Chronic Fatigue Syndrome: Bleijenberg G

Bleijenberg G. · No affiliation provided · Health Qual Life Outcomes. · Pubmed #14613570 links to  free full text

This publication has no abstract.

Zwarts MJ, Bleijenberg G, van Engelen BG. · University Medical Centre Nijmegen, Institute of Neurology, 920 Department of Clinical Neurophysiology, PO Box 9101, 6500 HB Nijmegen, The Netherlands. · Clin Neurophysiol. · Pubmed #18039594 No free full text.

Abstract: Fatigue is a multidimensional concept covering both physiological and psychological aspects. Chronic fatigue is a typical symptom of diseases such as cancer, multiple sclerosis (MS), Parkinson's disease (PD) and cerebrovascular disorders but is also presented by people in whom no defined somatic disease has been established. If certain criteria are met, chronic fatigue syndrome can be diagnosed. The 4-item Abbreviated Fatigue Questionnaire allows the extent of the experienced fatigue to be assessed with a high degree of reliability and validity. Physiological fatigue has been well defined and originates in both the peripheral and central nervous system. The condition can be assessed by combining force and surface-EMG measurements (including frequency analyses and muscle-fibre conduction estimations), twitch interpolation, magnetic stimulation of the motor cortex and analysis of changes in the readiness potential. Fatigue is a well-known phenomenon in both central and peripheral neurological disorders. Examples of the former conditions are multiple sclerosis, Parkinson's disease and stroke. Although it seems to be a universal symptom of many brain disorders, the unique characteristics of the concomitant fatigue also point to a specific relationship with several of these syndromes. As regards neuromuscular disorders, fatigue has been reported in patients with post-polio syndrome, myasthenia gravis, Guillain-Barré syndrome, facioscapulohumeral dystrophy, myotonic dystrophy and hereditary motor and sensory neuropathy type-I. More than 60% of all neuromuscular patients suffer from severe fatigue, a prevalence resembling that of patients with MS. Except for several rare myopathies with specific metabolic derangements leading to exercise-induced muscle fatigue, most studies have not identified a prominent peripheral cause for the fatigue in this population. In contrast, the central activation of the diseased neuromuscular system is generally found to be suboptimal. The reliability of the psychological and clinical neurophysiological assessment techniques available today allows a multidisciplinary approach to fatigue in neurological patients, which may contribute to the elucidation of the pathophysiological mechanisms of chronic fatigue, with the ultimate goal to develop tailored treatments for fatigue in neurological patients. The present report discusses the different manifestations of fatigue and the available tools to assess peripheral and central fatigue.

Prins JB, van der Meer JW, Bleijenberg G. · Department of Medical Psychology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands. · Lancet. · Pubmed #16443043 No free full text.

Abstract: During the past two decades, there has been heated debate about chronic fatigue syndrome (CFS) among researchers, practitioners, and patients. Few illnesses have been discussed so extensively. The existence of the disorder has been questioned, its underlying pathophysiology debated, and an effective treatment opposed; patients' organisations have participated in scientific discussions. In this review, we look back on several controversies over CFS with respect to its definition, diagnosis, pathophysiology, and treatment. We review issues of epidemiology and clinical manifestations, focusing on the scientific status of CFS. Modern neuroscience and genetics research offer interesting findings for new hypotheses on the aetiology and pathogenesis of the illness. We also discuss promising future issues, such as psychopathophysiology and mechanisms of improvement, and suggest multidisciplinary prospective studies of CFS and fatigue in the general population. These studies should pay particular attention to similarities to and differences from functional somatic syndromes and other fatiguing conditions.

Van Engelen BG, Kalkman JS, Schillings ML, Van Der Werf SP, Bleijenberg G, Zwarts MJ. · Neuromusculair Centrum Nijmegen, Instituut voor Neurologie, Universitair Medisch Centrum St Radboud, Postbus 9101, 6500 HB Nijmegen. · Ned Tijdschr Geneeskd. · Pubmed #15283024 No free full text.

Abstract: Chronic fatigue is a symptom of diseases such as cancer, multiple sclerosis, Parkinson's and cerebrovascular disease. Fatigue can also be present in people with no demonstrable somatic disease. If certain criteria are met, chronic-fatigue syndrome may be diagnosed in these cases. Fatigue is a multi-dimensional concept with physiological and psychological dimensions. The 'Short Fatigue Questionnaire' consisting of 4 questions is a tool to measure fatigue with a high degree of reliability and validity. Within the group of neuromuscular disorders, fatigue has been reported by patients with post-polio syndrome, myasthenia gravis, and Guillain-Barré syndrome. The percentage of neuromuscular patients suffering from severe fatigue (64%) is comparable with that of patients with multiple sclerosis, a disease in which fatigue is an acknowledged symptom. Now that reliable psychological and clinical neurophysiological techniques are available, a multidisciplinary approach to fatigue in patients with well-defined neuromuscular disorders may contribute towards the elucidation of the pathophysiological mechanisms of chronic fatigue, with the ultimate goal being to develop methods of treatment for fatigue in neuromuscular patients.

