2002, 22, 3, 165-182.
The present review examines the cytokine response to acute exercise stress, with particular emphasis on the balance between pro-inflammatory and anti-inflammatory mechanisms, and the release of IL-6. Prolonged endurance exercise induces a sequenced release of pro- and anti-inflammatory cytokines, and IL-6 plays a dominant role. The magnitude of this response bears a general relationship to the intensity of effort, but the duration of activity and many environmental factors also modulate cytokine release.
Although many types of cells are capable of producing cytokines, the main source of the exercise-induced IL-6 production appears to be the exercising muscle. The primary function of the additional IL-6 may be to regulate the supply of carbohydrate as muscle reserves of glycogen become depleted. There is also a delayed release of cytokines following eccentric exercise that is related to the repair of muscle injury. Since the production of cytokines is greater with endurance than with resistance exercise, it seems unlikely that they play an important role in the hypertrophy of muscle and bone.
More research is needed on a number of important clinical issues where the exercise-induced release of cytokines may have relevance. Exercise-induced cytokine secretion has the potential to provide a simple model of sepsis. Preliminary observations suggest it may also modulate the risk of type 2 diabetes mellitus. Cytokine concentrations are increased in CFS, although it is less clear that the cytokine secretion is responsible for fatigue in humans.
Exercise-induced modulations in cytokine secretion may contribute to allergies, bronchospasm, and upper respiratory infections in the endurance athlete. Further, the cytokine cascade is involved in the process of atherogenesis, and exercise-induced changes in cytokine production may expose latent HIV to chemotherapeutic agents.
Simpson, LO. On the pathophysiology of ME\CFS. New Zealand Family Physician, 2002, 29, 426-428.
Fascinating article on ME focusing on the evidence linking the illness with red cell shape.
See also other articles in the same issue, particularly Murdoch C, on the disbelief surrounding ME (p. 383-384).
Stein, E. Chronic fatigue syndrome: A biological approach. Canadian Journal of Psychiatry, 2002, 47, 9, 881-882.
Yamamoto, Y., La Manca, JJ and Natelson, BH. A measure of heart rate variability is sensitive to orthostatic challenge in women with chronic fatigue syndrome. Experimental Biology & Medicine, 2003, 228, 2, 167-174.
Data from 24 women with CFS and 22 healthy, sedentary controls suggest that a decrease in aperiodic fractal component of heart rate variability in response to HUT can be used to differentiate patients with CFS from controls.
Vecchiet, J., Cipollone, F., Falasca, K., Mezzetti, A., Pizzigallo, E., Bucciarelli, T., De Laurentis, S., Affaitati, G., De Cesare, D and Giamberardino, MA. Relationship between musculoskeletal symptoms and blood markers of oxidative stress in patients with chronic fatigue syndrome. Neuroscience Letters, 2003, 335, 3, 151-154.
In 21 patients with CFS versus 20 normal subjects, we investigated the oxidant/antioxidant balance and its correlation with muscle symptoms.
Patients versus controls showed significantly: lower Lag Phase and Vitamin E (Vit E) concentrations in plasma and low-density lipoproteins (LDL), higher LDL thiobarbituric acid reactive substances (TBARS), higher fatigue and lower muscle pain thresholds to electrical stimulation. A significant direct linear correlation was found between fatigue and TBARS, thresholds and Lag Phase, thresholds and Vit E in plasma and LDL. A significant inverse linear correlation was found between fatigue and Lag Phase, fatigue and Vit E, thresholds and TBARS.
Increased oxidative stress and decreased antioxidant defenses are related to the extent of symptomatology in CFS, suggesting that antioxidant supplementation might relieve muscle symptoms in the syndrome.
Williams, G., Waterhouse, J., Mugarza, J., Minors, D and Hayden, K. Therapy of circadian rhythm disorders in chronic fatigue syndrome: no symptpomatic improvement with melatonin or phytotherapy. European Journal of Clinical Investigation, 2002, 32, 11, 831-837.
Study of 30 patients with "unexplained fatigue" who were given 5 mg melatonin and phytotherapy (2500 Lux for one hour am), each for 12 weeks. There was no significant effect on symptoms, or other measures (e.g. MOS-SF).
