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Volume 1, Number 4 |
1st December 1998 |
Borish, L., Schmaling, K., DiClementi, JD., Streib, J., Negri, J and Jones, JF. Chronic fatigue syndrome: Identification of distinct subgroups on the basis of allergy and psychologic variables. Journal of Allergy and Clinical Immunology, 1998, 102, 2, 222-230.
Studies were performed on 18 patients with acute-onset CFS (CDC criteria '88, no premorbid psychiatric disorder, 15 were atopic), and control cohorts consisting of healthy subjects (n=11), allergic subjects (n=14), and individuals with primary depression (n=12: 7 out 10 tested were atopic). Psychological evaluations included administration of the Diagnostic Interview Schedule (DIS), the Structured Clinical Interview (SCID-II), and the Symptom Checklist-90-Revised (SCL-90-R).
Increases in tumor necrosis factor (TNF)-a were identified in individual subjects with CFS and allergic subjects in comparison with healthy controls (p<.01 and p<.05, respectively). Similar trends were observed for interferon (IFN)-a in allergic subjects and patients with CFS compared with normal controls. In contrast to these proinflammatory cytokines, both patients with CFS and allergic subjects showed a statistically significant (p<.01) decrease in IL-10 concentrations compared with healthy controls.
The seasonal exacerbation of allergy was associated with a further increase in cellular IFN-a but no further modulation of TNF-a or IL-10. Similarly, self-reported exacerbations of CFS were associated with a further increase in IFN-a and occurred at times of seasonal exposures to allergens. This linkage does not permit making any definitive conclusions regarding a causative influence of either seasonal allergies or the increase in cellular IFN-a with the increase in CFS symptoms. Psychological variables were predictive of immune status within the CFS sample (p<.05). Specifically, the absence of a personality disorder but greater endorsement of global psychiatric symptoms was predictive of immune activation. Conversely, as IFN-a increased during the allergy season, the severity of their psychological symptoms diminished.
Most of the subjects with CFS were allergic, and the CFS and allergy cohorts were similar in terms of their immune status. However, the CFS patients could be discriminated by the distinct psychological profiles among subjects with and without immune activation. The researchers speculate that in a large subgroup of subjects with CFS who have allergies, the concomitant influences of immune activation brought on by allergic inflammation in an individual with the appropriate psychological profile may interact to produce the symptoms of CFS.
[Ed. note: The theory about psychological vulnerability is inconsistent with the lack of premorbid psychiatric illness in the patients. The link between psychological symptoms and immune activation is a statistical relationship, not necessarily a causal one. The opposite of the suggested association should also be considered, i.e. allergic symptoms could have predisposed patients to develop psychological distress. The authors did not discuss whether the theory also applies to CFS patients who are not allergic.]
Cannon, JG., Angel, JB., Abad, LW., O'Grady, J., Lundgren, N., Fagioli, L and Komaroff, AL. Hormonal influences on stress-induced neutrophil mobilization in health and chronic fatigue syndrome. Journal of Clinical Immunology, 1998, 18, 4, 291-298.
This investigation tested the hypothesis that 8 women diagnosed with acute onset, post-infectious CFS (CDC criteria '88 plus post-exertional malaise) would exhibit significantly greater systemic indices of exercise-induced leukocyte mobilization and inflammation (neutrophilia, lactoferrin release, complement activation) than controls matched for age, weight, and habitual activity. Subjects stepped up and down on a platform adjusted to the height of the patella for 15 min, paced by metronome. Blood samples were collected the day before exercise and following exercise for determination of circulating neutrophils and plasma concentrations of lactoferrin, C3a des arg, and creatine kinase. Complete 24-hr urine collections were made for determination of cortisol excretion.
For all subjects, circulating neutrophil counts increased 33% and lactoferrin increased 27% after exercise, whereas plasma C3a des arg and creatine kinase did not increase. There was no difference between the groups. In healthy women, circulating neutrophil numbers exhibited previously described relationships with physiological variables: basal neutrophil counts correlated with plasma progesterone concentrations and the exercise-induced neutrophilia correlated with both urinary cortisol and plasma creatine kinase concentrations. However, these relationships were not observed in the people with CFS.
"These results suggest that normal endocrine influences on the circulating neutrophil pool may be disrupted in patients with CFS".
Levine, PH., Whiteside, TL., Friberg, D., Bryant, J., Colclough, G and Herberman, RB. Dysfunction of natural killer activity in a family with chronic fatigue syndrome. Clinical Immunology and Immunopathology, 1998, 88, 1, 96-104.
A family was identified with 5 of 6 siblings and 3 other immediate family members who had developed CFS (CDC criteria '88 and '94) as adults. Sixty-eight blood samples were obtained over a period of 2 years from 20 family members (8 affected, 12 unaffected) and 8 normal controls. All blood samples were tested for NK activity and for the number of circulating CD3-CD56+ and CD3-CD16+.
The NK activity of the 8 affected immediate family members was significantly lower (p=0.006) than that of the concurrently tested normal controls. The results for unaffected family members were intermediate between these two groups, and there was no significant difference between the unaffected family members and cases. No differences were seen between the three groups in terms of the absolute number of CD3-CD56+ or CD3-CD16+ lymphocytes in the peripheral blood.
Familial CFS was associated with persistently low NK activity, which was documented in 6/8 cases and in 4/12 unaffected family members. In the family with 5 of 6 siblings who had documented CFS, 2 of their offspring had paediatric malignancies. There was also a lower CD4+/CD8+ ratio in the patients with CFS and their families compared to the normal controls. This could be attributed to the higher absolute number of CD8+ cells.
"Low NK activity in this family may be a result of a genetically determined immunologic abnormality predisposing to CFS and cancer."
Richardson, J and Costa, DC. Relationship between SPECT scans and buspirone tests in patients with ME/CFS. Journal of Chronic Fatigue Syndrome, 1998, 4, 3, 23-38.