Reeves WC, Lloyd A, Vernon SD, Klimas N, Jason LA, Bleijenberg G, Evengard B, White PD, Nisenbaum R, Unger ER, Anonymous00371. · Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America. · BMC Health Serv Res. · Pubmed #14702202 links to  free full text

Abstract: BACKGROUND: Chronic fatigue syndrome (CFS) is defined by symptoms and disability, has no confirmatory physical signs or characteristic laboratory abnormalities, and the etiology and pathophysiology remain unknown. Difficulties with accurate case ascertainment contribute to this ignorance. METHODS: Experienced investigators from around the world who are involved in CFS research met for a series of three day workshops in 2000, 2001 and 2002 intended to identify the problems in application of the current CFS case definition. The investigators were divided into focus groups and each group was charged with a topic. The investigators in each focus group relied on their own clinical and scientific knowledge, brainstorming within each group and with all investigators when focus group summaries were presented. Relevant literature was selected and reviewed independent of the workshops. The relevant literature was circulated via list-serves and resolved as being relevant by group consensus. Focus group reports were analyzed and compiled into the recommendations presented here. RESULTS: Ambiguities in the current CFS research definition that contribute to inconsistent case identification were identified. Recommendations for use of the definition, standardization of classification instruments and study design issues are presented that are intended to improve the precision of case ascertainment. The International CFS Study Group also identified ambiguities associated with exclusionary and comorbid conditions and reviewed the standardized, internationally applicable instruments used to measure symptoms, fatigue intensity and associated disability. CONCLUSION: This paper provides an approach to guide systematic, and hopefully reproducible, application of the current case definition, so that case ascertainment would be more uniform across sites. Ultimately, an operational CFS case definition will need to be based on empirical studies designed to delineate the possibly distinct biological pathways that result in chronic fatigue.

van Heukelom RO, Prins JB, Smits MG, Bleijenberg G. · Department of Neurology, Sleep-Wake Disorders and Chronobiology, Hospital De Gelderse Vallei, Ede, and Department of Medical Psychology, Radbound University Medical Centre, Nijmegen, The Netherlands. · Eur J Neurol. · Pubmed #16420393 No free full text.

Abstract: The effect of melatonin, a chronobiotic drug, was explored in 29 patients with chronic fatigue syndrome (CFS) and Dim Light Melatonin onset (DLMO) later than 21.30 hours, reflective of delayed circadian rhythmicity. The patients took 5 mg of melatonin orally, 5 h before DLMO during 3 months. Their responses to the checklist individual strength (CIS), a reliable questionnaire measuring the severity of personally experienced fatigue, were assessed twice with a 6-week interval immediately before the treatment and once after 3 months treatment. In the pre-treatment period the fatigue sub-score improved significantly. After treatment, the total CIS score and the sub-scores for fatigue, concentration, motivation and activity improved significantly. The sub-score fatigue normalized in two of the 29 patients in the pre-treatment period and in eight of 27 patients during treatment. This change was significant. In the patients with DLMO later than 22.00 hours (n=21) the total CIS score and the sub-scores for fatigue, concentration and activity improved significantly more than in the patients (n=8) with DLMO earlier than 22.00 hours. Melatonin may be an effective treatment for patients with CFS and late DLMO, especially in those with DLMO later than 22.00 hours.

Bazelmans E, Prins JB, Lulofs R, van der Meer JW, Bleijenberg G, Anonymous00352. · Department of Medical Psychology, University Medical Centre Nijmegen, Nijmegen, The Netherlands. · Psychother Psychosom. · Pubmed #15947511 No free full text.

Abstract: BACKGROUND: It has been demonstrated that individual cognitive behaviour therapy is an effective treatment for chronic fatigue syndrome (CFS). The aim of the present study was to investigate the effectiveness of cognitive behaviour group therapy (CBGT) in an unselected group of CFS patients. Additionally, pretreatment characteristics of CFS patients who improve after CBGT were explored. METHODS: In a non-randomised waiting list controlled design, 31 patients were allocated to CBGT and 36 to the waiting list condition. CBGT consisted of 12 two-hour sessions during 6 months. Main outcome measures were fatigue (Checklist Individual Strength) and functional impairment (Sickness Impact Profile). RESULTS: A moderate effect on fatigue in favour of CBGT was found. For functional impairment, the effect was opposite to what was expected. Patients who improved after CBGT had less complaints at baseline compared to patients who did not improve. CONCLUSIONS: An explanation for the moderate effect might be that during CBGT, rest and relaxation were too much emphasised. Furthermore, an unselected group of CFS patients and therapists inexperienced in CB(G)T for CFS participated. Suggestions to improve CBGT for future research are given.

