BMJ Open, 1 June 2013.
Are there sleep-specific phenotypes in patients with chronic fatigue syndrome? A cross-sectional polysomnography analysis
Zoe M Gotts(1), Vincent Deary(1), Julia Newton(2), Donna Van der Dussen(3), Pierre De Roy(3), Jason G Ellis(1)
(1) Northumbria Centre for Sleep Research, Department of Psychology, Northumbria University, Newcastle, UK
(2) Institute for Ageing and Health, Newcastle University, Newcastle, UK
(3) Fatigue Service, VermoeidheidCentrum Nederland bv, Lelystad, The Netherlands
Correspondence to Dr Jason G Ellis; Jason.firstname.lastname@example.org
Despite sleep disturbances being a central complaint in patients with chronic fatigue syndrome (CFS), evidence of objective sleep abnormalities from over 30 studies is inconsistent. The present study aimed to identify whether sleep-specific phenotypes exist in CFS and explore objective characteristics that could differentiate phenotypes, while also being relevant to routine clinical practice.
DESIGN A cross-sectional, single-site study.
SETTING A fatigue clinic in the Netherlands.
A consecutive series of 343 patients meeting the criteria for CFS, according to the Fukuda definition.
Patients underwent a single night of polysomnography (all-night recording of EEG, electromyography, electrooculography, ECG and respiration) that was hand-scored by a researcher blind to diagnosis and patient history.
Of the 343 patients, 104 (30.3%) were identified with a Primary Sleep Disorder explaining their diagnosis.
A hierarchical cluster analysis on the remaining 239 patients resulted in four sleep phenotypes being identified at saturation. Of the 239 patients, 89.1% met quantitative criteria for at least one objective sleep problem. A one-way analysis of variance confirmed distinct sleep profiles for each sleep phenotype.
Relatively longer sleep onset latencies, longer Rapid Eye Movement (REM) latencies and smaller percentages of both stage 2 and REM characterised the first phenotype. The second phenotype was characterised by more frequent arousals per hour. The third phenotype was characterised by a longer Total Sleep Time, shorter REM Latencies, and a higher percentage of REM and lower percentage of wake time. The final phenotype had the shortest Total Sleep Time and the highest percentage of wake time and wake after
The results highlight the need to routinely screen for Primary Sleep Disorders in clinical practice and tailor sleep interventions, based on phenotype, to patients presenting with CFS. The results are discussed in terms of matching patients’ self-reported sleep to these phenotypes in clinical practice.
From Research Developments in Primary Care, 25 April 2013. (Epub ahead of print).
Adolescents and mothers value referral to a specialist service for chronic fatigue syndrome or myalgic encephalopathy (CFS/ME).
Beasant L, Mills N, Crawley E.
School of Social & Community Medicine, Centre for Child & Adolescent Health, University of Bristol, Oakfield Grove, UK.
Paediatric chronic fatigue syndrome or myalgic encephalopathy (CFS/ME) is relatively common and disabling. Current guidance recommends referral to specialist services, although some general practitioners believe the label of CFS/ME is harmful and many are not confident about diagnosing CFS/ME. Aim Explore whether or not adolescents and their mothers value referral to a specialist service for young people with CFS/ME.
A qualitative study nested within a feasibility study of interventions for CFS/ME [Specialist Medical Intervention and Lightning Evaluation (SMILE)]. In-depth interviews were undertaken with 13 mothers and 12 adolescents participating in the SMILE study. Transcripts were systematically assigned codes using the qualitative data organisation package NVivo and analysed thematically using techniques of constant comparison.
Gaining access to the specialist service was difficult and took a long time. Mothers felt that they needed to be proactive and persistent, partly because of a lack of knowledge in primary and secondary care. Having gained access, mothers felt the CFS/ME service was useful because it recognised and acknowledged their child's condition and opened channels of dialogue between health-care professionals and education providers. Adolescents reported that specialist medical care resulted in better symptom management, although some adolescents did not like the fact that the treatment approach limited activity.
Adolescents and their mothers value receiving a diagnosis from a specialist service and making progress in managing CFS/ME. General practitioners should support adolescents with CFS/ME in accessing CFS/ME specialist services, consistent with current guidance.