This study involved 39 patients with CFS (Oxford and CDC criteria) who also met criteria for ME/CFS. Three suffered from epilepsy and some were recovering from their fatigue syndrome. None had a psychiatric disorder. Tests included SPECT plus cortisol and prolactin studies after buspirone.
There were greater rises in prolactin levels in the CFS patients compared to the controls (details published elsewhere). The SPECT scans revealed that all patients had hypoperfusion in some area of the brain; 62% in the brain stem and 51% in the caudate nuclei. There was no hypoperfusion in the visual cortical areas.
According to the researchers, the findings provide "actual evidence of neurological dysfunction".
Tirelli, U., Chierichetti, F., Tavio, M., Simonelli, C., Bianchin, G., Zanco, P and Ferlin, G. Brain positron emission tomography (PET) in chronic fatigue syndrome: preliminary data. American Journal of Medicine, 1998, 105, 3A, 54s-58s.
In this article, the researchers describe the results from high resolution PET scans on 18 patients with CFS (CDC criteria), 6 patients with major depression (drug free) and 6 healthy controls. None of the CFS patients had a psychiatric disorder and none were taking any medication at the time of testing.
The PET images examined 22 cortical and subcortical areas. PET is better than SPECT at detecting small structures such as the brain stem.
The scans revealed significantly reduced glucose metabolism in the brainstem of patients with CFS compared with the depressed (p<.009) and healthy controls (p<.013). The area particularly affected in the brainstem was the pons. There was also significant hypometabolism in the right mediofrontal cortex in the CFS group compared with the healthy controls (p<.010).
This research is consistent with the findings of Costa et al (QJM, 1995, 88, 767) using SPECT. The hypometabolism of the brainstem has not been documented in any psychiatric disorder assessed to date.
Castell, LM., Phoenix, J., Edwards, RHT and Newsholme, EA. Plasma amino acid measurement in exercise-related chronic fatigue syndrome. Journal of Physiology, 1998, 509 (SP ISS), 206.
This short article reports on plasma concentrations of free tryptophan, branched chain amino-acids (BCAA) and the ratio of free tryptophan/BCAA before, during and after exercise (on a bicycle ergometer). Subjects were 10 patients with CFS (not defined) and 10 sedentary, age and gender matched controls. No patient took anti-depressants.
The main findings were that baseline free tryptophan levels were higher in patients than in controls (p<.05) but that the increase in those levels during and immediately after exercise in the controls was not seen in patients. There were no changes in plasma BCAA levels in either group. Finally, the plasma concentration ratio of tryptophan/BCAA was 31% higher in the patients compared with the controls and did not change during exercise.
"This, together with the abnormally high baseline level of free tryptophan in the CFS patients, might indicate increased levels of 5-HT leading to fatigue at rest. Alternatively, any involvement of the serotonergic system in chronic fatigue may be in terms of increased brain 5-HT receptor sensitivity, such as that observed by Cleare et al" (J. Affect. Disord, 1995, 35, 283).
De Lorenzo, F., Xiao, H., Mukherjee, M., Harcup, J., Suleiman, S., Kadziola, Z and Kakkar, VV. Chronic fatigue syndrome: physical and cardiovascular deconditioning. Quarterly Journal of Medicine, 1998, 91, 7, 475-481.
The researchers investigated physical and/or cardiovascular deconditioning in 273 CFS patients (CDC criteria '88) and 72 healthy controls. They used laboratory tests to assess haematological, biochemical, endocrinological and immunological systems. The cardiovascular system was assessed by echocardiography and carotid echography. Body composition was determined by dual energy X-ray absorptiometry (DEXA).
CFS patients had smaller left ventricular end systolic (p<0.001) and diastolic (p=0.008) dimensions but thinner posterior walls (p=0.02) than corresponding values in healthy controls. Left ventricular mass was also reduced in CFS patients (p=0.006). Both the maximum (p<0.001) and minimum (p<0.008) diameter of the carotid artery were smaller in CFS patients. The laboratory screening tests showed significant differences in serum albumin (p=0.05), phosphate (lower in CFS, p= 0.02), HDL-cholesterol (p=0.03), HDL: total cholesterol ratio (p=0.01), triglycerides (p=0.02), neutrophils (increased in CFS, p=0.01) and thyroid-stimulating hormone (p=0.04) between CFS patients and controls. Male CFS patients had an increased percentage of fat mass compared with healthy male subjects (p=0.02).
"This large group of CFS patients had evidence of physical and cardiovascular deconditioning". However, whether fatigue is related to this or to an altered sympathetic-parasympathetic balance as previously reported, remains unclear.
Kuratsune, H., Yamaguti, K., Lindh, G., Evengard, B., Takahashi, M., Machii, T., Matsumura, K., Takaishi, J., Kawata, S., Langstrom, B., Kanakura, Y., Kitani, T., Watanabe, Y. Low levels of serum acylcarnitine in chronic fatigue syndrome and chronic hepatitis type C, but not seen in other diseases. International Journal of Molecular Medicine, 1998, 2, 1, 51-56.
A study of 57 Swedish women with CFS (CDC criteria '88 or '94) found significantly lower serum acylcarnitine (ACR) compared to 46 healthy controls (p<0.001). Most patients had the deficiency, which was also found previously in Japanese patients and in people with chronic hepatitis C. However, it was not present in other medically ill populations such as patients with haematological malignancies, chronic pancreatitis, hypertension and diabetes. However, some people with psychiatric disorders also showed reduced serum ACR, although the mean values were not significantly different from those of the controls.
These findings indicate that serum ACR deficiency may be a characteristic of people with CFS and that it is not a local phenomenon peculiar to the Japanese. Recently, the researchers studied the ACR uptake into the brain and found this was lower in the anterior cingulate and dorsal prefrontal cortices of the CFS group (n=8) compared to the healthy controls (n=8). These regions are thought to be related to mood and the deficiency may therefore explain some of the neuropsychiatric symptoms of CFS.
ACR may have an effect as an antioxidant and be linked to the production of cytokines.
