An approach to chronic fatigue syndrome in adults

Abstract:

BACKGROUND: The neurologist is often asked to evaluate patients with a chief complaint of fatigue. Many neurologists do not believe in the pathologically based disease known as chronic fatigue syndrome, yet as a group, neurologists are well suited to guide the diagnostic work up of such patients to pinpoint treatable disorders in the realm of neurology, general medicine, and psychiatry.

REVIEW SUMMARY: Every patient should be carefully evaluated for certain medical, psychiatric, and neurologic disease that can cause fatigue as the most prominent symptom. This is most pressing because new work in virology, immunology, and imaging holds promise but still does not provide any diagnostic test or a mechanism for the production of these symptoms. Only a few treatments meet with even modest success in CFS. The goal of this paper is to provide the clinical neurologist with a framework for the investigation and management of this challenging group of patients.

CONCLUSIONS: Neurologists are typically also trained in psychiatry and general medicine, and this is a strong position to evaluate the patient with fatigue. Because no presently available test can make the diagnosis of CFS, the assessment is vital to seek out more treatable illnesses.

 

Source: Sabin TD. An approach to chronic fatigue syndrome in adults. Neurologist. 2003 Jan;9(1):28-34. http://www.ncbi.nlm.nih.gov/pubmed/12801429

 

Deficit in motor performance correlates with changed corticospinal excitability in patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is characterised by fatigue and musculosketetal pain, the severity of which is variable. Simple reaction times (SRTs) and movement times (SMTs) are slowed in CFS. Our objective is to correlate the day-to-day changes in symptomatology with any change in SRT, SMT or corticospinal excitability.

Ten CFS patients were tested on two occasions up to two years apart. Motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) of the motor cortex were recorded from the thenar muscles. Threshold TMS strength to evoke MEPs was measured to index corticospinal excitability. SRTs and SMTs were measured.

The percentage change in both SRTs and SMTs between the two test sessions correlated with the percentage change in corticospinal excitability assessed according to threshold TMS intensity required to produce MEPs. This study provides evidence that changing motor deficits in CFS have a neurophysiological basis. The slowness of SRTs supports the notion of a deficit in motor preparatory areas of the brain.

 

Source: Davey NJ, Puri BK, Catley M, Main J, Nowicky AV, Zaman R. Deficit in motor performance correlates with changed corticospinal excitability in patients with chronic fatigue syndrome. Int J Clin Pract. 2003 May;57(4):262-4. http://www.ncbi.nlm.nih.gov/pubmed/12800454

 

Assessing chronic fatigue

Comment on: The head-up tilt test with haemodynamic instability score in diagnosing chronic fatigue syndrome. [QJM. 2003]

 

Naschitz et al.1 studied patients with chronic fatigue syndrome (CFS) in comparison with some controls ‘exhibiting shared clinical features with CFS’, namely, patients with non-CFS chronic fatigue, fibromyalgia, generalized anxiety disorder, and neurally mediated syncope. Considering that those controls were included in the study on the basis of the clinical overlap of their disorders with CFS, it is surprising that Naschitz et al. failed to include also patients with Addison’s disease, which resembles CFS far more closely than does any other medical condition.2

You can read the rest of this comment here: http://qjmed.oxfordjournals.org/content/96/6/454.long

 

Source: Baschetti R. Assessing chronic fatigue. QJM. 2003 Jun;96(6):454. http://qjmed.oxfordjournals.org/content/96/6/454.long (Full article)

 

Chronic phase lipids in sera of chronic fatigue syndrome (CFS), chronic ciguatera fish poisoning (CCFP), hepatitis B, and cancer with antigenic epitope resembling ciguatoxin, as assessed with MAb-CTX

Abstract:

Clinical reports and descriptions of chronic fatigue syndrome (CFS) and chronic ciguatera fish poisoning (CCFP) show great similarities in clinical symptomology. These similarities in the literature suggested the exploration of lipids in sera of CFS, CCFP, and other diseases with the membrane immunobead assay (MIA), which is typically used for screening ciguateric ocean fish. Sera from patients with other diseases, including hepatitis B, cancer, and diabetes, were included to assess the degree of specificity involved.

