Cognitive behaviour therapy for the chronic fatigue syndrome: a randomized controlled trial.

OBJECTIVE--To evaluate the acceptability and efficacy of adding cognitive behaviour therapy to the medical care of patients presenting with the chronic fatigue syndrome. DESIGN--Randomised controlled trial with final assessment at 12 months. SETTING--An infectious diseases outpatient clinic. SUBJECTS--60 consecutively referred patients meeting consensus criteria for the chronic fatigue syndrome. INTERVENTIONS--Medical care comprised assessment, advice, and follow up in general practice. Patients who received cognitive behaviour therapy were offered 16 individual weekly sessions in addition to their medical care. MAIN OUTCOME MEASURES--The proportions of patients (a) who achieved normal daily functioning (Karnofsky score 80 or more) and (b) who achieved a clinically significant improvement in functioning (change in Karnofsky score 10 points or more) by 12 months after randomisation. RESULTS--Only two eligible patients refused to participate. All randomised patients completed treatment. An intention to treat analysis showed that 73% (22/30) of recipients of cognitive behaviour therapy achieved a satisfactory outcome as compared with 27% (8/30) of patients who were given only medical care (difference 47 percentage points; 95% confidence interval 24 to 69). Similar differences were observed in subsidiary outcome measures. The improvement in disability among patients given cognitive behaviour therapy continued after completion of therapy. Illness beliefs and coping behaviour previously associated with a poor outcome changed more with cognitive behaviour therapy than with medical care alone. CONCLUSION--Adding cognitive behaviour therapy to the medical care of patients with the chronic fatigue syndrome is acceptable to patients and leads to a sustained reduction in functional impairment.     

Apathy/depression, but not subjective fatigue, is related with cognitive dysfunction in patients with multiple sclerosis

Background

Cognitive impairment could affect quality of life for patients with multiple sclerosis (MS), and cognitive function may be correlated with several factors such as depression and fatigue. This study aimed to evaluate cognitive function in Japanese patients with MS and the association between cognitive function and apathy, fatigue, and depression.

Methods

The Brief Repeatable Battery of Neuropsychological tests (BRB-N) was performed in 184 Japanese patients with MS and 163 healthy controls matched for age, gender, and education. The Apathy Scale (AS), Fatigue Questionnaire (FQ), and Beck Depression Inventory Second Edition (BDI-II) were used to evaluate apathy, fatigue, and depression, respectively. Student’s t-test was used to compare MS patients and healthy controls. Correlations between two factors were assessed using the Pearson correlation test, and multiple regression analysis was used to evaluate how much each factor affected the BRB-N score.

Results

In all BRB-N tests, patients with MS scored significantly lower than controls, and the effect size of symbol digit modalities test was the highest among the 9 tests of the BRB-N. Patients with MS had higher AS (p?<?0.001), FQ (p?<?0.0001), and BDI-II (p?<?0.0001) scores than controls. In patients with MS, scores on most of the BRB-N tests correlated with scores on the AS and BDI-II; however, there was little correlation between scores on the BRB-N tests and those on the FQ.

Conclusions

Cognitive function was impaired, particularly information-processing speed, and decreased cognitive function was correlated with apathy and depression in Japanese patients with MS. Despite the association between cognitive variables and depression/apathy, cognitive function was impaired beyond the effect of depression and apathy. However, subjective fatigue is not related with cognitive impairment. Taken together, this suggests that different therapeutic approaches are needed to improve subjective fatigue and cognition, and thereby quality of life, in patients with MS.     

A multiple course trial of desferrioxamine in chronic progressive multiple sclerosis.

Chronic progressive multiple sclerosis (MS) is a debilitating disease that is often refractory to treatment. We have previously published a pilot study using a single 2-week course of the iron chelating drug, desferrioxamine (DFO), as a candidate drug for treatment of this form of MS. In this study, we gave 9 patients up to 8 courses of this regimen over 2 years. The patients tolerated the medication well. During the study, 1 patient improved, 3 remained stable, and 5 worsened by 0.5 on the Kurtzke expanded disability status scale (EDSS). These results suggest that, while the drug is well tolerated, no effect on disease progression can be identified at this dosage level. A more continuous dosage schedule could be studied as a candidate for treatment in this disease process.     

Low frequency fatigue in human quadriceps is fatigue dependent and not task dependent.