Stulemeijer M, de Jong LW, Fiselier TJ, Hoogveld SW, Bleijenberg G. · Expert Centre Chronic Fatigue, University Medical Centre Nijmegen, PO Box 9101, 6500 HB, Netherlands. · BMJ. · Pubmed #15585538 links to  free full text

Abstract: OBJECTIVE: To evaluate the efficacy of cognitive behaviour therapy for adolescents aged 10-17 years with chronic fatigue syndrome. DESIGN: Randomised controlled trial. SETTING: Department of child psychology. PARTICIPANTS: 71 consecutively referred patients with chronic fatigue syndrome; 36 were randomly assigned to immediate cognitive behaviour therapy and 35 to the waiting list for therapy. INTERVENTION: 10 sessions of therapy over five months. Treatment protocols depended on the type of activity pattern (relatively active or passive). All participants were assessed again after five months. MAIN OUTCOME MEASURES: Fatigue severity (checklist individual strength), functional impairment (SF-36 physical functioning), and school attendance. RESULTS: 62 patients had complete data at five months (29 in the immediate therapy group and 33 on the waiting list). Patients in the therapy group reported significantly greater decrease in fatigue severity (difference in decrease on checklist individual strength was 14.5, 95% confidence interval 7.4 to 21.6) and functional impairment (difference in increase on SF-36 physical functioning was 17.3, 6.2 to 28.4) and their attendance at school increased significantly (difference in increase in percentage school attendance was 18.2, 0.8 to 35.5). They also reported a significant reduction in several accompanying symptoms. Self reported improvement was largest in the therapy group. CONCLUSION: Cognitive behaviour therapy is an effective treatment for chronic fatigue syndrome in adolescents.

Prins JB, Bos E, Huibers MJ, Servaes P, van der Werf SP, van der Meer JW, Bleijenberg G. · Department of Medical Psychology, University Medical Centre Nijmegen, Nijmegen, The Netherlands. · Psychother Psychosom. · Pubmed #15031590 No free full text.

Abstract: BACKGROUND: Several studies suggested that the surroundings of chronic fatigue syndrome (CFS) patients are of importance in the persistence of complaints. Contrary to what was expected, participation in support groups has not led to clinical improvement. The purpose of the present study was to describe social support in CFS patients as compared with other fatigued and non-fatigued groups. Further, changes in social support and the influence of social support on the course of CFS over a period of more than 1 year were studied in patients with and without treatment. METHODS: Baseline data were assessed in 270 CFS patients, 150 disease-free breast cancer patients, 151 fatigued employees on sick-leave and 108 healthy subjects using the Social Support List and Significant Others Scale. CFS patients were followed in cognitive behaviour therapy (CBT), guided support groups and natural course at 8 and 14 months. RESULTS: CFS patients and fatigued employees reported more negative interactions and insufficiency of supporting interactions than cancer patients and healthy controls. No differences in frequency of supporting interactions were found. Negative interactions decreased significantly after treatment with CBT, but did not change in support groups or natural course. In the natural course, higher fatigue severity at 8 months was predicted by more negative interactions at baseline. CONCLUSIONS: In CFS patients and fatigued employees, social support is worse than in disease-free cancer patients and healthy controls. Lack of social support was identified as a new factor in the model of perpetuating factors of fatigue severity and functional impairment in CFS.

Ohashi K, Bleijenberg G, van der Werf S, Prins J, Amaral LA, Natelson BH, Yamamoto Y. · Educational Physiology Laboratory, Graduate School of Education, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. · Methods Inf Med. · Pubmed #15026831 No free full text.

Abstract: OBJECTIVES: Our objectives were to study the temporal correlation of physical activity time series in patients with chronic fatigue syndrome (CFS) during normal daily life and to examine if it could identify the altered physical activity in these patients. METHODS: Fractal scaling exponents of diurnal and nocturnal physical activity time series in 10 CFS patients and 6 healthy control subjects (CON) were calculated by the detrended fluctuation analysis (DFA) and the wavelet transform modulus maxima (WTMM) method. We hypothesized that, due to their illness- and/or fatigue-induced resting episodes, altered physical activity patterns in CFS patients might be observed at the interruption of activity bursts. Thus, we further developed a new method, the wavelet transform negative modulus maxima (WTNMM) method, which could evaluate the temporal correlation at the interruption of activities. We compared the fractal scaling exponents for CFS and CON by each method. RESULTS: Both for CFS and CON, we found the fractal time structures in their diurnal physical activity records for at least up to 35 minutes. No group difference was found in nocturnal activities. The WTNMM method revealed that, in diurnal activities, CFS patients had significantly (p < 0.01) smaller fractal scaling exponent (0.87 +/- 0.03) compared to controls (1.01 +/- 0.03). Such a difference was identified neither by the DFA nor WTMM method. CONCLUSIONS: CFS patients had more abrupt interruptions of voluntary physical activity during diurnal periods in normal daily life, probed by the decreased correlation in the negative modulus maxima of the wavelet-transformed activity data, possibly due to their exaggerated fatigue.