Sera were treated with acetone in a ratio of 1 part serum to 4 parts acetone. The suspension was centrifuged, and the acetone layer was evaporated. The residue was weighed and redissolved in 1.0 mL methanol and tested by the MIA, undiluted and titered to 1:160. The undiluted acetone fraction of the 37 normal showed +/- activity to +activity with 16 no titer, 15 with 1:5 titer and two with 1:10 titer, and four with > or =1:40 titers. One hundred fifteen CFS sera showed 1 with 1+ and 114 with 2+ activity in the undiluted samples, 1 with 1:10 titer, 3 with 1:20 titer, 31 with 1:40 titer, 50 with 1:80 titer, and 30 with 160 titer. Thus 95.6% of the samples had > or =1:40 titer.

Eight hepatitis B sera samples had > or =1:40 titers. Four CCFP samples had > or =1:40 titers. Three of 16 cancer samples had 1:40 titer. These data are summarized in Fig. 1. As shown in Table 1, a significant increase (P<0.001) in the chronic phase lipids (CPLs) was shown relative to the normal group. A preliminary chemical study in C18 octadecylsilyl columns showed all fractions (100% chloroform, 9:1 chloroform : methanol, 1:1 chloroform : methanol, and 100% methanol) to contain lipids reactive to MAb-CTX with different intensities. Prostaglandins were shown in 100% methanol fraction.

Competitive MIA with crude fish ciguatoxin and CFS with synthetic JKLM ciguatoxin epitope suggested similarities in structure with ciguatoxin. This was compatible with the neuroblastoma assay demonstrated in the C(18) column fractions 9:1 and 1:1, chloroform : methanol solvents.

Copyright 2003 John Wiley & Sons, Ltd.

 

Source: Hokama Y, Uto GA, Palafox NA, Enlander D, Jordan E, Cocchetto A. Chronic phase lipids in sera of chronic fatigue syndrome (CFS), chronic ciguatera fish poisoning (CCFP), hepatitis B, and cancer with antigenic epitope resembling ciguatoxin, as assessed with MAb-CTX. J Clin Lab Anal. 2003;17(4):132-9. http://www.ncbi.nlm.nih.gov/pubmed/12784262

 

Subclassifying chronic fatigue syndrome through exercise testing

Abstract:

PURPOSE: The purpose of this study was to examine physiological responses of persons with chronic fatigue syndrome (CFS) to a graded exercise test.

METHODS: Cardiopulmonary exercise tests were performed on 189 patients diagnosed with CFS. Based on values for peak oxygen consumption, patients were assigned to one of four impairment categories (none, mild, moderate, and severe), using American Medical Association (AMA) guidelines. A one-way MANOVA was used to determine differences between impairment categories for the dependent variables of age, body mass index, percentage of predicted [OV0312]O(2), resting and peak heart rates, resting and peak systolic blood pressure, respiratory quotient (RQ), and rating of perceived exertion.

RESULTS: Significant differences were found between each impairment level for percentage of predicted [OV0312]O(2) and peak heart rate. Peak systolic blood pressure values for the “moderate,” and “severe” groups differed significantly from each other and both other groups. The more impaired groups had lower values. The no impairment group had a significantly higher peak RQ than each of the other impairment levels (all P < 0.001). Peak [OV0312]O(2) values were less than predicted for all groups. Compared with the males, the women achieved actual values for peak [OV0312]O(2) that were closer to their predicted values.

CONCLUSION: Despite a common diagnosis, the functional capacity of CFS patients varies greatly. Stratifying patients by function allows for a more meaningful interpretation of the responses to exercise and may enable differential diagnosis between subsets of CFS patients.

Comment in: Physiological factors limiting exercise performance in CFS. [Med Sci Sports Exerc. 2004]

 

Source: Vanness JM, Snell CR, Strayer DR, Dempsey L 4th, Stevens SR. Subclassifying chronic fatigue syndrome through exercise testing. Med Sci Sports Exerc. 2003 Jun;35(6):908-13. http://www.ncbi.nlm.nih.gov/pubmed/12783037

 

Fatigue, burnout, and chronic fatigue syndrome among employees on sick leave: do attributions make the difference?

Abstract:

BACKGROUND: Persistent fatigue among employees, burnout, and chronic fatigue syndrome (CFS) are three fatigue conditions that share some characteristics in theory. However, these conditions have not been compared in empirical research, despite conceptual similarities.

