Number 2 |
1st June 2007 |
NEUROLOGY
|
Cook, DB., O'Connor, PJ., Lange, G and Steffener, J. Functional neuroimaging correlates of mental fatigue induced by cognition among chronic fatigue syndrome patients and controls. Neuroimage, 2007 Mar 3; [Epub ahead of print]. doi:10.1016/j.neuroimage.2007.02.033
The neural mechanisms underlying feelings of fatigue are poorly understood. The primary purpose of the study was to use functional magnetic resonance imaging (fMRI) to determine the association between feelings of mental fatigue and blood oxygen level dependent (BOLD) brain responses during a mentally fatiguing cognitive task.
Healthy, non-fatigued controls and patients with CFS (CDC criteria ’94) were included to determine the influence of chronic levels of fatigue on brain responses. We hypothesized that mental fatigue would be significantly related to brain activity during a fatiguing cognitive task but not during either a non-fatiguing motor (finger tapping) or cognitive (auditory monitoring) task. Patients (n=9) and controls (n=11) completed a finger tapping task, a simple auditory monitoring task and a challenging working memory task, designed to induce mental fatigue, while undergoing fMRI. Fatigue was measured prior to scanning and following each task during fMRI data collection.
Results showed that mental fatigue was significantly related to brain activity during the fatiguing cognitive task but not the finger tapping or simple auditory monitoring tasks. Significant (p<0.005) positive relationships were found for cerebellar, temporal, cingulate and frontal regions. A significant (p=0.001) negative relationship was found for the left posterior parietal cortex. CFS participants did not differ from controls for either finger tapping or auditory monitoring tasks, but exhibited significantly greater activity in several cortical and subcortical regions during the fatiguing cognitive task.
Our results suggest an association between subjective feelings of mental fatigue and brain responses during fatiguing cognition.
Natelson, BH., Intriligator, R., Cherniack, NS., Chandler, HK and Stewart, JM. Hypocapnia is a biological marker for orthostatic intolerance in some patients with chronic fatigue syndrome. Dynamic Medicine, 2007, 6:2. doi:10.1186/1476-5918-6-2
Patients with CFS and those with orthostatic intolerance share many symptoms, yet questions exist as to whether CFS patients have physiological evidence of orthostatic intolerance. The aim is to determine if some CFS patients have increased rates of orthostatic hypotension, hypertension, tachycardia, or hypocapnia relative to age-matched controls. Assessed were blood pressure, heart rate, respiratory rate, end tidal CO2 and visual analogue scales for orthostatic symptoms when supine and when standing for 8 minutes without moving legs.
Subjects were 60 women and 15 men with CFS (CDC criteria ’94) and 36 women and 4 men serving as age matched controls with analyses confined to 62 patients and 35 controls showing either normal orthostatic testing or a physiological abnormal test. Main outcome measures were orthostatic tachycardia; orthostatic hypotension; orthostatic hypertension; orthostatic hypocapnia or combinations thereof.
CFS patients had higher rates of abnormal tests than controls (53% vs 20%, p<.002), but rates of orthostatic tachycardia, orthostatic hypotension, and orthostatic hypertension did not differ significantly between patients and controls (11.3% vs 5.7%, 6.5% vs 2.9%, 19.4% vs 11.4%, respectively). In contrast, rates of orthostatic hypocapnia were significantly higher in CFS than in controls (20.6% vs 2.9%, p<.02). This CFS group reported significantly more feelings of illness and shortness of breath than either controls or CFS patients with normal physiological tests.
Conclusion: A substantial number of CFS patients have orthostatic intolerance in the form of orthostatic hypocapnia. This allows subgrouping of patients with CFS and thus reduces patient pool heterogeneity engendered by use of a clinical case definition.
http://www.dynamic-med.com/content/pdf/1476-5918-6-2.pdf
Nijs, J., Demol, S and Wallman, K. Can submaximal exercise variables predict peak exercise performance in women with chronic fatigue syndrome? Archives of Medical Research, 2007, 38, 3, 350-353. doi:10.1016/j.arcmed.2006.10.009
This study aimed at examining whether physiological exercise variables at the submaximal level, defined as 75% of the age-predicted target heart rate, are able to predict peak exercise performance in women with CFS (CDC criteria ’94, n=222).
Subjects performed a bicycle ergometric test against a graded increase in workload until exhaustion with continuous monitoring of electrocardiographic and ventilatory variables. Oxygen uptake at the submaximal level (VO2SUBMAX) correlated strongly with peak oxygen uptake (VO2PEAK) (r=0.70). For the prediction of VO2PEAK, linear regression analysis determined the line of best fit as: VO2PEAK= 0:95 x VO2SUBMAX + 372.3.
Using this equation, the mean error in the prediction was 14.6 + 11.2% (range 0.1-63.7%). It is concluded that the prediction of VO2PEAK based on VO2SUBMAX might be useful for analyzing group differences or treatment effects but not for individual (clinical) purposes.