Huibers MJ, Beurskens AJ, Van Schayck CP, Bazelmans E, Metsemakers JF, Knottnerus JA, Bleijenberg G. · Department of Epidemiology, Maastricht University, The Netherlands. · Br J Psychiatry. · Pubmed #14990522 links to  free full text

Abstract: BACKGROUND: Fatigue is a common complaint that may lead to long-term sick leave and work disability. AIMS: To assess the efficacy of cognitive-behavioural therapy by general practitioners for unexplained, persistent fatigue among employees. METHOD: A randomised controlled trial, using a pre-randomisation design in primary care, investigated 151 employees on sick leave with fatigue. Participants in the experimental group were offered five to seven 30 min sessions of cognitive-behavioural therapy by a general practitioner; those in the control group were offered no treatment. Main outcome measures (fatigue severity, self-reported absenteeism, registered absenteeism and clinical recovery) were assessed at 4 months, 8 months and 12 months. RESULTS: At baseline, 44% of the patients already met research criteria for chronic fatigue syndrome. There was no significant difference between the experimental group and the control group on primary or secondary outcomes at any point. CONCLUSIONS: Cognitive-behavioural therapy by general practitioners for unexplained, persistent fatigue did not prove to be an effective intervention. Since these doctors were unable to deliver this therapy effectively under ideal circumstances, it is unlikely that doctors in routine practice would be more successful in doing so.

Severens JL, Prins JB, van der Wilt GJ, van der Meer JW, Bleijenberg G. · Department of Medical Technology Assessment, University Medical Centre Nijmegen, The Netherlands. · QJM. · Pubmed #14976272 links to  free full text

Abstract: BACKGROUND: There is some evidence that cognitive behaviour therapy (CBT) is efficacious in chronic fatigue syndrome (CFS), but little data on its cost-effectiveness. DESIGN: Prospective economic analysis alongside a randomized clinical trial. METHODS: CFS patients were randomly assigned to CBT, guided support groups (SG), or the 'natural course' (NC, no protocol-based interventions). Patients were treated for 8 months and followed-up for another 6 months. Costs per patient showing clinically significant improvement, based on the CIS fatigue scale, and costs per quality-adjusted life year, were determined for a time period of 14 months. RESULTS: Data were available for 171 patients at 8 months and for 128 at 14 months. At 8 and 14 months, the percentages of improved patients were 31% and 27% for CBT, 9% and 11% for SG, and 12% and 20% for NC. Mean QALYs gained at 14 months were, for CBT, SG and NC, respectively, 0.0737, -0.0018 and 0.0458. CBT and SG mean treatment costs were euro1490 and euro424. Other medical costs for CBT, SG, and NC, respectively, were euro324, euro623 and euro412 for the first period, and euro232, euro561 and euro378 for the second period. Non-medical costs for these periods for CBT, SG and NC were euro262, euro550, euro427 and euro226, euro439, euro287, respectively. Productivity costs were considerable, but not significantly different between groups. DISCUSSION: CBT was less costly and more effective than SG. Compared to NC, the baseline incremental cost-effectiveness of CBT was euro20 516 per CFS patient showing clinically significant improvement, and euro21 375 per QALY. The bootstrap ratios showed considerable uncertainty regarding the results. Future research should focus on productivity costs, and follow patients prospectively over a longer period.

The GK, Prins J, Bleijenberg G, van der Meer JW. · University Medical Centre Nijmegen, Department of Internal Medicine, PO Box 9101, 6500 HB Nijmegen, The Netherlands. · Neth J Med. · Pubmed #14692441 links to  free full text

Abstract: OBJECTIVE: To explore the effect of granisetron, a 5-HT3 antagonist, on fatigue and functional impairment in patients with chronic fatigue syndrome (CFS). METHODS: Five female patients were eligible to receive oral granisetron for one month (1 mg a day for the first two weeks and 2 mg a day for the second two weeks). The patients had to be between 18 and 65 years of age and suffering from CFS according to the CDC criteria. The effect was assessed by pre- and post-testing, using validated instruments designed to assess the different dimensions of CFS. Treatment response was also evaluated by visual analogue scales (VAS) for fatigue. Analysis was based on intention to treat. RESULTS: Treatment with granisetron resulted in significant improvement in fatigue severity and functional impairment. Activity level showed no significant increase. CONCLUSION: The promising results of this study have encouraged us to perform a placebo-controlled, double-blind study to evaluate the efficacy of 5-HT3 receptor antagonists in the treatment of CFS.