METHODS: This cross sectional study aimed to investigate relations between persistent fatigue, burnout, and CFS by describing the clinical features of a sample of 151 fatigued employees on sick leave. Using validated instruments, subgroups based on research criteria for CFS and burnout within the sample of fatigued employees and a reference group of 97 diagnosed CFS patients were compared. Analyses of covariance were performed.

RESULTS: A total of 66 (43.7%) fatigued employees met research criteria for CFS (except symptom criteria) and 76 (50.3%) met research criteria for burnout. “CFS-like employees” (fatigued employees who met CFS criteria) reported stronger somatic attributions than “non-CFS-like employees”. Burnt out CFS-like employees were more depressed and distressed than CFS-like employees who were not burnt out. Burnout cases among the non-CFS-like employees had stronger psychological attributions than fatigued employees who were not burnt out. Compared to diagnosed CFS patients, CFS-like employees merely had a shorter duration of fatigue complaints. Burnt out CFS-like employees had stronger psychological attributions and were more distressed than CFS patients.

CONCLUSIONS: Fatigued employees shared many important characteristics with CFS patients, regardless of burnout status, and many fatigued employees met CFS criteria and/or burnout criteria. Differences however concerned the causal attributions that were made. This raises questions about the role of causal attributions: are they modified by fatigue complaints or do they determine illness outcome?

 

Source: Huibers MJ, Beurskens AJ, Prins JB, Kant IJ, Bazelmans E, Van Schayck CP, Knottnerus JA, Bleijenberg G. Fatigue, burnout, and chronic fatigue syndrome among employees on sick leave: do attributions make the difference? Occup Environ Med. 2003 Jun;60 Suppl 1:i26-31. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1765721/ (Full article)

 

Atypical depression as a secondary symptom in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) has gained prominence since 1988 and a substantial amount of research has been done in this domain. However, it is still regarded as a controversial condition. Moreover, most of the symptoms of CFS itself are non-specific, occurring in many illnesses; some of the symptoms are also common in depression. Indeed, an area of continued controversy and debate involves the diagnostic overlap between CFS and psychiatric disorders. Through anecdotal evidence, atypical depression appears to be common in CFS. Recent developments in psychobiology underscore the role of the acute phase response and its associated sickness behavior in affective disorders. Thus, we hypothesize that atypical depression is sickness behavior rather than an affective disorder as shown by anecdotal evidence in CFS.

 

Source: Van Hoof E, Cluydts R, De Meirleir K. Atypical depression as a secondary symptom in chronic fatigue syndrome. Med Hypotheses. 2003 Jul;61(1):52-5. http://www.ncbi.nlm.nih.gov/pubmed/12781640

 

Chronic fatigue and organophosphate pesticides in sheep farming: a retrospective study amongst people reporting to a UK pharmacovigilance scheme

Abstract:

The Department of Health has recently published a report from the CFS/ME Working Group which concluded that chronic fatigue syndrome (CFS) should be recognized as a chronic illness. Symptoms consistent with CFS are often reported by people who consider their health has been affected by exposure to pesticides, but the Working Group concluded that this type of exposure is not a common trigger for the syndrome.

The Veterinary Medicines Directorate (VMD) collects self-assessed reports of ill health in humans associated with veterinary medicines under their Suspected Adverse Reaction Surveillance Scheme. The reporters have mainly been sheep farmers. These reports were used to investigate the possible relationship between chronic fatigue (CF) and exposure to organophosphate pesticides in sheep farming. The overall aim of the study was to investigate a possible association between exposure to organophosphates and the development of CF amongst people who consider their health has been affected by pesticides in sheep farming. The hypothesis investigated was that repeated exposure to organophosphate pesticides in sheep dip may increase the probability of developing CF. A group of mostly sheep farmers who had reported to the VMD surveillance scheme were identified.

We planned to use a retrospective case-control study design but the initial symptoms reports were not sufficiently reliable to enable this. The study population was asked to complete two questionnaires. The first questionnaire was designed to identify the history of exposure of subjects to organophosphate pesticides, and their exposure was then reconstructed using a metric specifically developed for this purpose. The second questionnaire collected detailed information to identify whether the subjects had CF when they originally reported to the VMD and at the time of the survey.

The questionnaire was sent to a total of 206 subjects, of whom 28 had moved home. A total of 37% of the remaining 178 subjects participated. There was a high prevalence of CF amongst those who completed the questionnaire and this has generally persisted since the subjects reported to the VMD. Higher CF scores were associated with higher exposure to organophosphate pesticides.