Kuratsune, H., Yamaguti, K., Sawada, M., Kodate, S., Machii, T., Kanakura, Y and Kitani, T. Dehydroepiandrosterone sulfate deficiency in chronic fatigue syndrome. International Journal of Molecular Medicine, 1998, 1, 1, 143-146.
In order to study HPA axis and endocrine function, urine samples were collected from 49 patients with CFS and 35 healthy controls and blood samples were obtained from 17 female patients and 35 controls.
Levels of cortisol and ACTH were normal in both groups. However, the patients with CFS had lower levels of serum dehydroepiandrosterone sulfate (DHEA-S) compared with the controls (p<.001) and higher levels of androstenedione (p<.001). The DHEA-S deficiency was not related to age.
Serum DHEA-S is one of the most abundantly produced hormones which are secreted from the adrenal glands, and its physiological function is thought to be a precursor of sex steroids. DHEA-S has recently been shown to have physiological properties, such as neurosteroids, which are associated with such psychophysiological phenomena as memory, stress, anxiety, sleep and depression. Therefore, the deficiency of DHEA-S might be related to the neuropsychiatric symptoms in patients with CFS. Levels of DHEA-S were lower in those patients reporting cognitive impairment and depression.
[Ed. note: DHEA is an important immune system regulator. Since it is also produced in the skin (source: Loria), fresh air and sunshine may aid recovery.]
Lavietes, MH., Bergen, MT and Natelson, BH. Measurement of CO2 in chronic fatigue syndrome patients. Journal of Chronic Fatigue Syndrome, 1998, 4, 3, 3-11.
This study of 9 patients with CFS (modified CDC criteria) and 10 controls revealed no evidence of hyperventilation or abnormalities of respiratory regulation in the former. Results in both groups were affected by the way in which the data were collected (mouth-piece versus nasal cannula versus blood). Use of a mouthpiece appeared to stimulate ventilation and raise heart rate.
Rowbottom, DG., Keast, D., Green, S., Kakulas, B and Morton, AR. The case history of an elite ultra-endurance cyclist who developed chronic fatigue syndrome. Medicine and Science in Sports and Exercise, 1998, 30, 9, 1345-1348.
An elite ultra-endurance athlete who had previously undergone physiological and performance testing, developed CFS (Oxford criteria plus post-exertional fatigue). An incremental cycling exercise test conducted while he was suffering from CFS indicated decreases in the maximum workload achieved (W-max), the maximum oxygen uptake and the anaerobic threshold (AT) compared to pre-CFS data. A third test conducted after the athlete had shown indications of significant improvement in his clinical condition revealed yet further decreases in W-max and AT.
These data, along with submaximal exercise data and muscle biopsy electron microscopic analyses suggest that the performance decrements were the result of detraining, rather than an impairment of aerobic metabolism due to CFS per se. These data may be indicative of central, possibly neurological, factors influencing fatigue perception in CFS sufferers.
Blackwood, SK., MacHale, SM., Power, MJ., Goodwin, GM and Lawrie, SM. Effects of exercise on cognitive and motor function in chronic fatigue syndrome and depression. Journal of Neurology, Neurosurgery and Psychiatry, 1998, 65, 541-546.
This study compared the post-exercise cognitive and motor responses of 10 patients with CFS (CDC criteria '94), 10 patients with major depression and 10 healthy controls. Muscle strength was measured using a handgrip dynamometer and cognitive function tests assessed focused and sustained attention. Other measures included the Hospital Anxiety and Depression Scale (HAD), the MOS SF-36, heart rate, blood pressure, and questions regarding effort and fatigue. The cognitive tests were completed before and after a treadmill exercise test.
The results showed that the CFS group had higher ratings of perceived effort and fatigue during exercise than the depressed patients and controls, whereas the depressed group reported lower mood. After exertion, the CFS group showed a greater decrease than healthy controls on both focused and sustained attention tests, and greater deterioration than depressed patients on the focused attention test.
The findings indicate that patients with CFS "show a specific sensitivity to the effects of exertion on effortful cognitive functioning. This occurs despite subjective and objective evidence of effort allocation in CFS, suggesting that patients have reduced working memory capacity, or a greater demand to monitor cognitive processes, or both".
DeLuca, J., Johnson, SK., Ellis, SP and Natelson, BH. Sudden versus gradual onset of chronic fatigue syndrome differentiates individuals on cognitive and psychiatric measures. Journal of Psychiatric Research, 1997, 31, 1, 83-90.
This study assessed 36 patients with CFS (CDC criteria '88 and '92, moderate symptoms, no premorbid psychiatric disorders, duration <4 years) and 31 matched healthy sedentary controls. The patients were divided into those with a sudden onset (n=25) and those with a gradual onset (n=11). Measures included several cognitive tests, the Beck Depression Inventory (BDI) and a psychiatric interview (DIS).
The gradual onset group had a greater proportion of psychiatric disorders than the sudden onset patients (73% Vs 28%). Both groups showed a significant reduction in information processing ability relative to controls, but there was more memory impairment among the sudden onset group. There was no difference between the groups in terms of severity of fatigue and illness.
LaManca, JJ., Sisto, SA., DeLuca, J., Johnson, SK., Lange, G., Pareja, J., Cook, S and Natelson, BH. Influence of exhaustive treadmill exercise on cognitive functioning in chronic fatigue syndrome. American Journal of Medicine, 1998, 105, 3A, 59s-65s.
This study compared 19 patients with CFS (CDC criteria '88, '92 and '94 plus significant disability, no psychiatric disorders in the 5 years prior to illness, duration <6 years) and 20 sedentary controls on a number of cognitive tests before and after exercise to exhaustion.
The cognitive tests included measures assessing speed, vigilance, and attention. Other measures included the BDI, an IQ test (NAART) and ratings for fatigue and symptom severity. The cognitive test battery was completed before, immediately after and 24 hours after exercise on a treadmill to exhaustion.