Brouwers FM, Van Der Werf S, Bleijenberg G, Van Der Zee L, Van Der Meer JW. · Departments of. General Internal Medicine and. Medical Psychology, University Medical Center Nijmegen, The Netherlands. · QJM. · Pubmed #12324640 links to  free full text

Abstract: BACKGROUND:The efficacy of dietary supplements in chronic fatigue syndrome (CFS) is uncertain, with conflicting evidence. Aim: To assess the effect of a polynutrient supplement on fatigue and physical activity of patients with CFS. DESIGN:Prospective randomized placebo-controlled, double-blind trial. METHODS:Fifty-three patients (16 males, 37 females) fulfilling the CDC criteria of CFS. The entry criteria were a score on the Checklist Individual Strength subscale fatigue severity (CIS fatigue) >or=40 and a weighted sum score of >or=750 for the eight subscales of the Sickness Impact Profile (SIP8) and no use of nutritional supplements in the 4 weeks prior to entry. The exclusion criteria were pregnancy and lactose intolerance. The intervention-a polynutrient supplement containing several vitamins, minerals and (co)enzymes, or placebo, twice daily for 10 weeks-was preceded by 2 weeks of baseline measurements. Outcome measurements took place in week 9 and 10 of the intervention. Five participants dropped out (4 supplement, 1 placebo). The main outcome measures were CIS fatigue score, number of CDC symptoms and SIP8 score. Efficacy analyses were performed on an intention-to-treat basis. RESULTS:No significant differences were found between the placebo and the treated group on any of the outcome measures: CIS fatigue +2.16 (95%CI -4.3 to +4.39, p=0.984); CDC symptoms +0.42 (95%CI -0.61 to +1.46, p=0.417); SIP8 +182 (95%CI -165 to +529, p=0.297). No patient reported full recovery. DISCUSSION:The findings do not support the use of a broad-spectrum nutritional supplement in treating CFS-related symptoms.

Prins JB, Bleijenberg G, Bazelmans E, Elving LD, de Boo TM, Severens JL, van der Wilt GJ, Spinhoven P, van der Meer JW. · Department of Medical Psychology, University Medical Centre, Nijmegen, The Netherlands. · Lancet. · Pubmed #11265953 No free full text.

Abstract: BACKGROUND: Cognitive behaviour therapy (CBT) seems a promising treatment for chronic fatigue syndrome (CFS), but the applicability of this treatment outside specialised settings has been questioned. We compared CBT with guided support groups and the natural course in a randomised trial at three centres. METHODS: Of 476 patients diagnosed with CFS, 278 were eligible and willing to take part. 93 were randomly assigned CBT (administered by 13 therapists recently trained in this technique for CFS), 94 were assigned the support-group approach, and 91 the control natural course. Multidimensional assessments were done at baseline, 8 months, and 14 months. The primary outcome variables were fatigue severity (on the checklist individual strength) and functional impairment (on the sickness impact profile) at 8 and 14 months. Data were analysed by intention to treat. FINDINGS: 241 patients had complete data (83 CBT, 80 support groups, 78 natural course) at 8 months. At 14 months CBT was significantly more effective than both control conditions for fatigue severity (CBT vs support groups 5.8 [2.2-9.4]; CBT vs natural course 5.6 [2.1-9.0]) and for functional impairment (CBT vs support groups 263 [38-488]; CBT vs natural course 222 [3-441]). Support groups were not more effective for CFS patients than the natural course. Among the CBT group, clinically significant improvement was seen in fatigue severity for 20 of 58 (35%), in Karnofsky performance status for 28 of 57 (49%), and self-rated improvement for 29 of 58 (50%). Prognostic factors for outcome after CBT were a higher sense of control predicting more improvement, and a passive activity pattern and focusing on bodily symptoms predicting less improvement. INTERPRETATION: CBT was more effective than guided support groups and the natural course in a multicentre trial with many therapists. Our study showed a lower proportion of patients with improvement than CBT trials with a few highly skilled therapists.

van der Werf SP, Prins JB, Vercoulen JH, van der Meer JW, Bleijenberg G. · The Netherlands Fatigue Research Group Nijmegen, Department of Medical Psychology and Internal Medicine, University Hospital Nijmegen, Post Box 9101, 6500 HB, Nijmegen, The Netherlands. · J Psychosom Res. · Pubmed #11164063 No free full text.

Abstract: OBJECTIVE: Changes in physical activity are thought to play an important role in maintaining symptoms in chronic fatigue syndrome (CFS). The aim of this study was to describe intraindividual physical activity patterns in more detail and to identify pervasively passive patients. METHODS: With help of a movement-sensing device, physical activity levels were registered continuously over a 12-day period in 277 CFS patients. Within this registration period, the 10 largest activity peaks were computed. The intensity and duration of these activity peaks and their subsequent rest periods were described and compared to those of 47 healthy controls. In addition, the patients' 12 daily activity scores were used to identify patients who were characterised by low levels of physical activity throughout the registration period. RESULTS: The CFS sample had less intense and shorter activity peaks, while the average rest periods that followed these peaks lasted longer. Approximately one-fourth of the CFS sample differed distinctly from the control group and was labelled as pervasively passive. CONCLUSION: The measurements and classification of actual physical activity levels were found to reduce heterogeneity in the CFS population and therefore could provide the opportunity to optimise behavioural intervention protocols for CFS.