CF is very common amongst those who consider their health was affected by pesticides and we have shown there is limited evidence of an association between exposure to organophosphates and CF. Further research is needed to investigate the cause of this syndrome amongst farmers exposed to pesticides.

 

Source: Tahmaz N, Soutar A, Cherrie JW. Chronic fatigue and organophosphate pesticides in sheep farming: a retrospective study amongst people reporting to a UK pharmacovigilance scheme. Ann Occup Hyg. 2003 Jun;47(4):261-7. http://annhyg.oxfordjournals.org/content/47/4/261.long (Full article)

 

Examining the influence of biological and psychological factors on cognitive performance in chronic fatigue syndrome: a randomized, double-blind, placebo-controlled, crossover study

Abstract:

The pathophysiology of chronic fatigue syndrome (CFS) remains unclear; however, both biological and psychological factors have been implicated in establishing or maintaining this condition. People with CFS report significant and disabling cognitive difficulties such as impaired concentration that in some cases are exacerbated by exposure to chemical triggers. The aim of this study was to determine if neuropsychological deficits in CFS are triggered by exposure to chemicals, or perceptions about the properties of these substances.

Participants were 36 people with a primary diagnosis of CFS, defined according to Centers for Disease Control (CDC) criteria. A randomized, double-blind, placebo-controlled, crossover design was used, with objective assessment of neuropsychological function and participant rating of substance type, before and after exposure to placebo or chemical trigger. Results showed decrements in neuropsychological tests scores on three out of four outcome measures when participants rated the substance they had been exposed to as “chemical.” No change in performance was found based on actual substance type.

These results suggest that cognitive attributions about exposure substances in people with CFS may be associated with worse performance on neuropsychological tasks. In addition, these findings suggest that psychological interventions aimed at modifying substance-related cognitions may reduce some symptoms of CFS.

 

Source: Smith S, Sullivan K. Examining the influence of biological and psychological factors on cognitive performance in chronic fatigue syndrome: a randomized, double-blind, placebo-controlled, crossover study. Int J Behav Med. 2003;10(2):162-73. http://www.ncbi.nlm.nih.gov/pubmed/12763708

 

Comparison of subjective and objective measures of insomnia in monozygotic twins discordant for chronic fatigue syndrome

Abstract:

STUDY OBJECTIVES: To examine the objective and subjective measures of insomnia in chronic fatigue syndrome (CFS).

DESIGN: Monozygotic co-twin control study.

SETTING: Academic medical center.

PATIENTS OR PARTICIPANTS: Twenty-two pairs of monozygotic twins where 1 member of the pair had CFS and the other did not.

INTERVENTIONS: N/A.

MEASUREMENTS AND RESULTS: Twenty-two CFS-discordant twin pairs completed a Sleep Disorders Questionnaire, overnight polysomnography, and a postpolysomnography sleep survey. Mean and percent differences in the sleep measures were compared between the CFS and healthy twins using matched-pair methods of analysis. Compared with their healthy co-twins, the CFS twins more frequently endorsed 8 subjective measures of insomnia and poor sleep (all p < or = 0.05). However, the CFS and healthy twins did not differ in objective polysomnographic measures of insomnia, including sleep latency, total sleep time, sleep efficiency, arousal number, arousal index, hypnogram awakenings, rapid eye movement (REM)-sleep latency, and percent stages 1, 2, and 3-4 (delta). Percent stage REM sleep was increased in the CFS twins compared with the healthy twins (27.7% vs. 24.4%, p < or = 0.05). On the postpolysomnography survey, CFS twins reported that they had slept fewer hours (6.2 vs. 6.7; p < or = 0.05), and were less well rested (p < or = 0.001) compared to their co-twins.

CONCLUSIONS: CFS patients had worse subjective sleep than their co-twins despite little objective data supporting this discrepancy, suggesting they suffer from an element of sleep-state misperception. The higher percentage of REM sleep in the CFS twins implies that REM sleep may play a role in this illness.

 

Source: Watson NF, Kapur V, Arguelles LM, Goldberg J, Schmidt DF, Armitage R, Buchwald D. Comparison of subjective and objective measures of insomnia in monozygotic twins discordant for chronic fatigue syndrome. Sleep. 2003 May 1;26(3):324-8. http://www.ncbi.nlm.nih.gov/pubmed/12749553