There were no significant differences on the cognitive tests prior to exercise, no differences on the IQ test and no differences in terms of aerobic fitness levels between the groups. The CFS patients were more depressed but the mean (14.7) was suggestive of mild depression only. Post-exercise, there was no effect on accuracy, but on the tests assessing rapid naming and perceptual motor speed, the CFS group were significantly impaired. The patients also reported more fatigue.
The researchers conclude that after exercise, patients with CFS demonstrated impairment in terms of the speed of information processing, though not attention. The impairment was maintained at 24 hours post-exercise.
Michiels, V., Cluydts, R and Fischler, B. Attention and verbal learning in patients with Chronic Fatigue Syndrome. Journal of the International Neuropsychological Society, 1998, 4, 5, 456-466.
In this study, a battery of attentional tests and a verbal memory task were administered to 20 patients with CFS (Oxford criteria) and 22 healthy controls. The patients had a mean Karnofsky score of 73.3, 10% suffered from depression, 40% reported an infectious onset, 35% were taking antidepressants and 30% were taking benzodiazepines.
The patients performed more poorly on a span test measuring attentional capacity and working memory. Speeded attentional tasks with a more complex element of memory scanning and divided attention seemed to be a sensitive measure of reduced attentional capacity in these patients. Focused attention was not impaired. CFS patients were poorer on recall of verbal information across learning trials, and findings also suggest that poor performance on delayed recall might have been due to poor initial learning and not only to a retrieval failure. There was no relationship between performance and fatigue.
Morehouse, RL., Flanigan, M., MacDonald, DD., Braha, D and Shapiro, C. Depression and short REM latency in subjects with chronic fatigue syndrome. Psychosomatic Medicine, 1998, 60, 3, 347-351.
The hypothesized polysomnographic marker for depression, Rapid Eye Movement Latency (REML), was used to assess patients with CFS. REML is the time period between the onset of sleep and the onset of the first period of REM. People with CFS (modified CDC '88 criteria) were classified into depressed (n=21) and not depressed (n=20) groups using the DIS and were subsequently studied in a sleep laboratory for two nights.
Short REML showed a statistically significant correlation with the depressed state in CFS subjects. There was no excess of formal sleep disorders in this population.
Schmaling, KB., Hamilos, DL., DiClimenti, JD and Jones, JF. Pain perception in chronic fatigue syndrome. Journal of Chronic Fatigue syndrome, 1998, 4, 3, 13-22.
This study involved 15 women with CFS (CDC criteria '88, all acute onset, no premorbid psychiatric disorders), 11 people with major depression and 11 healthy controls. Pain perception was measured objectively by pressure dolorimeter and ice water cold pressor tests and subjectively with the McGill Pain Questionnaire (MPQ). Other measures included the MOS and SCL-90-R.
The CFS group reported lower levels of functioning on the MOS compared to the depressed patients and controls, lower health perception and more bodily pain. There was no difference between the three groups for pain threshold or intolerance levels although the CFS and depressed patients endorsed more pain symptoms than the controls on the MPQ.
Pain threshold or intolerance were not predicted by psychiatric symptoms or functional status. Contrary to predictions, CFS patients had a relatively greater pain tolerance than the other groups.
Vercoulen, JHMM., Bazelmans, E., Swanink, CMA., Galama, JMD., Fennis, JFM., van der Meer, JWM and Bleijenberg, G. Evaluating neuropsychological impairment in chronic fatigue syndrome. Journal of Clinical and Experimental Neuropsychology, 1998, 20, 2, 144-156.
This study compared the performance of 51 patients with CFS (Oxford criteria) and 53 healthy controls on battery of cognitive tests.
The results showed that only a minority of patients (29%) were impaired in neuropsychological functioning. There was no relationship between neuropsychological impairment on standardized tests and self-reported memory and concentration problems. Neuropsychological functioning was not related to fatigue or depression (BDI). There was a slower speed of information processing, which correlated with low levels of physical activity, though the researchers add that the two may be related because of a third variable. There was no association between focusing on somatic symptoms and performance on the tests.
[Ed. note: There is no information about subgroups. See DeLuca et al above].
Ware, NC. Sociosomatics and illness course in chronic fatigue syndrome. Psychosomatic Medicine, 1998, 60, 4, 394-401.
Sixty-six persons with CFS (CDC criteria '94) participated in a longitudinal study over 3 years. Measures included semistructured interviews, telephone interviews, and self-report questionnaires. The data presented came primarily from the Year 1 interviews.
CFS symptoms impeded performance at work and placed ill individuals at risk for job loss. Persons with CFS devised and implemented specific strategies to resist role constriction e.g. working flexible hours, passing as 'normal' and prioritising.
Hartz, AJ., Kuhn, EM and Levine, PH. Characteristics of fatigued persons associated with features of chronic fatigue syndrome. Journal of Chronic Fatigue Syndrome, 1998, 4, 3, 71-97.
In this study, the number and severity of symptoms, sudden onset and post-exertion fatigue were compared with other characteristics of the subjects.
The sample comprised 353 adults with chronic fatigue which had lasted at least 6 months and affected quality of life. They were recruited from a register of patients from a self-help group, clinics and CFS meetings. Questionnaires assessed the symptoms experienced, sleep problems, hours of fatigue after exercise, sudden onset, attitudes, depression, stress, counselling and a number of other variables. Among the patients, 29 had anaemia and 36 had thyroid disorders. Less than one third of the sample reported severe fatigue.
Fifty-seven per cent reported allergies, and nearly 60% had received counselling. There was a relationship in this population between CFS symptoms and frequent sinus or respiratory infections, but not with frequent colds. The number of CFS symptoms also correlated with muscle weakness (.59) and fever (.54). There was a positive association between sudden onset and symptoms of infection, the GI tract, number of CFS symptoms, post-exertional fatigue and sleep problems but no relationship between sudden onset and neurocognitive symptoms. Sudden onset was negatively correlated with depression, stress and sleep apnoea. A physical attribution was strongly associated with the number of CFS symptoms, post-exertional fatigue and a sudden onset. An attribution to stress or insufficient sleep was not associated with the number of CFS symptoms, sudden onset, or post-exertional fatigue.