Burton C, Knoop H, Popovic N, Sharpe M, Bleijenberg G. · Division of Community Health Sciences, General Practice Section, University of Edinburgh, West Richmond Street, Edinburgh, UK. · Biopsychosoc Med. · Pubmed #19490619 links to  free full text

Abstract: ABSTRACT: BACKGROUND: Chronic fatigue syndrome (CFS) is an illness characterised by pervasive physical and mental fatigue without specific identified pathological changes. Many patients with CFS show reduced physical activity which, though quantifiable, has yielded little information to date. Nonlinear dynamic analysis of physiological data can be used to measure complexity in terms of dissimilarity within timescales and similarity across timescales. A reduction in these objective measures has been associated with disease and ageing. We aimed to test the hypothesis that activity patterns of patients with CFS would show reduced complexity compared to healthy controls. METHODS: We analysed continuous activity data over 12 days from 42 patients with CFS and 21 matched healthy controls. We estimated complexity in two ways, measuring dissimilarity within timescales by calculating entropy after a symbolic dynamic transformation of the data and similarity across timescales by calculating the fractal dimension using allometric aggregation. RESULTS: CFS cases showed reduced complexity compared to controls, as evidenced by reduced dissimilarity within timescales (mean (SD) Renyi(3) entropy 4.05 (0.21) vs. 4.30 (0.09), t = -6.6, p < 0.001) and reduced similarity across timescales (fractal dimension 1.19 (0.04) vs. 1.14 (0.04), t = 4.2, p < 0.001). This reduction in complexity persisted after adjustment for total activity. CONCLUSION: Patients with CFS show evidence of reduced complexity of activity patterns. Measures of complexity applied to activity have potential value as objective indicators for CFS.

Scheeres K, Knoop H, Meer J, Bleijenberg G. · Expert Centre Chronic Fatigue, Radboud University Nijmegen Medical Centre (4628), PO Box 9101, 6500 HB Nijmegen, The Netherlands. · Health Qual Life Outcomes. · Pubmed #19338668 links to  free full text

Abstract: BACKGROUND: Effective treatment of chronic fatigue syndrome (CFS) with cognitive behavioural therapy (CBT) relies on a correct classification of so called 'fluctuating active' versus 'passive' patients. For successful treatment with CBT is it especially important to recognise the passive patients and give them a tailored treatment protocol. In the present study it was evaluated whether CFS patient's physical activity pattern can be assessed most accurately with the 'Activity Pattern Interview' (API), the International Physical Activity Questionnaire (IPAQ) or the CFS-Activity Questionnaire (CFS-AQ). METHODS: The three instruments were validated compared to actometers. Actometers are until now the best and most objective instrument to measure physical activity, but they are too expensive and time consuming for most clinical practice settings. In total 226 CFS patients enrolled for CBT therapy answered the API at intake and filled in the two questionnaires. Directly after intake they wore the actometer for two weeks. Based on receiver operating characteristic (ROC) curves the validity of the three methods were assessed and compared. RESULTS: Both the API and the two questionnaires had an acceptable validity (0.64 to 0.71). None of the three instruments was significantly better than the others. The proportion of false predictions was rather high for all three instrument. The IPAQ had the highest proportion of correct passive predictions (sensitivity 70.1%). CONCLUSION: The validity of all three instruments appeared to be fair, and all showed rather high proportions of false classifications. Hence in fact none of the tested instruments could really be called satisfactory. Because the IPAQ showed to be the best in correctly predicting 'passive' CFS patients, which is most essentially related to treatment results, it was concluded that the IPAQ is the preferable alternative for an actometer when treating CFS patients in clinical practice.

Goedendorp MM, Knoop H, Schippers GM, Bleijenberg G. · Expert Centre for Chronic Fatigue, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. · J Hum Nutr Diet. · Pubmed #19226353 No free full text.

Abstract: BACKGROUND: Little is known about the lifestyle of patients with chronic fatigue syndrome (CFS) and its influence on symptoms of CFS. The present study aimed to investigate the lifestyle of patients with CFS, and to assess whether lifestyle factors are related to fatigue and functional impairments. METHODS: Two hundred and forty-seven patients fulfilling the Center for Disease Control criteria for CFS were included. Validated questionnaires were used to collect data on lifestyle factors, smoking, intake of alcohol, fat, fibres, fruit and vegetables, body mass index (BMI), fatigue severity and functional impairments. RESULTS: Of the CFS patients, 23% smoked, 32% had an unhealthy BMI, and none had an unhealthy alcohol intake. A majority had an unhealthy food intake: 70% had unhealthy fat, fruit and vegetable intake, and 95% had unhealthy fibre intake. Compared with the general Dutch population, significantly fewer CFS patients were overweight. Significantly more female CFS patients abstained from alcohol, and fewer male CFS patients smoked. Unhealthy lifestyle factors were not significantly associated with fatigue severity or functional impairments. CONCLUSIONS: CFS patients tend to lead a healthier lifestyle compared to the general Dutch population. However, no relationship was found between lifestyle factors and fatigue severity and functional impairments in CFS.