Takken, T., Henneken, T., van de Putte, E., Helders, P and Engelbert, R. Exercise testing in children and adolescents with chronic fatigue syndrome. International Journal of Sports Medicine, 2007 Mar 15; [Epub ahead of print]. doi: 10.1055/s-2007-964888
The objective of this study was to evaluate exercise capacity in children and adolescents diagnosed with CFS. We examined 20 patients (12 girls and 8 boys; mean age 14.9 +/- 3.7 years) diagnosed with CFS. Exercise capacity was measured using a maximal exercise test on a bicycle ergometer and an expired gas analysis system. Fatigue was assessed using a questionnaire and a daily activity diary was used to describe activities for three days. Z-scores were calculated using age- and sex-matched reference values.
Z-scores in children and adolescents with CFS were - 0.33 +/- 1.0 (p=0.17) for peak oxygen uptake, - 1.13 +/- 1.41 (p=0.002) for relative peak oxygen uptake [ml/kg/min] and - 0.93 +/- 1.29 (p=0.07) for maximal work load. Both heart rate and blood pressure at peak performance were significantly reduced compared to reference values. Fatigue levels were significantly positively associated with age and negatively with blood pressure at peak exercise (p<0.05).
In conclusion maximum exercise testing was feasible in young people with CFS. Maximal exercise capacity was only reduced in a minority of the patients and was related to current physical activity levels.
Van Hoof, E., De Becker, P., Lapp, C., Cluydts, R and De Meirleir, K. Defining the occurrence and influence of alpha-delta sleep in chronic fatigue syndrome. American Journal of Medical Science, 2007, 333, 2, 78-84.
Patients with CFS present a disordered sleep pattern and frequently undergo polysomnography to exclude a primary sleep disorder. Such studies have shown reduced sleep efficiency, a reduction of deep sleep, prolonged sleep initiation, and alpha-wave intrusion during deep sleep. Deregulation of the 2-5A synthetase/RNase L antiviral pathway and a potential acquired channelopathy are also found in a subset of CFS patients and could lead to sleep disturbances. This article compiles a large sleep study database on CFS patients and correlates these data with a limited number of immune parameters as it has been thought that RNase L could be associated with these sleep disturbances.
Forty-eight patients who fulfilled CDC criteria ‘94 underwent extensive medical evaluation, routine laboratory testing, and a structured psychiatric interview. Subjects then completed a complaint checklist (scores 0-3) and a two-night polysomnographic investigation. RNase L analysis was performed by gel electrophoresis using a radiolabeled 2',5'-oligoadenylate trimer. Basic descriptive statistical parameters were calculated.
Seventy per cent reported significant fatigue and 75% noted post-exertional fatigue. Patients experienced a prolonged sleep latency, showed a low sleep efficiency index, and had a low percentage of slow wave sleep. The present alpha-delta intrusion correlated with anxiety; no correlations appeared, however, between alpha-delta sleep and immunologic parameters, including RNase L.
Thus the main findings are validation of sleep latency problems and other sleep disturbances as already suggested by several authors; alpha-delta intrusion seems associated with anxiety; and elevated RNase L did not correlate with alpha-delta sleep.
Wallman, KE and Sacco, P. Sense of effort during a fatiguing exercise protocol in chronic fatigue syndrome. Research in Sports Medicine, 2007, 15, 1, 47-59.
The purpose of this study was to determine whether CFS subjects would produce greater force production in their matching limb during a fatiguing contralateral limb-matching task of the elbow flexors, compared with healthy, matched controls.
Eight CFS subjects and 8 healthy, matched control subjects participated in a fatiguing task that consisted of intermittent submaximal contractions (30% maximal voluntary contraction) of the nondominant arm performed over a 45 min duration. Each minute, the subject attempted to match the force of the nondominant arm with their dominant arm (without visual feedback for the dominant arm).
Results showed that average matching force and ratings of perceived effort values were significantly higher in the CFS group during the fatiguing task (p=0.04, p=0.02, respectively). This study demonstrated objectively that CFS subjects experienced a greater sense of effort in the elbow flexors while performing a fatiguing task.
Edwards, CR., Thompson, AR and Blair A. An 'Overwhelming Illness': women's experiences of learning to live with chronic fatigue syndrome/myalgic encephalomyelitis. Journal of Health Psychology, 2007, 12, 2, 203-214.
The processes through which people learn to live with CFS/ME are poorly understood and have not been rigorously explored within the literature. Semi-structured interviews were conducted with eight women recruited from a self-help network and analysed using interpretative phenomenological analysis.
Participants initially described being 'overwhelmed' by CFS/ME. Attempts at seeking help were unsatisfactory and participants described feeling let down and disbelieved. Participants reacted to this by identifying types of 'self-help' and assertively taking more responsibility for their illness and its treatment. Acquiring social support and greater knowledge were key mediating factors in the emergence of control and acceptance. The relevance of the themes to existing research and the implications for clinical practice are considered.