It is well accepted that a low intensity/long duration isometric contraction induces more low frequency fatigue (LFF) compared to a high-intensity/short-duration contraction. However, previous reports examined the intensity/duration of the contraction but did not control the level of fatigue when concluding fatigue is task dependent. The purpose of this study was to determine whether a long duration/low intensity fatiguing contraction would induce greater LFF than a short duration/high-intensity contraction when the quadriceps muscle was fatigued to similar levels. Eighteen healthy male subjects performed quadriceps contractions sustained at 35% and 65% of maximal voluntary contraction (MVC) on separate days, until the tasks induced a similar amount of fatigue (force generating capacity=45% MVC). Double pulse torque to single pulse torque ratio (D/S ratio) was obtained before, immediately and 5min after fatigue along with the electromyographic (EMG) signal from vastus medialis (VM) and rectus femoris (RF). The D/S ratio significantly (p<0.05) increased by 8.7+/-8.5% (mean+/-SD) and 10.2+/-9.2% after 35% and 65% tasks, respectively, and remained elevated 5min into recovery; however, there was no significant difference in ratio between the two sessions immediately or 5min post-fatigue (p>0.05) even though the endurance time for the 35% fatigue task (124+/-39.68s) was significantly longer (p=0.05) than that of the 65% task (63+/-17.73s). EMG amplitude and median power frequency (MPF) analysis also did not reveal any significant differences between these two sessions after fatigue. These findings indicate that LFF fatigue is fatigue dependent as well as task intensity/duration dependent. These findings assist us in understanding task dependency and muscle fatigue.     

Professional and popular views of chronic fatigue syndrome.

OBJECTIVE--To study the coverage of the chronic fatigue syndrome in the popular and professional press. DESIGN--Search of all original research papers on the chronic fatigue syndrome published in British journals from 1980 onwards and of professional trade papers, national newspapers, and women''s magazines. Interviews with six medical journalists. SETTING--British scientific, medical, and popular press. RESULTS--37 (49%) articles in research journals did not favour organic causes and 23 (31%) favoured organic causes. By contrast 31 (55%) articles in the medical trade press and 118 (69%) in national newspapers and women''s magazines favoured organic causes. CONCLUSIONS--Press coverage of chronic fatigue syndrome has amplified and distorted divisions in the research community concerning the chronic fatigue syndrome. Articles in the press concentrate on a simple medical model of illness reinforcing the stigma of psychological illness and dissatisfaction with traditional medical authority.     

Cytokine responses to acute and chronic exercise in multiple sclerosis.

Regular exercise reduces functional loss associated with multiple sclerosis (MS). However, the impact of exercise on inflammatory mediators associated with disease activity remains relatively unexplored. The purpose of this study was to determine whether ambulatory MS subjects would respond similarly to aerobic cycle training compared with matched controls on circulating immune variables, interleukin (IL)-6, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma. Eleven MS and 11 non-MS control subjects (8 women and 3 men in both groups) matched in age, height, body mass, body fat, and peak O(2) uptake completed the study. Subjects completed 30 min of cycle ergometry at 60% of peak O(2) uptake, 3 day/wk for 8 wk. Plasma cytokine concentrations were determined before and after exercise at weeks 0, 4, and 8. MS and control subjects showed a similar cytokine responses to exercise. IL-6 at rest tended to decrease (P = 0.08) with training in both groups. Resting plasma TNF-alpha tended to be higher in MS compared with controls throughout the study (P = 0.08). MS subjects showed elevated resting TNF-alpha in MS at the end of the 8-wk program (P = 0.04), whereas resting TNF-alpha remained unchanged in controls (P > 0.05). Resting plasma IFN-gamma at rest was elevated in MS subjects (P = 0.008) and unchanged in controls at the end of the intervention (P > 0.05). The response of plasma IL-6, TNF-alpha, and IFN-gamma after a single bout of exercise was similar between MS and control subjects (P > 0.05). Additional research to understand the impact of exercise on immune variables in MS is warranted.     

Abnormalities of sleep in patients with the chronic fatigue syndrome.

OBJECTIVE--To determine whether patients with the chronic fatigue syndrome have abnormalities of sleep which may contribute to daytime fatigue. DESIGN--A case-control study of the sleep of patients with the chronic fatigue syndrome and that of healthy volunteers. SETTING--An infectious disease outpatient clinic and subjects'' homes. SUBJECTS--12 patients who met research criteria for the chronic fatigue syndrome but not for major depressive disorder and 12 healthy controls matched for age, sex, and weight. MAIN OUTCOME MEASURES--Subjective reports of sleep from patients'' diaries and measurement of sleep patterns by polysomnography. Subjects'' anxiety, depression, and functional impairment were assessed by interview. RESULTS--Patients with the chronic fatigue syndrome spent more time in bed than controls (544 min v 465 min, p < 0.001) but slept less efficiently (90% v 96%, p < 0.05) and spent more time awake after initially going to sleep (31.9 min v 16.6 min, p < 0.05). Seven patients with the chronic fatigue syndrome had a sleep disorder (four had difficulty maintaining sleep, one had difficulty getting to sleep, one had difficulty in both initiating and maintaining sleep, and one had hypersomnia) compared with none of the controls (p = 0.003). Those with sleep disorders showed greater functional impairment than the remaining five patients (score on general health survey 50.4% v 70.4%, p < 0.05), but their psychiatric scores were not significantly different. CONCLUSIONS--Most patients with the chronic fatigue syndrome had sleep disorders, which are likely to contribute to daytime fatigue. Sleep disorders may be important in the aetiology of the syndrome.     