Knoop H, van der Meer JW, Bleijenberg G. · Expert Centre Chronic Fatigue, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. · Br J Psychiatry. · Pubmed #18827302 No free full text.

Abstract: A minimal intervention, based on cognitive-behavioural therapy for chronic fatigue syndrome and consisting of self-instructions combined with email contact, was tested in a randomised controlled trial (ISRCTN27293439). A total of 171 patients participated in the trial: 85 were allocated to the intervention condition and 86 to the waiting-list condition. All patients met the Centers for Disease Control and Prevention criteria for chronic fatigue syndrome. An intention-to-treat analysis showed a significant decrease in fatigue and disability after self-instruction. The level of disability was negatively correlated with treatment outcome. Guided self-instructions are an effective treatment for patients with relatively less severe chronic fatigue syndrome.

Scheeres K, Wensing M, Bleijenberg G, Severens JL. · Expert Centre Chronic Fatigue, Radboud University Nijmegen Medical Centre (4628), PO Box 9101, 6500 HB, The Netherlands. · BMC Health Serv Res. · Pubmed #18700975 links to  free full text

Abstract: BACKGROUND: This study investigated the costs and outcomes of implementing cognitive behavior therapy (CBT) for chronic fatigue syndrome (CFS) in a mental health center (MHC). CBT is an evidence-based treatment for CFS that was scarcely available until now. To investigate the possibilities for wider implementation, a pilot implementation project was set up. METHOD: Costs and effects were evaluated in a non-controlled before- and after study with an eight months time-horizon. Both the costs of performing the treatments and the costs of implementing the treatment program were included in the analysis. The implementation interventions included: informing general practitioners (GPs) and CFS patients, training therapists, and instructing the MHC employees. Given the non-controlled design, cost outcome ratios (CORs) and their acceptability curves were analyzed. Analyses were done from a health care perspective and from a societal perspective. Bootstrap analyses were performed to estimate the uncertainty around the cost and outcome results. RESULTS: 125 CFS patients were included in the study. After treatment 37% had recovered from CFS and the mean gained QALY was 0.03. Costs of patients' health care and productivity losses had decreased significantly. From the societal perspective the implementation led to cost savings and to higher health states for patients, indicating dominancy. From the health care perspective the implementation revealed overall costs of 5.320 euros per recovered patient, with an acceptability curve showing a 100% probability for a positive COR at a willingness to pay threshold of 6.500 euros per recovered patient. CONCLUSION: Implementing CBT for CFS in a MHC appeared to have a favorable cost outcome ratio (COR) from a societal perspective. From a health care perspective the COR depended on how much a recovered CFS patient is being valued. The strength of the evidence was limited by the non-controlled design. The outcomes of this study might facilitate health care providers when confronted with the decision whether or not to adopt CBT for CFS in their institution.

Kalkman JS, Zwarts MJ, Schillings ML, van Engelen BG, Bleijenberg G. · Department of Medical Psychology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. · Neurol Sci. · Pubmed #18690504 No free full text.

Abstract: Although fatigue is a common symptom in neuromuscular disorders, little is known about different types of fatigue. Sixty-five FSHD, 79 adult-onset MD and 73 HMSN type I patients were studied. Experienced fatigue was assessed with the CIS-fatigue subscale. Physiological fatigue was measured during a 2-min sustained maximal voluntary contraction of the biceps brachii muscle using the twitch interpolation technique to assess central activation failure (CAF) and peripheral fatigue. Experienced fatigue, CAF and peripheral fatigue appeared to be predominantly separate types of fatigue.

de Lange FP, Koers A, Kalkman JS, Bleijenberg G, Hagoort P, van der Meer JW, Toni I. · F.C. Donders Centre for Cognitive Neuroimaging, Radboud University Nijmegen, Kapittelweg 29, 6500 HB Nijmegen, The Netherlands. · Brain. · Pubmed #18587150 links to  free full text