[Ed. Note: This article reveals the lack of sound information about pacing in the public domain and challenges the view that there is no requirement for guidance. “All participants spoke about a gradually developing recognition of the need to learn to live within their bodies’ limitations. Some described this as ‘pacing’, others described this as ‘ride with it’ (Claire) and ‘rest a bit, do a bit’ (Elizabeth). By learning about their limits and living within them participants described feeling more in control. This was a dramatic change from the experiences described in phase one where participants typically felt overwhelmed and out of control: ‘Your body needs rest, but you need a regime and you need to be working towards something and pacing yourself, and nobody tells you how to pace yourself’ (Hanna). Pacing was learnt gradually through ‘trial and error’ (Alice) and by ‘learning what your body’s saying to you’ (Debra). Participants felt there was a lack of information about how to do this, they had to work it out for themselves. Despite an understanding of the importance of pacing, participants described finding it extremely hard to stay within their limits. Four of the participants described at times ignoring their limitations or ‘kicking against it’ (Debra). This was generally described as being a choice they made if an activity was worth the resulting ‘payback’ (Debra). Some participants also found that the demands of their daily life meant they were forced to exceed their limits, it was felt to be impossible to live within the limits their illness placed on them.” (p. 208)]
Rimes, KA., Goodman, R., Hotopf, M., Wessely, S., Meltzer, H and Chalder, T. Incidence, prognosis, and risk factors for fatigue and chronic fatigue syndrome in adolescents: a prospective community study. Pediatrics, 2007, 119, 3 E603-E609. doi:10.1542/peds.2006-2231
The objective of this study was to describe the incidence, prevalence, risk factors, and prognosis of fatigue, chronic fatigue, and CFS in 11 to 15-year-olds.
A random general population sample (n=842) of British adolescents and their parents were assessed at baseline (Time 1) and 4 to 6 months later (Time 2). The main outcomes were fatigue, chronic fatigue, and CFS (CDC criteria ‘94, operationalised, no medical examination or tests to rule out other diagnoses). Measures for mothers included the GHQ-12.
The incidence over 4 to 6 months was 30.3% for fatigue, 1.1% for chronic fatigue, and 0.5% for CFS. The point prevalence was 34.1% and 38.1% for fatigue, 0.4% and 1.1% for chronic fatigue, and 0.1% and 0.5% for CFS at Time 1 and Time 2, respectively. Of participants who were fatigued at Time 1, 53% remained fatigued at Time 2. The 3 cases of chronic fatigue and 1 case of CFS at Time 1 had recovered by Time 2. Higher risk for development of chronic fatigue at Time 2 was associated with Time 1 anxiety or depression, conduct disorder, and maternal distress; in multivariate analysis, baseline anxiety or depression remained a significant predictor of chronic fatigue. Increased risk for development of fatigue at Time 2 was associated with Time 1 anxiety or depression, conduct disorder, and older age; in multivariate analyses, these factors and female gender all were significant predictors of fatigue. Of the four cases of CFS at Time 2, only 1 had post-exertional fatigue.
The incidence rates for chronic fatigue and CFS in this adolescent sample were relatively high, but the prognosis for these conditions was good. This prospective study provides evidence for an association between emotional/behavioral problems and subsequent onset of fatigue/chronic fatigue.
Henningsen, P., Zipfel, S and Herzog, W. Management of functional somatic syndromes. Lancet, 2007, 369, 946-955.
[Ed. Note: A selective review which fails to consider many of the differences between the syndromes and which exaggerates the role of psychiatric factors in disorders such as CFS, e.g. on personality disorders, generalising from other reviews on FSS rather than basing arguments on research. It illustrates the continued editorial policy to psychologise disorders such as CFS].
Tanriverdi, F., Karaca, Z., Unluhizarci, K and Kelestimur F. The hypothalamo-pituitary-adrenal axis in chronic fatigue syndrome and fibromyalgia syndrome. Stress, 2007, 10, 1, 13-25.
The hypothalamo-pituitary-adrenal (HPA) axis plays a major role in the regulation of responses to stress. Human stress-related disorders such as CFS, fibromyalgia syndrome (FMS), chronic pelvic pain and post-traumatic stress disorder are characterized by alterations in HPA axis activity. However, the role of the HPA axis alterations in these stress-related disorders is not clear. Most studies have shown that the HPA axis is underactive in the stress-related disorders, but contradictory results have also been reported, which may be due to the patients selected for the study, the methods used for the investigation of the HPA axis, the stage of the syndrome when the tests have been done and the interpretation of the results.
There is no structural abnormality in the endocrine organs which comprise the HPA axis, thus it seems that hypocortisolemia found in the patients with stress-related disorder is functional. It may be also an adaptive response of the body to chronic stress. In this review, tests used in the assessment of HPA axis function and the HPA axis alterations found in CFS and FMS are discussed in detail.
Van Geelen, SM., Sinnema, G., Hermans, HJ and Kuis, W. Personality and chronic fatigue syndrome: methodological and conceptual issues. Clinical Psychology Review, 2007 Jan 27; [Epub ahead of print]. doi:10.1016/j.cpr.2007.01.010
Among clinical psychologists, consulting physicians, scientific researchers and society in general an image has emerged of patients with CFS as perfectionist, conscientious, hardworking, somewhat neurotic and introverted individuals with high personal standards, a great desire to be socially accepted and with a history of continuously pushing themselves past their limits. The aim of this article is to (a) give a concise review of the main recent studies on personality and CFS, (b) address the major methodological problems in the study of personality in CFS and (c) discuss some of the conceptual assumptions that seem to limit the research on personality and CFS.