Increased daily physical activity and fatigue symptoms in chronic fatigue syndrome

Individuals with chronic fatigue syndrome (CFS) have been shown to have reduced activity levels associated with heightened feelings of fatigue. Previous research has demonstrated that exercise training has beneficial effects on fatigue-related symptoms in individuals with CFS. PURPOSE: The aim of this study was to sustain an increase in daily physical activity in CFS patients for 4 weeks and assess the effects on fatigue, muscle pain and overall mood. METHODS: Six CFS and seven sedentary controls were studied. Daily activity was assessed by a CSA accelerometer. Following a two week baseline period, CFS subjects were asked to increase their daily physical activity by 30% over baseline by walking a prescribed amount each day for a period of four weeks. Fatigue, muscle pain and overall mood were reported daily using a 0 to 100 visual analog scale and weekly using the Profile of Mood States (Bipolar) questionnaire. RESULTS: CFS patients had significantly lower daily activity counts than controls (162.5 +/- 51.7 x 103 counts/day vs. 267.2 +/- 79.5 x 103 counts/day) during a 2-week baseline period. At baseline, the CFS patients reported significantly (P < 0.01) higher fatigue and muscle pain intensity compared to controls but the groups did not differ in overall mood. CFS subjects increased their daily activity by 28 +/- 19.7% over a 4 week period. Overall mood and muscle pain worsened in the CFS patients with increased activity. CONCLUSION: CFS patients were able to increase their daily physical activity for a period of four weeks. In contrast to previous studies fatigue, muscle pain, and overall mood did not improve with increased activity. Increased activity was not presented as a treatment which may account for the differential findings between this and previous studies. The results suggest that a daily "activity limit" may exist in this population. Future studies on the impact of physical activity on the symptoms of CFS patients are needed.     

A community-based study of seasonal variation in the onset of chronic fatigue syndrome and idiopathic chronic fatigue

One proposed hypothesis regarding the etiology of chronic fatigue syndrome (CFS) is that there is a subgroup of patients in which symptom onset is precipitated by a viral infection. If this is indeed true, then one would anticipate a greater incidence of the emergence of CFS symptoms during months when viral infections occur with the greatest frequency. The current community-based epidemiology study examined the month of symptom onset for 31 patients with CFS and 44 others with idiopathic chronic fatigue (ICF). It was determined that the distribution of the month of illness onset for the CFS and ICF groups was nonrandom, with greater numbers of participants than expected reporting an onset of CFS and ICF during January. (Chronobiology International, 18(2), 315-319, 2001)     

A functional polymorphism in the disrupted-in schizophrenia 1 gene is associated with chronic fatigue syndrome

AimsDisrupted-in schizophrenia 1 (DISC1), identified in a pedigree with a familial psychosis with the chromosome translocation (1:11), is a putative susceptibility gene for psychoses such as schizophrenia and major depressive disorder (MDD). Patients with chronic fatigue syndrome (CFS) report having continuous severe fatigue and many overlapping symptoms with MDD; however, the mechanism and effective treatment of CFS are still unclear. We focused on the overlapping symptoms between CFS and MDD and performed an association study of the functional single-nucleotide polymorphism (SNP) in the DISC1 gene with CFS.Main methodsVenous blood was drawn from CFS patients and controls and genomic DNA was extracted from the whole blood according to standard procedures. Ser704Cys DISC1 SNP was genotyped using the TaqMan 5′-exonuclease allelic discrimination assay.Key findingsWe found that the Cys704 allele of Ser704Cys SNP was associated with an increased risk of CFS development compared with the Ser704 allele.SignificanceDISC1 Ser704Cys might be a functional variant that affects one of the mechanisms implicated in the biology of CFS. Some patients with CFS showed a phenotype similar to that of patients with MDD, but further studies are needed to clarify the biological mechanism, because this study is of a rather preliminary nature. Despite the variety of patients with CFS, DISC1 Ser704Cys has an association with CFS, which may also suggest that DISC1 plays a central role in the induction of various psychiatric diseases.