The researchers suggest that symptoms such as fevers, chills, muscle weakness and sensitivity to alcohol could be added to the diagnostic criteria to help characterise persons with chronic fatigue. They also note that the findings do not provide evidence for a psychological basis of CFS features (other than neurocognitive disorders) but that they are consistent with a possible infectious or chronic low level immune activation basis in some people.
Jason, LA., Wagner, L., Rosenthal, S., Goodlatte, J., Lipkin, D., Papernik, M., Plioplys, S and Plioplys, AV. Estimating the prevalence of chronic fatigue syndrome among nurses. American Journal of Medicine, 1998, 105, 3A, 91s-93s.
A survey of two nurses associations found that 6% reported debilitating fatigue > 6 months. The medical records showed that 37 met the CDC criteria '94 for CFS. This suggests a prevalence rate of 1088 per 100,000.
Steele, L., Dobbins, JG., Fukuda, K., Reyes, M., Randall, B., Koppelman, M and Reeves, WC. The epidemiology of chronic fatigue in San Francisco. American Journal of Medicine, 1998, 105, 3A, 83s-90s.
A telephone survey among 8004 households in San Francisco revealed that 2% of the adult population suffered from a CFS-like illness. Since the patients were not clinically evaluated, this may not be an accurate assessment. There was a higher rate among African Americans, native Americans and persons engaged in clerical occupations; a lower rate among Asians. About 1.8% reported unexplained chronic fatigue but did not meet the CDC criteria ('94). These individuals tended to be less severely ill.
Marlin, RG., Anchel, H., Gibson, JC., Goldberg, WM and Swinton, M. An evaluation of multidisciplinary intervention for chronic fatigue syndrome with long-term follow-up, and a comparison with untreated controls. American Journal of Medicine, 1998, 105, 3A, 110s-114s.
This study compared 51 patients in a rehabilitation programme and 20 untreated controls. The groups were not randomised. Assessment included medical and psychological tests (e.g. MMPI, BDI, WAIS).
The programme focused on regulation of stimulant intake, sleep and stress management, treatment of psychopathology plus CBT and graded exercise independent of subjective state. Patients were seen for 1-4 hours at home, 2 or 3 times a week for 3-8 months. The outcome measure was the return to gainful employment.
All patients fulfilled the CDC criteria ('94) except for duration of symptoms (range 4-102 months in treated group). All were in receipt of disability benefits.
After treatment, 31 of the 51 treated patients (61%) had returned to work. Only 6 remained disabled. For the follow-up, 20 treated patients and 5 untreated ones were contacted an average of 33 months later. This revealed that the improvements were generally maintained.
[Ed. note: There are no details about concurrent psychopathology, severity of disability, type of onset, relationship to infection etc. There is no information about the percentage also taking psychotropic drugs, numbers with irrational beliefs, severity of residual symptoms if any etc.]
McKenzie, R., O'Fallon, A., Dale, J., Demitrack, M., Sharma, G., Deloria, M., Garcia Borreguero, D., Blackwelder, W and Straus, S. Low-dose hydrocortisone for treatment of chronic fatigue syndrome. A randomised controlled trial. Journal of the American Medical Association, 1998, 280, 12, 1061-1966.
A group of 56 patients with CFS (CDC criteria '88 and '94), completed a controlled trial of low-dose hydrocortisone (25-35 mg) or placebo for 12 weeks.
There were marked improvements recorded by the treatment group on the Wellness scale compared with the controls. However, there were no significant group differences on other measures, including the BDI, POMS, Hamilton Depression Rating Scale, SCL-90-R or Activity Scale. The side effects were generally mild. There was no correlation between cortisol levels and illness severity.
Although there was some improvement on hydrocortisone, the degree of adrenal suppression "precludes its practical use in CFS".
See also editorial by Streeten, DHP. The nature of chronic fatigue. Ibid, 1998, 280, 12, 1094-5.
Demitrack, MA. Chronic fatigue syndrome and fibromyalgia. Dilemmas in diagnosis and clinical management. Psychiatric Clinics of North America, 1998, 21, 3, 671-692.
Account of the literature, focusing with regard to CFS largely on findings supporting an older version of the CBT model.
Vollmer-Conna, U., Lloyd, A., Hickie, I and Wakefield, D. Chronic fatigue syndrome: an immunological perspective. Australian and New Zealand Journal of Psychiatry, 1998, 32, 4, 523-527.
Review focusing on the immunological aspects of CFS. The authors suggest that abnormal release of cytokines within the CNS may cause neural dysfunction by a variety of complex mechanisms. Neuropsychiatric symptoms in patients with CFS may be more closely related to disordered cytokine production by glial cells within the CNS than to circulating cytokines.
Wilke, WS., Fouad-Tarazi, FM., Cash, JM., Calabrese, LH. The connection between chronic fatigue syndrome and neurally mediated hypotension. Cleveland Clinic Journal of Medicine, 1998, 65, 5, 261-266.
Review of the early literature in neurally mediated hypotension and related conditions with advice regarding treatment.
Arzomand, ML. Chronic fatigue syndrome among school children and their special education needs. Journal of Chronic Fatigue Syndrome, 1998, 4, 3, 59-69.
One hundred and four questionnaire were sent out to paediatricians, child adolescent psychiatrists, parents of children with special needs and home tuition units, to identify the number of children with CFS attending junior or senior schools in the neighbouring boroughs of Sutton and Merton (UK). With a return rate of 53.8%, 22 children with CFS were identified, giving an overall point prevalence of 0.07%. Of the 22 cases, 21 were in one borough (Sutton). There were equal numbers of boys and girls.
The prevalence of CFS among the total population under 16 was estimated to be 0.03%. A significant number (63.6%) had received home tuition at some time during the illness. However, few doctors felt home tuition was necessary.