The results of the reviewed studies range from no evidence of major differences between the personalities of patients with CFS and controls, to evidence of severe psychopathology and personality disorder in patients with CFS. Although personality seems to play a role in CFS, it is difficult to draw general conclusions on the relation between personality and CFS. It is argued that this is partially due to the diversity and heterogeneity in study methods, patient populations, control groups and CFS case definitions. Personality should be regarded as an important factor to be studied in CFS. However, additional studies are needed, not focusing exclusively on personality disorder, or personality considered on a general trait level. In recent developments in personality research, the continually evolving life narrative that makes sense of, and gives direction to, an individual's life is also regarded as an important aspect of personality. New insights into personality and CFS might be gained by systematically studying the self-narratives of patients with the syndrome.
Wyller, VB. The chronic fatigue syndrome. An update. Acta Neurologica Scandinavica, Suppl. 2007, 187, 7-14.
Appel, S., Chapman, J and Shoenfeld, Y. Infection and vaccination in chronic fatigue syndrome: myth or reality? Autoimmunity, 2007, 40, 1, 48-53.
The current concept is that CFS pathogenesis is a multi factorial condition in which an infective agent cause an aberrant immune response characterized by a shift to Th-2 dominant response. When the response fails to be switched-off, a chronic immune activation occurs and is clinically expressed as the symptomatology of CFS. Vaccinations are used in order to stimulate the immune system to induce a persistent immunity against the favorable antigens. Several syndromes that contain chronic fatigue as one of their symptoms, such as “Gulf war syndrome” and macrophagic myofasciitis were related to vaccinations. Can vaccinations induce the aberrant immune response of CFS? Little is known about this issue. There are some reports on CFS occurring after vaccination, but few prospective and retrospective studies… A working group of the Canadian Laboratory Center for Disease Control (LCDC) that was founded in order to examine the suspected association between CFS and vaccinations concluded that there is no evidence that relates CFS to vaccination. Further studies are requested to examine this issue since it is very conceivable that if infection can lead to CFS, vaccination may also lead to it in the same immune-mediated pathogenesis.
[Ed. Note: This article includes misleading information about psychological aspects and some factual errors. For example: “...CFS patients tend to present psychiatric problems such as depression and low self estimation and the Oxford criteria for the diagnosis of CFS requires the presence of mental disturbances in order to determine this diagnosis.” The Oxford criteria requires mental fatigue, which is not necessarily linked to psychiatric disturbances.]
Boiko, AN., Batysheva, TT., Matvievskaya, OV., Manevich, TM and Gusev, EI. Characteristics of the formation of chronic fatigue syndrome and approaches to its treatment in young patients with focal brain damage. Neuroscience and Behavioral Physiology, 2007, 37, 221-228.
Chronic fatigue is among the manifestations of focal brain lesions. It is most often encountered in multiple sclerosis (MS) and patients with the sequelae of traumatic, inflammatory, and vascular brain damage (encephalopathies). The aim of the present work was to study the mechanisms of formation of this syndrome in 50 patients with focal brain lesions of different origins (in the inactive stage) and to assess the possibility of correcting it using the combined agent Fezam (2 capsules t.i.d. for one month), which contains piracetam and cinarrizine. In patients with encephalopathies, CFS was directly associated with the severity of depression. Patients with MS showed changes in the value-sense sphere. Neuropsychological testing showed that the psychological and personality components played a greater role in the origins of chronic fatigue in patients with encephalopathies than in those with MS. Fezam significantly decreased the severity of chronic fatigue, particularly in patients with MS; in the second group (non-MS patients) this was accompanied by a decrease in the severity of depression. Mild side effects (in six patients — 12%) consisted generally of sleep disturbances. These results indicate that Fezam should be used in the treatment of chronic fatigue in patients with focal brain lesions; in encephalopathies it should be combined with psychoactive agents.
http://springerlink.metapress.com/content/j6h0q4p32j61/?p=c2e1f31a5c9e488f96f5e715ad872343&pi=0
Frémont, M., Vaeyens, F., Vincent Herst, C., De Meirleir, K and Englebienne, P. Antiviral pathway deregulation of chronic fatigue syndrome induces nitric oxide production in immune cells that precludes a resolution of the inflammatory response. Journal of Chronic Fatigue Syndrome, 2006, 13, 4, 17-28.
CFS is a poorly defined medical condition diagnosed by exclusion, which, besides severe chronic fatigue as the hallmark symptom, involves inflammatory and immune activation stigma. Although viral infections are not systematically found in CFS patients, the type I interferon antiviral pathway has been repeatedly shown to be activated in peripheral blood mononuclear cells (PBMC) of the most afflicted patients. An abnormal truncated form of ribonuclease L (37-kDa RNase L) is also found in the PBMC of CFS patients and this protein has been proposed as a biological marker for CFS. Recently, the levels of this abnormal protein have been significantly correlated to the extent of inflammatory symptoms displayed by CFS patients. We report here that active double-stranded RNA-dependent kinase (PKR) is expressed and activated in parallel to the presence of the 37-kDa RNase L and to an increase in nitric oxide production by immune cells. However, PKR upregulation results also in a significant increase followed by a decrease in caspase 3 activity for the samples containing the highest levels of 37-kDa RNase L. This caspase 3 downregulation does not result from increased expression of the anti-apoptotic proteins Bcl-2 and Bcl-XL.