Carruthers, BM., Jain, AK., De Meirleir, KL., Peterson, DL., Klimas, NG., Lerner, AM., Bested, AC., Flor-Henry, P., Joshi, P., Powles, ACP., Sherkey, JA and van de Sande, MI. Myalgic encephalomyelitis/chronic fatigue syndrome: clinical working case definition, diagnostic and treatment protocols. Journal of Chronic Fatigue Syndrome, 2003, 11, 1, 7-126.
ABSTRACT: Recent years have brought growing recognition of the need for clinical criteria for myalgic encephalomyelitis (ME), which is also called CFS. An Expert Subcommittee of Health Canada established the Terms of Reference, and selected an Expert Medical Consensus Panel representing treating physicians, teaching faculty and researchers. A Consensus Workshop was held on March 30 to April 1, 2001 to culminate the review process and establish consensus for a clinical working case definition, diagnostic protocols and treatment protocols. We present a systematic clinical working case definition that encourages a diagnosis based on characteristic patterns of symptom clusters, which reflect specific areas of pathogenesis. Diagnostic and treatment protocols, and a short overview of research are given to facilitate a comprehensive and integrated approach to this illness. Throughout this paper, 'myalgic encephalomyelitis' and 'chronic fatigue syndrome' are used interchangeably and this illness is referred to as 'ME/CFS'.
EXTRACTS: A patient with ME/CFS will meet the criteria for fatigue, post-exertional malaise and/or fatigue, sleep dysfunction, and pain; have two or more neurological/cognitive manifestations and one or more symptoms from two of the categories of autonomic, neuroendocrine and immune manifestations; and adhere to item 7.
1. Fatigue: The patient must have a significant degree of new onset, unexplained, persistent, or recurrent physical and mental fatigue that substantially reduces activity level.
2. Post-Exertional Malaise and/or Fatigue: There is an inappropriate loss of physical and mental stamina, rapid muscular and cognitive fatigability, post exertional malaise and/or fatigue and/or pain and a tendency for other associated symptoms within the patient's cluster of symptoms to worsen. There is a pathologically slow recovery period - usually 24 hours or longer.
3. Sleep Dysfunction:* There is unrefreshed sleep or sleep quantity or rhythm disturbances such as reversed or chaotic diurnal sleep rhythms.
4. Pain:* There is a significant degree of myalgia. Pain can be experienced in the muscles and/or joints, and is often widespread and migratory in nature. Often there are significant headaches of new type, pattern or severity.
5. Neurological/Cognitive Manifestations: Two or more of the following difficulties should be present: confusion, impairment of concentration and short-term memory consolidation, disorientation, difficulty with information processing, categorizing and word retrieval, and perceptual and sensory disturbances - e.g., spatial instability and disorientation and inability to focus vision. Ataxia, muscle weakness and fasciculations are common. There may be overload phenomena: cognitive,sensory - e.g., photophobia and hypersensitivity to noise - and/or emotional overload, which may lead to "crash" periods and/or anxiety.
6. At least one symptom from two of the following categories:
a. Autonomic manifestations: orthostatic intolerance-neurally mediated hypotenstion (NMH), postural orthostatic tachycardia syndrome (POTS), delayed postural hypotension; light‑headedness; extreme pallor; nausea and irritable bowel syndrome; urinary frequency and bladder dysfunction; palpitations with or without cardiac arrhythmias; exertional dyspnea.
b. Neuroendocrine manifestations: loss of thermostatic stability - subnormal body temperature and marked diurnal fluctuation, sweating episodes, recurrent feelings of feverishness and cold extremities; intolerance of extremes of heat and cold; marked weight change - anorexia or abnormal appetite; loss of adaptability and worsening of symptoms with stress.
c. Immune manifestations: tender lymph nodes, recurrent sore throat, recurrent flu-like symptoms, general malaise, new sensitivities to food, medications and/or chemicals.
7. The illness persists for at least six months. It usually has a distinct onset,** although it may be gradual. Preliminary diagnosis may be possible earlier. Three months is appropriate for children. To be included, the symptoms must have begun or have been significantly altered after the onset of this illness. It is unlikely that a patient will suffer from all symptoms in criteria 5 and 6. The disturbances tend to form symptom clusters that may fluctuate and change over time. Children often have numerous prominent symptoms but their order of severity tends to vary from day to day.
*There is a small number of patients who have no pain or sleep dysfunction, but no other diagnosis fits except ME/CFS. A diagnosis of ME/CFS can be entertained when this group has an infectious illness type onset.
**Some patients have been unhealthy for other reasons prior to the onset of ME/CFS and lack detectable triggers at onset and/or have more gradual or insidious onset.