Bialy, GB., John, J., Kreugel, B., Malka, E., Ruddy, M and Preminger, M. Ambulatory BP monitoring and tilt table testing in chronic fatigue syndrome (Meeting Abstract). Journal of Hypertension, 1998, 16 (suppl. 2), S275.
A study of 23 patients with CFS (CDC criteria) found normal blood pressure in groups who tested positive (n=11) and negative (n=12) on tilt table testing. "These data do not suggest that perturbations in blood pressure contribute to CFS".
Borok, G. Chronic fatigue syndrome: an atopic state. Journal of Chronic Fatigue Syndrome, 1998, 4, 3, 39-57.
This article reports on the effect of using an elimination and rotation programme to identify reactions to foods. Patients were also advised to avoid inhalants such as perfumes.
The results in 234 patients with CFS (criteria unclear) showed that the majority reported an improvement in symptoms following the removal of offending foodstuffs. Tiredness was associated in 76% with the ingestion of refined carbohydrates to excess. Depression and emotional symptoms were relieved in 95% of those affected. The programme also helped the majority of those with irritable bowel syndrome. Petrol fumes and perfumes affected 18 patients. Salicylates affected 16 patients. 5% did not respond to the programme.
The author speculates that in a genetically predisposed group, food intolerance causes symptoms akin to both the major and minor criteria for CFS.
Caplan, C. Chronic fatigue syndrome or just plain tired? Canadian Medical Association Journal, 1998, 159, 5, 519-520.
Short guide for GPs.
See also Caplan, C. The search for a cause continues. Ibid, 539-540. Also Sibbald, B. Chronic fatigue syndrome comes out of the closet. Ibid, 537-541. Also Capen, K. Chronic fatigue syndrome gets court's nod of approval as legitimate disorder. Ibid, 533-534.
Corrado, G., Rea, P., Tinelli, F., Cavaliere, M., Pacchiarotti, C., Nardelli, F., Cardi, E and Riezzo, G. Normal electrical activity of the stomach in a patient with chronic fatigue syndrome. (Meeting Abstract). Gastroenterology, 1998, 114 (4 pt. 2, suppl), A737.
Case history of a 14 year old male with CFS, nausea and vomiting. Tests suggested that in CFS, gastric electrical activity is normal.
De Becker, P., Dendale, P., De Meirleir, K., Campine, I., Vandenborne, K and Hagers, Y. Autonomic testing in patients with chronic fatigue syndrome. American Journal of Medicine, 1998, 105, 3A, 22s-26s.
A study of 21 patients with CFS (CDC criteria '88) and 13 matched controls revealed no evidence of parasympathetic dysfunction though there was a sympathetic overactivity in patients after stress.
Delbanco, TL; Daley, J; Hartman, EE. A 56-year-old woman with chronic fatigue syndrome, 1 year later. Journal of the American Medical Association, 1998, 280, 4, 372.
Follow-up report on the woman with CFS described by Komaroff (ibid, 1997, 278, 1179). The patient made a significant recovery after 2 years of illness, but states "I'm not sure why". She notes more social support and changes in diet, medication (amitriptyline, helping sleep), massage and pacing.
Demitrack, MA and Crofford, LJ. Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic fatigue syndrome. Annals of the New York Academy of Sciences, 1998, 840, 684-697.
Discussion of evidence implicating HPA dysregulation in CFS and fibromyalgia, with emphasis on the research by Demitrack et al.
Dykman, KD., Tone, C., Ford, C and Dykman, RA. The effects of nutritional supplements on the symptoms of fibromyalgia and chronic fatigue syndrome. Integrative Physiological and Behavioral Science, 1998, 33, 1, 61-71.
A study of 25 patients with fibromyalgia, 12 with CFS (physician-diagnosed), and 13 people with both disorders, assessed the effect of a number of nutritional supplements on symptoms. A follow-up after nine months confirmed the benefits documented earlier. The majority noted improvements, particularly for symptoms such as fatigue, aches and pains and depression.
Findley, JC., Kerns, R., Weinberg, LD and Rosenberg, R. Self-efficacy as a psychological moderator of chronic fatigue syndrome. Journal of Behavioral Medicine, 1998, 21, 4, 351-362.
A study of 68 patients with CFS recruited from a support group found that low self-efficacy was related to more intense symptoms, disability and distress. Self-efficacy refers to the confidence that one can execute a behaviour required to produce outcomes.
Franklin, A. How I manage chronic fatigue syndrome. Archives of Disease in Childhood, 1998, 79, 4, 375-378.
An account of CFS in children by an experienced paediatrician.
Goudsmit, E. Treating chronic fatigue with exercise. British Medical Journal, 1998, 317, 599.
Letter challenging editorial by Sharpe and Wessely (ibid, 1998, 316, 796). Goudsmit notes that "CFS is now generally acknowledged to be a heterogeneous condition... what may suit one person, may be totally inappropriate for another. As research has shown, most patients with CFS remain ambulant, spend relatively few daytime hours resting, they are no more inactive than people with mild multiple sclerosis and tend to perform at or near their activity ceiling. What these patients need is not a strict programme where rest is pencilled in according to a predetermined plan, but a flexible approach which does not ignore current energy levels or make people feel guilty if they increase rest periods when they consider this to be right for them."
From a theoretical perspective, she comments that inactivity may well be an important factor in CFS, but that the authors did not provide a single reference to back their claim that many patients resort to "excessive rest". She asks if the theory of 'excessive inactivity' as a perpetuator of CFS is largely based on anecdotal reports and articles in magazines.
Goudsmit adds: "For many years, CFS specialists have argued that the emphasis on fatigue is misleading and that theories relating to this illness must not just be able to explain the lack of energy but also the fluctuations in the disorder and such symptoms as cognitive dysfunction, intolerance to alcohol and sensitivities to certain drugs". She asks if Sharpe and Wessely believe that these are also the result of 'excessive rest'?