These results therefore suggest that chronic inflammation due to excess nitric oxide production plays a role in CFS and that the normal resolution of the inflammatory process by NF-KB activation and apoptotic induction is impaired. These observations draw new directions for the therapeutic approach of CFS.
Gottfries, C-G., Häger, O., Regland, B and Zachrisson, O. Long-term treatment with a staphylococcus toxoid vaccine in patients with fibromyalgia and chronic fatigue syndrome. Journal of Chronic Fatigue Syndrome, 2006, 13, 4, 29-40.
One hundred and sixty patients with fibromyalgia as well as CFS, who were on a continuous treatment with a Staphylococcus vaccine, were followed during one year with repeated consultation visits. The patients had participated in controlled studies and been on continuous treatment with the vaccine for 22+10 months before inclusion into this follow-up study. They were treated with 1 mL of the vaccine subcutaneously every third to fourth week. Adverse events were few. The adherence to the treatment was very good. Over a period of one year, 8% withdrew, and in only 5%, the withdrawal was due to insufficient clinical effect. Only in two cases where the patients were allergic to the preservative of the vaccine, the side effects caused the withdrawal of the treatment. Ratings with scales (CPRS-15 and FibroFatigue) showed improvement from start of treatment and also further improvement during the follow-up year. In view of the natural history for these disorders, the result is of interest.
Gray, SE and Rutter, DR. Illness representations in young people with chronic fatigue syndrome. Psychology and Health, 2007, 22, 2, 159-174.
Study on 85 young people with CFS recruited from a self-help group, to test hypotheses based on Leventhal’s model of self-regulation. One finding showed a relationship between accommodating to the illness, which includes pacing, and quality of life. Focusing on symptoms had a negative association with the latter. Maintaining activity, consistent with GET, mediated between believing the illness was caused by risk factors (not viruses or psychological problems) and better perceived physical functioning.
Hawk, C., Jason, LA and Torres-Harding, S. Reliability of a chronic fatigue syndrome questionnaire. Journal of Chronic Fatigue Syndrome, 2006, 13, 4, 41-66.
A diagnostic instrument, the CFS Questionnaire, was developed for clinicians and researchers to administer to their patients as a screening instrument for CFS. The CFS Questionnaire is comprehensive, covering the inclusionary and exclusionary self-report criteria of the current U.S. case definition (Fukuda et al. 1994). The instrument also assesses past and current activity levels, and symptoms of post-exertional malaise to ensure these items are adequately assessed.
The goal of the present study was to evaluate the diagnostic reliability of an experimental measure for assessing CFS. This instrument was administered to 15 persons with CFS, 15 persons with major depressive disorder (MDD), and 15 controls. Using the Fukuda et al. (1994) diagnostic criteria, raters independently reviewed participants' CFS Questionnaire responses and rated whether each study participant met criteria for CFS.
This instrument demonstrated good inter-rater reliability. Further, this instrument demonstrated adequate classification accuracy, with a 9.3 positive likelihood ratio and a .08 negative likelihood ratio. Overall, the CFS Questionnaire demonstrated good test-retest reliability, with intra-class correlation coefficients and kappa coefficients at .70 or higher for most items. Lower test-retest reliability coefficients were found for some items assessing temporal symptoms or items requiring an estimate of time.
The present study suggests that the CFS Questionnaire is a reliable diagnostic tool. Use of the CFS Questionnaire should promote higher levels of diagnostic reliability because it allows for accurate classification of individuals with CFS.
Jones, JF., Maloney, EM., Boneva, RS., Jones, AB and Reeves, WC. Complementary and alternative medical therapy utilization by people with chronic fatiguing illnesses in the United States. BMC Complementary and Alternative Medicine, 2007 Apr 25, 7(1):12 [Epub ahead of print]. doi:10.1186/1472-6882-7-12
Four hundred and forty fatigued and 444 non-fatigued persons from 2,728 households completed screening. Fatigued subjects included 53 persons with prolonged fatigue, 338 with chronic fatigue, and 49 with CFS-like illness (CDC criteria ’94, no medical examination). Mind-body therapy (primarily personal prayer and prayer by others) was the most frequently used CAM across all groups. Among women, there was a significant trend of increasing overall CAM use across all subgroups (p-trend=0.003). All categories of CAM use were associated with significantly poorer physical health scores, and all but one (alternative medicine systems) were associated with significantly poorer mental health scores. People with CFS-like illness were significantly more likely to use body-based therapy (chiropractic and massage) than non-fatigued participants (OR=2.52, CI=1.32, 4.82). Use of body-based therapies increased significantly in a linear trend across subgroups of non-fatigued, prolonged fatigued, chronic fatigued, and CFS-like subjects (p-trend = 0.002). People with chronic fatigue were also significantly more likely to use body-based therapy (OR=1.52, CI=1.07, 2.16) and mind-body (excluding prayer) therapy than non-fatigued participants (OR=1.73, CI=1.20 - 2.48).
http://www.biomedcentral.com/1472-6882/7/12
Kasatkin, DS and Spirin, NN. Possible mechanisms of the formation of chronic fatigue syndrome in the clinical picture of multiple sclerosis. Neuroscience and Behavioral Physiology, 2007, 37, 215-219.