Abstract: Chronic fatigue syndrome (CFS) is a disabling disorder, characterized by persistent or relapsing fatigue. Recent studies have detected a decrease in cortical grey matter volume in patients with CFS, but it is unclear whether this cerebral atrophy constitutes a cause or a consequence of the disease. Cognitive behavioural therapy (CBT) is an effective behavioural intervention for CFS, which combines a rehabilitative approach of a graded increase in physical activity with a psychological approach that addresses thoughts and beliefs about CFS which may impair recovery. Here, we test the hypothesis that cerebral atrophy may be a reversible state that can ameliorate with successful CBT. We have quantified cerebral structural changes in 22 CFS patients that underwent CBT and 22 healthy control participants. At baseline, CFS patients had significantly lower grey matter volume than healthy control participants. CBT intervention led to a significant improvement in health status, physical activity and cognitive performance. Crucially, CFS patients showed a significant increase in grey matter volume, localized in the lateral prefrontal cortex. This change in cerebral volume was related to improvements in cognitive speed in the CFS patients. Our findings indicate that the cerebral atrophy associated with CFS is partially reversed after effective CBT. This result provides an example of macroscopic cortical plasticity in the adult human brain, demonstrating a surprisingly dynamic relation between behavioural state and cerebral anatomy. Furthermore, our results reveal a possible neurobiological substrate of psychotherapeutic treatment.

Scheeres K, Wensing M, Severens H, Adang E, Bleijenberg G. · Expert Centre Chronic Fatigue, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. · J Psychosom Res. · Pubmed #18582610 No free full text.

Abstract: BACKGROUND: Chronic fatigue syndrome (CFS) is associated with a high use of health care services. To reduce the related costs for patients and society, it will be useful to know which factors determine CFS patients' amount of health care use. Little is known, however, about these factors. METHOD: The present study retrospectively performed a cross-sectional analysis to investigate the possible factors determining CFS patients' health care use. A total of 263 CFS patients, derived from two subgroups (149 from tertiary care and 114 from primary/secondary care), participated. Health care use was measured with a questionnaire asking details on consumption over the past 6 months. Fatigue severity and physical functioning were measured with the subscale Experienced Fatigue of the Checklist Individual Strength (CIS-20) and the subscale Physical Functioning of the SF-36, respectively. Multiple regression analysis, T-tests, and chi(2) tests were performed. RESULTS: The regression analysis revealed that, after controlling for patient characteristics (explaining 13%), fatigue factors added 4% predictive value and certain perpetuating factors of fatigue, including focus on bodily symptoms and attributions of fatigue, added another 5%. The analysis of subgroups revealed that, compared to the tertiary care population, fewer patients from primary/secondary care had visited a medical specialist (50% vs. 71%), used antidepressants (16% vs. 25%) and tranquilizers (3% vs. 18%), and had spent a night in hospital (7% vs. 10%). However, overall costs of health care between these subgroups did not differ. CONCLUSIONS: This study showed that illness duration, physical impairment due to fatigue, and psychological perpetuating factors of fatigue do determine the variance in CFS patients' health care use. These results give clear directions for treating CFS patients and managing health care for CFS.

Knoop H, Stulemeijer M, de Jong LW, Fiselier TJ, Bleijenberg G. · Expert Centre Chronic Fatigue, Radboud University, Nijmegen Medical Centre, Postbox 9011, 6525 EC Nijmegen, The Netherlands. · Pediatrics. · Pubmed #18310181 links to  free full text

Abstract: OBJECTIVES: The purpose of this work was to assess the long-term outcome of adolescents with chronic fatigue syndrome who received cognitive behavioral therapy and to determine the predictive value of fatigue severity and physical impairments of the adolescent and the fatigue severity of the mother at baseline for the outcome of the treatment at follow-up. PATIENTS AND METHODS: Sixty-six adolescent patients with chronic fatigue syndrome who previously participated in a randomized, controlled trial that showed that cognitive behavioral therapy was more effective than a waiting-list condition in reducing fatigue and improving physical functioning were contacted for a follow-up assessment. Fifty participants of the follow-up study had received cognitive behavioral therapy for chronic fatigue syndrome (32 formed the cognitive behavioral therapy group in the original trial, and 18 patients received cognitive behavioral therapy after the waiting period). The remaining 16 patients had refused cognitive behavioral therapy after the waiting period. The main outcome measures were fatigue severity (Checklist Individual Strength), physical functioning (Short-Form General Health Survey), and school attendance. RESULTS: Data were complete for 61 patients at follow-up (cognitive behavioral therapy group: 47 patients; no-treatment group: 14 patients). The mean follow-up time was 2.1 years. There was no significant change in fatigue severity between posttreatment and follow-up in the cognitive behavioral therapy group. There was a significant further increase in physical functioning and school attendance (10% increase). The adolescents in the cognitive behavioral therapy group were significantly less fatigued and significantly less functionally impaired and had higher school attendance at follow-up than those in the no-treatment group. Fatigue severity of the mother was a significant predictor of treatment outcome. CONCLUSIONS: The positive effects of cognitive behavioral therapy in adolescents with chronic fatigue syndrome are sustained after cognitive behavioral therapy. Higher fatigue severity of the mother predicts lower treatment outcome in adolescent patients.