"I have no doubt that graded exercise helps many people with CFS, notably those who are mildly affected (as shown by measures such as the Karnofsky scale), yet spend long periods in bed. However, the chronically fatigued do not constitute a homogenous population and the claim that "rest has no place" in their treatment is not only overly simplistic but inconsistent with the available evidence. The question is not whether patients should rest but when."
See also letter by Baschetti (p. 600) on the heterogeneity of CFS, the difference between conditions according to the definitions used and the possible role of adrenal insufficiency.
Michael in his letter (p. 600) comments that exercise can improve mood and sleep in fatigue syndromes.
Sharpe and Wessely reply that there may well be subgroups. However, they believe that level of disability does not influence response to rehabilitation. They add that a reduction in reported activity is required by the CDC 1994 definition and that research regarding cortisol is inconclusive. They reiterate that they are not aware of evidence that supports prolonged rest or that contraindicates appropriate increases in activity.
[Ed. note: Critics of the view that CFS is a single entity have not subdivided patients according to severity of disability but on the basis of onset, pattern of symptoms and relationship with psychiatric disorders. The CDC 1994 criteria specify there must be a substantial reduction in activities, but research has shown that this rarely amounts to total avoidance, as described by Sharpe and Wessely. There is no controversy about appropriate increases in activity; the question is whether patients should continue to exercise if unwell, as Wessely recommends, or whether they can stop or reduce activity at such times.]
Harlow, BL., Signorello, LB., Hall, JE., Dailey, C and Komaroff, AL. Reproductive correlates of chronic fatigue syndrome. American Journal of Medicine, 1998, 105, 3A, 94s-99s.
A study of 150 women with CFS (CDC criteria '88) using questionnaires revealed increased prevalence of gynaecological disorders compared with 149 non-gynaecological, non-CFS controls. Women with CFS reported more irregular cycles, sporadic bleeding between periods, polycystic ovarian syndrome, hirsutism and ovarian cysts. The lower prevalence of pre-menstrual symptoms prior to the CFS indicates they do not have a general tendency to report symptoms and illness (as in somatisation).
The researchers suggest that a history of anovulation or oligo-ovulation may be a risk factor for CFS.
Johnson, SK. The biopsychosocial model and chronic fatigue syndrome. American Psychologist, 1998, 53, 1080-1081.
Letter commenting on an article by Jason et al (ibid, 1997, 52, 973). With reply by Jason (p. 1081-2), suggesting some degree of misunderstanding on Johnson's part.
Joyce, J., Rabe-Hesketh, S and Wessely, S. Reviewing the reviews. The example of chronic fatigue syndrome. Journal of the American Medical Association, 1998, 280, 3, 264-266.
Study of reviews concludes that citation of the literature is influenced by the authors' discipline and nationality.
Krilov, LR., Fisher, M., Friedman, SB., Reitman D and Mandel, FS. Course and outcome of chronic fatigue in children and adolescents. Pediatrics, 1998, 102, 2, 360-366.
During the summer of 1994, chart review was performed for the 58 patients evaluated between 1990 and 1994 and a telephone follow-up was conducted with 42 of the 58 families. Patients were predominantly female (71%) and white (94%), between 7 and 21 years (mean 14.6).
At time of presentation, 50% of patients had been fatigued for 1 to 6 months and 50% had been fatigued for 7 to 36 months. Sixty per cent indicated the fatigue had begun with an acute illness and 60% had a history of allergies. Most patients had a worsening of school performance and a decrease in social activities; 41% received home tutoring.
On follow-up, there was significant improvement in many patients: 43% of the families considered their child "cured", 52% considered their child "improved," whereas only 5% considered their child to be "the same." Statistical analyses demonstrated no demographic or clinical factors that distinguished those who did or did not do well on follow-up.
Natelson, BH., LaManca, JJ., Denny, TN., Vladutiu, A., Oleske, J., Hill, N., Bergen, MT., Korn, L and Hay, J. Immunologic parameters in chronic fatigue syndrome, major depression, and multiple sclerosis. American Journal of Medicine, 1998, 105, 3A, 43s-49s.
Seventy-one patients with CFS (CDC criteria '88 and '94, moderate or severe symptoms, duration <5 years, no premorbid psychopathology but only 30 without current psychiatric disorders) were compared with sedentary controls and patients with mild MS and major depression.
Of the 18 immunological parameters which were evaluated, the researchers only found reductions in the amount of serum IgG1 and IgG3 in the CFS group. The significance of these findings is unclear. There was no evidence of immune activation and there were no significant differences between patients with acute and gradual onset.
Terman, M., Levine, SM., Terman, JS and Doherty, S. Chronic fatigue syndrome and seasonal affective disorder: comorbidity, diagnostic overlap, and implications for treatment. American Journal of Medicine, 1998, 105, 3A, 115s-124s.
Study of 110 patients with CFS (CDC criteria '94, no premorbid major depression but not all with profound fatigue) revealed a subgroup whose symptoms showed seasonal variations (37%). The latter was strongly associated with depression. The overlap with SAD suggests that light therapy may help these patients.
American Journal of Medicine, 1998, 105, 3A. Recent developments in chronic fatigue syndrome. (Guest Ed: PH Levine).
Reviews and original research. Reviews include Levine (introduction to the subject), Lloyd (definitions, prevalence), Demitrack (neuroendocrine aspects), Rowe and Calkins (neurally mediated hypotension), Whiteside and Friberg (natural killer cell activity), Glaser and Kiecolt-Glaser (stress-associated immune modulation), Lange et al (neuroimaging), Bruno et al (parallels between post polio fatigue and CFS) and Sharpe (CBT).
Papers discussing original research are classified under subject.
Friedberg, F and Jason, LA. Understanding chronic fatigue syndrome. An empirical guide to assessment and treatment. Washington: APA. 1998. Hb. 266pp. £33.95.
Up-to-date introductory guide to CFS, focusing on assessment and rehabilitation. What makes it stand out from the other texts is that it's much more balanced and realistic, particularly in its description of the illness and its approach to treatment. For instance, while the authors accept that some patients may be fatigued due to phobic avoidance, they also acknowledge the cases where psychological problems play a lesser role. Moreover, Fred Friedberg's paced activity programme provides a well thought out and practical alternative to graded exercise, for the many patients whose main problem is not 'excessive rest'.