[Ed. Note: Speculative article.]
Kaufman, KR and Goodnick, PJ. Depression, chronic fatigue syndrome, and fibromyalgia: An Update. Journal of Chronic Fatigue Syndrome, 2006, 13, 4, 77-106.
Centers for Disease Control criteria for CFS specifically recognize that patients can have both CFS and depression. The clinician's challenge is to judge for each individual patient whether the complaint of fatigue is primarily depression, physical illness, such as CFS, or a combination of both. This review differentiates CFS and fibromyalgia, discussed as "chronic fatigue syndrome and related immune deficiency syndromes" (CFIDS), from depression in terms of physical signs, symptoms, biological parameters, brain imaging, immunology, and treatment. The review focuses on practical applications of research findings with a further focus on future ability to show clear biologic separation and specific treatment.
When depressive symptoms exist with those of CFS, accurate differentiation can usually be accomplished by focusing on diagnostic criteria. Presence of multiple physical signs and symptoms of CFIDS may be of great value. In terms of laboratory testing, a single helpful test may be measuring the plasma cortisol, which is usually high in depression and low in CFS. Future research should focus on the combination of plasma cortisol with an index of serotonin function, which is high in CFIDS and low in depression. Additional research should focus on neuroimaging and immune differentiation. Combination of multiple tests should result in a significant and clinically useful separation between CFIDS and MDD.
In treating patients with significant depression or MDD with CFIDS, one should think of the noradrenergic approach using bupropion or low-dose tricyclic antidepressants in combination with a selective serotonin reuptake inhibitor, especially sertraline, to aid improvement of global, pain, and immunologic parameters. Alternatively, serotonin norepinephrine reuptake inhibitors (venlafaxine and duloxetine) should be considered. Future treatment research should focus on larger placebo-controlled, double-blind trials of these and other antidepressants as well as the evaluation of psychostimulants, electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS).
Ed. Note: In the literature on CFS, the D in CFIDS usually refers to dysfunction.]
Knoop, H., Prins, JB., Stulemeijer, M., van der Meer, JWM and Bleijenberg, G. The effect of cognitive behaviour therapy for chronic fatigue syndrome on self-reported cognitive impairments and neuropsychological test performance. Journal of Neurology, Neurosurgery, and Psychiatry, 2007, 78, 434-436.
Patients with CFS often have concentration and memory problems. Neuropsychological test performance is impaired in at least a subgroup of patients with CFS. Cognitive behavioural therapy (CBT) for CFS leads to a reduction in fatigue and disabilities. The aim of the study was to test the hypothesis that CBT results in a reduction of self-reported cognitive impairment and in an improved neuropsychological test performance.
Data of two previous randomised controlled trials were used. One study compared CBT for adult patients with CFS (CDC criteria ‘94, n=78), with two control conditions (n=76 and 79 resp. All: median duration of illness= 41months). The second study compared CBT for adolescent patients (n=33) with a waiting list condition (n=34, all: median duration of illness: 18 months). Self-reported cognitive impairment was assessed with questionnaires. Information speed was measured with simple and choice reaction time tasks. Adults also completed the symbol digit-modalities task, a measure of complex attentional function.
In both studies, the level of self-reported cognitive impairment decreased significantly more after CBT than in the control conditions (e.g Cohen’s d for five items from CIS = 1.3 in adults, d=.6 in adolescents, based on change within treatment condition). Neuropsychological test performance did not improve.
CBT leads to a reduction in self-reported cognitive impairment, but not to improved neuro-psychological test performance. The findings of this study support the idea that the distorted perception of cognitive processes is more central to CFS than actual cognitive performance.
[Ed. Note: There are alleged concerns about undeclared exclusion criteria in studies from this team and the findings should therefore be interpreted with caution.]
Knoop, H., Bleijenberg, G., Gielissen, MFM., van der Meer, JWM and White, PD. Is a full recovery possible after cognitive behavioural therapy for chronic fatigue syndrome? Psychotherapy and Psychosomatics, 2007, 76, 171-176.
CBT for CFS leads to a decrease in symptoms and disabilities. There is controversy about the nature of the change following treatment; some suggest that patients improve by learning to adapt to a chronic condition, others think that recovery is possible. The objective of this study was to find out whether recovery from CFS is possible after CBT.
The researchers assessed the outcome of a cohort of 96 patients treated with CBT between September 2003 and May 2005. All were diagnosed with CFS (1994 CDC plus additional criteria); the mean duration of the illness was 70.8 months (range 12–276 months, SD 52.8). Twenty-two of the 96 patients (23%) had a medical co-morbid condition beside CFS (e.g. controlled diabetes, asthma etc). Eleven per cent dropped out of the original group. The definition of recovery was based on the absence of the CDC criteria for CFS, but also took into account the perception of the patients' fatigue and their own health. Data from healthy population norms were used in calculating conservative thresholds for recovery.