The article also gives guidance on exclusions, tests and management. This is supplemented by a section on the research. The following is included in the section on CBT.
"The question arises whether a formal CBT or GET program adds anything to what is available in the ordinary medical setting. A well informed physician empowers the patient by respecting their experiences, counsels the patients in coping strategies, and helps them achieve optimal exercise and activity levels within their limits in a common sense, non-ideological manner, which is not tied to deadlines or other hidden agenda.
Physicians must take as much care in prescribing appropriate exercise as in prescribing medications to ME/CFS patients. Attending physicians should only approve of exercise programs in which the patient's autonomy is respected, appropriate pacing is encouraged, fluctuations in severity of symptoms are taken into account, and adequate rest periods are incorporated. Patients should be monitored frequently but unobtrusively for signs of relapse."
[Ed. note: The approach to CBT is noticeably more objective than any other review published in recent years. It makes this a most significant document. On the hypothesis underlying CBT/GET:
"To ignore the demonstrated biological pathology of this illness, to disregard the patient's autonomy and experience and tell them to ignore their symptoms, all too often leads to blaming patients for their illness and withholding medical support and treatment."
This description of the illness resembles ME more than any other recent account of CFS.]
See also editorial. Ibid, p 1-6.
Chalder, T, Godfrey, E., Ridsdale, L., King, M and Wessely, S. Psychological treatment for chronic fatigue in primary care. Results from a randomized controlled trial - predictors of outcome and mechanisms of change. Proceedings from the British Psychological Society, 2003, 11, 1, 16.
Abstract. Patients were given six sessions of CBT and counselling at local surgeries. All had reported chronic fatigue for three months or more (n=160).
There were no group differences in terms of effect. Factors associated with good outcome included less disability at assessment, a psychological illness attribution, and the belief that the consequences of fatigue were relatively minor.
Marmion, BP., Harris, RJ., Storm, PA and Semendric, L. Q fever: still a mysterious disease. Quarterly Journal of Medicine, 2002, 95, 832-833.
Letter responding to an editorial (ibid 491). See also Wildman MJ and Ayres, JG (ibid 833-834).
Peters, S., Stanley, I., Rose, M., Kaney, S and Salmon, P. A randomized controlled trial of group aerobic exercise in primary care patients with persistent, unexplained physical symptoms. Family Practice, 2002, 19, 6, 665-674.
BACKGROUND: The management of persistent, unexplained physical symptoms is challenging and often unsatisfactory for patients and doctors. Aerobic exercise training has benefited patients referred to secondary care with symptoms of chronic fatigue and fibromyalgia. It is not known if this approach is either possible or beneficial for patients with the broader range of persistent, unexplained symptoms found in primary care.
OBJECTIVES: To examine the feasibility and effects of aerobic exercise training in primary care patients with unexplained physical symptoms persisting more than 12 months.
METHODS: Randomized comparison (n=228) of aerobic exercise with stretching as control among patients recruited from primary care. Training comprised 20, one-hour, sessions led by NHS physiotherapists. Adherence to training was recorded along with two groups of outcome measures: (i) documented symptoms and health care use, monitored from six months before to six months after training; and (ii) self-reported measures including emotional state and perceived disability, assessed before, during and six months after training.
RESULTS: Exercise training proved feasible: more than 70% of referred patients attended for assessment and were randomized to aerobic or control exercise; 78% of eligible patients attended the first session; and median attendance was 11 sessions for both programmes. Primary care consultations and prescriptions were significantly reduced in the 6 months after training; extent of reduction was related to attendance at training sessions, irrespective of type. Whilst self-reported measures improved similarly during both training programmes, improvements were unrelated to level of attendance.
CONCLUSION: For primary care patients with persistent, unexplained physical symptoms willing to be involved in exercise training, aerobic exercise offers no benefits over non‑aerobic exercise. Whilst the observed reduction in primary health care use following exercise training is potentially of practical importance in a group of patients characterized by high consultation rates, improvement in patients' subjective state was not clearly attributable to exercise training.
Patarca-Montero, R. Chronic Fatigue Syndrome and the Body's Immune Defense System. NJ: Haworth Press. 2002. Pb. 122pp.
Concise review focusing on CFS and immunology.
Patarca-Montero, R. The Concise Encyclopedia of Fibromyalgia and Myofascial Pain. NJ: Haworth Press. 2002. Pb. 201pp.
Useful guide.
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