On the down side, I felt that the authors exaggerated the role of psychological factors and with the exception of the studies on avoidance and exercise, often overlooked important flaws in psychiatric research. Given their critical comments about the CBT model, I was somewhat surprised at their suggestion that their patients must differ from those in the UK. After all, one of the main arguments against the model has always been that it fails to acknowledge the existence of more sensible patients described both here and in the States.
Another criticism is the emphasis on cognitive-behavioural interventions as the basis for their programme. As someone who trained as a behaviour therapist, I tend to approach pure CFS\ME in the same way as cancer or MS. For example, telling people with cancer not to eat their favourite meal prior to chemotherapy may be a behavioural strategy but I'd rather class it under helpful advice or learning to cope. The same is true when one informs ME patients that they can conserve energy by varying the muscles used. Again, this is attempting to change behaviour, but does it also amount to CBT?
Personally, I prefer to describe the learning of coping skills to deal with the illness as part of a self-management programme, which also includes providing general information and emotional support. Why the reluctance to call it CBT? It's because I want to avoid pathologizing what may be characterised as normal, understandable responses to an extremely challenging situation. It's because I don't want to equate 'not knowing' the most sensible behaviours with disordered thinking associated with misleading information or psychiatric morbidity. The authors state elsewhere that the depression experienced by many CFS patients may be better described as demoralisation. Can't mental health professionals begin to differentiate between the various so-called 'maladaptive' beliefs to avoid further medicalization? Can we not restrict CBT for those who resist behaving sensibly, or who have truly irrational and unhelpful beliefs?
As I've noted many times before, I'm not anti-CBT and recognise its value for certain psychological problems. However, I'm still not convinced that there is as much psychopathology in this population as we are sometimes led to believe (e.g. by Ware and Kleinman, Surawy et al, Van Houdenhove et al etc.). Thus for sensible patients with no or little maladaptive behaviour, intervention may be restricted to providing information about the illness and 'helpful hints', basic emotional support and continued access to a knowledgeable professional. This approach is not far removed from what Friedberg and Jason advocate, but regretfully, they refer to the whole package as CBT.
Finally, a note about the discussion of the link with stress. In my view, it underestimates the damaging effects of the name (fatigue is not a description likely to elicit much sympathy), the lack of experts and the exaggeration of the psychiatric aspects in the literature. If people cope better with cancer, these may be the main reasons why.
Aside from these minor criticisms, I applaud the authors for not misrepresenting the experience of sufferers or the views of colleagues from other schools of thought. Moreover, the section on assessment and diagnosis is superb and contains information you won't find in other texts. Overall, I consider this the best and most practical book on the subject and recommend it as compulsory reading for all researchers and practitioners involved in the treatment of CFS. Buy it for yourself and get the library a copy too!
EMG
Bell, IR., Patarca, R., Baldwin, CM., Klimas, NG., Schwartz, GER and Hardin, EE. Serum neopterin and somatization in women with chemical intolerance, depressives, and normals. Neuropsychobiology, 1998, 38, 1, 13-18.
Serum neopterin, which has an inverse relationship with l-tryptophan availability, may offer a marker of inflammation and macrophage/monocyte activation. This study compared 14 women with chemical intolerance (CI) who had high levels of affective distress, 10 depressives without CI, and 11 healthy controls. The groups did not differ in terms of resting levels of serum neopterin. However, the CI group showed strong positive correlations between neopterin and all of the scales measuring somatization. These preliminary findings suggest the need for additional research on biological correlates of 'unexplained' multiple somatic symptoms in subtypes of apparent somatizing disorders.
Empson, M. Celiac disease or chronic fatigue syndrome? Can the current CDC working definition discriminate? American Journal of Medicine, 1998, 104, 79-80.
Case history of a 21 year old woman with a long history of lethargy and other symptoms consistent with CFS. She had low serum ferritin and borderline hypothyroidism when investigated by the author. A screening test for coeliac disease was performed using IgA endomysial Ab (positive) and IgA gliadin Ab (elevated). A small bowel biopsy confirmed a diagnosis of coeliac disease.
The author suggests that coeliac disease should be considered when assessing patients with chronic fatigue, especially if they report diarrhoea. Serum ferritin should be included in the investigation of those without gastrointestinal symptoms.
King, TS, Elia, M and Hunter, JO. Abnormal colonic fermentation in irritable bowel syndrome. Lancet, 1998, 352, 1187-1189.
This study found that the colonic gas production was greater in patients with irritable bowel syndrome than in controls. Both symptoms and gas production were reduced by an exclusion diet (no diary products or grains except rice, restrictions on yeast, citrus fruits, caffeinated drinks). The researchers suggest that the reductions may be associated with alterations in the activity of hydrogen-consuming bacteria and that fermentation may be an important factor in the pathogenesis of IBS.
Heijmans, M. Cognitive representations of chronic disease. An empirical study among patients with chronic fatigue syndrome and Addison's Disease. PhD. University of Utrecht, Holland. 1998.
This describes a number of studies which have been or will be published in journals. They underline the complexity of the psychological response to CFS, thus challenging the CBT model.
*The opinions expressed in the book review are the author's own and do not necessarily represent those of the editorial team.
This issue was compiled by Dr. E. Goudsmit, Dr. A. Macintyre and Mrs S. Howes. We gratefully acknowledge the help and support from Dr. C. Shepherd and Mr. D. Axford.
The ME and CFS Capita Selecta Quarterly is funded by donations. The editors would like to thank Dr. Anne Macintyre, Ms. Goeman and the M.E. Association of Norway for their financial support during 1998.
We are now accepting donations to help us continue our work during 1999. Those wishing to support this publication should send a cheque or IMO (in sterling) to the 'ME and CFS Medical Update'.
Copyright EM. Goudsmit 1998.
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