After treatment, 69% of the patients no longer met the CDC criteria for CFS. The percentage of recovered patients depended on the criteria used for recovery. Using the most comprehensive definition of recovery, 23% of the patients fully recovered. Fewer patients with a co-morbid medical condition recovered. Significant improvement following CBT is probable and a full recovery is possible. Sharing this information with patients can raise the expectations of the treatment, which may enhance outcomes without raising false hopes.
Knoop, H., Stulemeijer, M., Prins, JB., van der Meer, JWM and Bleijenberg, G. Is cognitive behaviour therapy for chronic fatigue syndrome also effective for pain symptoms? Behaviour Research and Therapy, 2007, Mar 14, in press. doi:10.1016/j.brat.2007.03.002
Patients with CFS frequently report chronic pain symptoms. CBT for CFS results in a reduction of fatigue, but is not aimed at pain symptoms. In this study, we tested the hypothesis that a successful treatment of CFS can also lead to a reduction of pain. The second objective was to explore possible mechanisms of changes in pain. The third objective was to assess the predictive value of pain for treatment outcome. Data from two previous CBT studies were used, one of adult CFS patients (n=96) and one of adolescent CFS patients (n=32). Pain severity was assessed with a daily self-observation list at baseline and post-treatment. The location of pain in adults was assessed with the McGill Pain Questionnaire (MPQ). Patients were divided into recovered and non-recovered groups. Recovery was defined as reaching a post-treatment level of fatigue within normal range.
Recovered adult and adolescent CFS patients reported a significant reduction of pain severity compared to non-recovered patients. Recovered adult patients also had fewer pain locations following treatment. The decrease in fatigue predicted the change in pain severity. In adult patients, a higher pain severity at baseline was associated with a negative treatment outcome.
Njoku, MGC., Jason, LA and Torres-Harding, SR. The prevalence of chronic fatigue syndrome in Nigeria. Journal of Health Psychology, 2007, 12, 3, 461-474.
The present study found adult rates of CFS in Nigeria that were somewhat higher than rates from community-based CFS epidemiologic studies in the USA. The rates of chronic fatigue for both adults and children were also higher than in existing community-based studies. It is possible that the presence of several fatiguing illnesses such as malaria and typhoid, the lack of adequate healthcare resources and poverty in Nigeria, place individuals at greater risk for fatigue and its syndromes. There is a need for more epidemiologic studies on the prevalence and socio-demographic characteristics of CFS in developing countries.
Rowe, PC and Lucas, KE. Orthostatic intolerance in chronic fatigue syndrome. American Journal of Medicine, 207, 120, 3, Page e13.
Letter noting that in a previous study by Jones et al (ibid 2005, 118, 1415e19-1415e28), the sample was too small to allow firm conclusions to be drawn about the prevalence of orthostatic intolerance overall in those with CFS, or about the relative prevalence of postural tachycardia or neurally mediated hypotension in this group. They also correct an error: “the combined prevalence of orthostatic intolerance was 66%, not 62% as reported in Table 7... Table 7 also includes some minor typographical errors: reference 20 appears twice (it should be reference 21 the first time, then reference 8 the second time), and reference 34 in Table 7 should be reference 37.
“In our studies of orthostatic intolerance, now totalling over 220 subjects with CFS, quiet upright posture has been a strong and consistent physiologic stressor in over 95%. Even when not accompanied by hemodynamic changes, orthostatic stress typically has been associated with a provocation or exacerbation of characteristic CFS symptoms. Others have shown that these symptoms and hemodynamic abnormalities with orthostatic stress can be reversed upon application of external lower-body compression (reference 37). Whether orthostatic disorders are primary or secondary, this evidence suggests that they play an important contributing role in the phenomenology of the illness for a substantial proportion of affected individuals.”
Taylor, RR., Kulkarni, S and Shiraishi, Y. Conservation of resources and quality of life in individuals with chronic fatigue syndrome. Journal of Chronic Fatigue Syndrome, 2006, 13, 4, 3-15.
The objective was to examine the relationship between resources and quality of life in individuals with CFS. A cross-sectional design was used to describe associations between resource loss and gain and quality of life for 47 individuals with CFS [many recruited from self-help groups and advertisements, Ed.] The Conservation of Resources Evaluation was used to measure resources in terms of perceived loss and gain. Health-related quality of life was assessed with the Quality of Life Index.
Total resource loss and total resource gain were significant correlates of overall quality of life. Gains in self-esteem, energy, and work resources were associated with higher-perceived quality of life. Material loss and energy loss were associated with lower-perceived quality of life. Findings for the relationships between perceived resources of self-esteem, work, material items, and energy and perceived quality of life can be used to improve rehabilitation efforts. These relationships appear to occur independently of illness severity among individuals CFS.
Ter Wolbeek, M., van Doornen, LJ., Coffeng, LE., Kavelaars, A and Heijnen CJ. Cortisol and severe fatigue: A longitudinal study in adolescent girls. Psychoneuroendocrinology, 2007, 32, 2, 171-182.
Fatigue is a common complaint among adolescents, especially in girls, and is associated with high rates of school absenteeism. Severe fatigue is often accompanied by psychological and physical symptoms. In CFS, functioning of the HPA-axis has previously been found to be altered. The aim of the present study was to investigate whether cortisol production is deviant in fatigued adolescent girls from the general population and to study longitudinal changes in fatigue in association with possible changes in HPA-axis functioning.
In the cross-sectional part of the study the cortisol response to awakening (CAR) and to a low-dose oral dexamethasone were examined in a group of fatigued adolescent girls (n=87) in comparison to a non-fatigued control group (n=77). Questionnaires regarding fatigue, depression, anxiety, sleep quality, somatic symptoms and CFS-related symptoms were filled out. Follow up measurements were performed after 6 and 12 months.
While the fatigued and non-fatigued group differed remarkably on all symptom self-reports, no differences between groups in CAR and response to dexamethasone were observed. Girls in the fatigued group remained fatigued over time and reported high levels of other psychological and physical symptoms during the whole year of the study. The CAR varied between time points but correlated non-systematically with situational characteristics or symptom reports.
We conclude that trait-like fatigue, as measured in a sample of adolescent girls from a high school population, is not reflected in a dysregulation as assessed on the level of salivary cortisol after awakening.
Ullrich, PM., Afari, N., Jacobsen, C., Goldberg, J and Buchwald, D. Cold pressor pain sensitivity in monozygotic twins discordant for chronic fatigue syndrome. Pain Medicine, 2007, 8, 3, 216-222.
Individuals with CFS experience many pain symptoms. The present study examined whether pain and fatigue ratings and pain threshold and tolerance levels for cold pain differed between twins with CFS and their co-twins without CFS.
The study used a co-twin control design to assess cold pain sensitivity, pain, and fatigue in monozygotic twins discordant for CFS. The sample comprised 15 monozygotic twin pairs discordant for CFS recruited from the volunteer Chronic Fatigue Twin Registry at the University of Washington.
Although cold pain threshold and tolerance levels were slightly lower in twins with CFS than their co-twins without CFS, these differences failed to reach statistical significance. Subjective ratings of pain and fatigue at multiple time points during the experimental protocol among twins with CFS were significantly higher than ratings of pain (p=0.003) and fatigue (p<0.001) by their co-twins without CFS.
These results, while preliminary, highlight the perceptual and cognitive components to the pain experience in CFS. Future studies should focus on examining the heritability of pain sensitivity and the underlying mechanisms involved in the perception of pain sensitivity in CFS.
White, PD., Sharpe, MC., Chalder, T., DeCesare, JC., Walwyn, R and the PACE trial group. Protocol for the PACE trial: A randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome / myalgic encephalomyelitis or encephalopathy. BMC Neurology, 2007, 7:6. doi:10.1186/1471-2377-7-6
http://www.biomedcentral.com/content/pdf/1471-2377-7-6.pdf
Shor, S. Lyme Disease presenting as chronic fatigue syndrome. Journal of Chronic Fatigue Syndrome, 2006, 13, 4, 67-75.
CFS by definition represents a diagnosis of exclusion. Late stage or "Chronic Lyme" infection with or without "co-infections" is a difficult diagnosis to establish. The symptom complex of both conditions can be very similar. This case study represents an attempt to support serious consideration for a subpopulation of patients otherwise diagnosed with "CFS," as actually representing chronic Lyme disease.
[Ed. Note: The current CDC definition of CFS with its emphasis on fatigue may complicate diagnosis. Ramsay’s description of ME focused on the delayed recovery of muscle power after minimal exertion. This aspect of ‘fatigue’ might help to differentiate ME from similar disorders.]
Wyller, VB., Due, R., Saul, JP., Amlie, JP and Thaulow, R. Usefulness of an abnormal cardiovascular response during low-grade head-up tilt-test for discriminating adolescents with chronic fatigue from healthy controls. American Journal of Cardiology, 2007, 99, 997-1001.
Hemodynamic dysfunction is documented in CFS. This study was conducted to investigate cardiovascular responses to orthostatic stress in adolescents with CFS (fatigue for 4 months, no accompanying symptoms required), using a novel procedure for tilt-table testing. A total of 27 adolescents with CFS and 33 healthy control subjects with equal age and gender distribution underwent 15 minutes of 20° head-up tilt testing. Heart rate, systolic blood pressure (BP), mean BP, diastolic BP, stroke index, total peripheral resistance index, end-diastolic volume index, and acceleration index were continuously and non-invasively recorded.
At rest, patients with CFS had higher total peripheral resistance index values (p<0.01) and lower stroke index and end-diastolic volume index values (p<0.05) than controls. During 20° head-up tilt testing, patients with CFS had greater increases in heart rate, diastolic BP (p<0.001), mean BP (p<0.01), and total peripheral resistance index (p<0.05) than controls and greater decreases in stroke index (p<0.05). Syncope or near syncope was not observed.
In conclusion, this study found that adolescents with CFS have significant abnormalities of cardiovascular regulation in response to mild orthostatic stress, differentiating them from healthy controls.
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