From Frontiers in Physiology, 20 May 2013.
Brain dysfunction as one cause of CFS symptoms including difficulty with attention and concentration.
Director, Pain and Fatigue Study Center, Department of Pain Medicine and Palliative Care, Beth Israel Medical Center, Manhattan New York, NY, USA ; Professor of Neurology, Albert Einstein College of Medicine, Bronx New York, NY, USA.
We have been able to reduce substantially patient pool heterogeneity by identifying phenotypic markers that allow the researcher to stratify chronic fatigue syndrome (CFS) patients into subgroups.
To date, we have shown that stratifying based on the presence or absence of comorbid psychiatric diagnosis leads to a group with evidence of neurological dysfunction across a number of spheres. We have also found that stratifying based on the presence or absence of comorbid fibromyalgia leads to information that would not have been found on analyzing the entire, unstratified patient group.
Objective evidence of orthostatic intolerance (OI) may be another important variable for stratification and may define a group with episodic cerebral hypoxia leading to symptoms.
We hope that this review will encourage other researchers to collect data on discrete phenotypes in CFS to allow this work to continue more broadly.
Finding subgroups of CFS suggests different underlying pathophysiological processes responsible for the symptoms seen. Understanding those processes is the first step toward developing discrete treatments for each.
From Antioxidants and Redox Signalling, 29 May 2013. [Epub ahead of print].
Could Mitochondrial Dysfunction Be a Differentiating Marker Between Chronic Fatigue Syndrome and Fibromyalgia?
Castro-Marrero J, Cordero MD, Sáez-Francas N, Jimenez-Gutierrez C, Aguilar-Montilla FJ, Aliste L, Alegre-Martin J.
CFS Unit, Institut de Recerca Vall d'Hebron, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Abstract Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are complex and serious illnesses that affect approximately 2.5% and 5% of the general population worldwide, respectively. The etiology is unknown; however, recent studies suggest that mitochondrial dysfunction has been involved in the pathophysiology of both conditions.
We have investigated the possible association between mitochondrial biogenesis and oxidative stress in patients with CFS and FM. We studied 23 CFS patients, 20 FM patients, and 15 healthy controls.
Peripheral blood mononuclear cell showed decreased levels of Coenzyme Q10 from CFS patients (p<0.001 compared with controls) and from FM subjects (p<0.001 compared with controls) and ATP levels for CFS patients (p<0.001 compared with controls) and for FM subjects (p<0.001 compared with controls). On the contrary, CFS/FM patients had significantly increased levels of lipid peroxidation, respectively (p<0.001 for both CFS and FM patients with regard to controls) that were indicative of oxidative stress-induced damage. Mitochondrial citrate synthase activity was significantly lower in FM patients (p<0.001) and, however, in CFS, it resulted in similar levels than controls. Mitochondrial DNA content (mtDNA/gDNA ratio) was normal in CFS and reduced in FM patients versus healthy controls, respectively (p<0.001). Expression levels of peroxisome proliferator-activated receptor gamma-coactivator 1-alpha and transcription factor A, mitochondrial by immunoblotting were significantly lower in FM patients (p<0.001) and were normal in CFS subjects compared with healthy controls. These data lead to the hypothesis that mitochondrial dysfunction-dependent events could be a marker of differentiation between CFS and FM, indicating the mitochondria as a new potential therapeutic target for these conditions.
From Disability and Rehabilitation, 4 June 2013 [Epub ahead of print]
Use of an online survey to explore positive and negative outcomes of rehabilitation for people with CFS/ME.
Gladwell PW, Pheby D, Rodriguez T, Poland F.
North Bristol NHS Trust , Bristol , UK .
First, to explore the experiences of people with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) of rehabilitation therapies so as to build an understanding of reasons
for the discrepancy between the notably mixed experiences regarding effectiveness reported in patient surveys and the RCT evidence about the efficacy of Graded Exercise Therapy (GET). GET is a form of structured and supervised activity management that aims for gradual but progressive increases in physical activity. Second, to review patient experiences of two related rehabilitation approaches, Exercise on Prescription (EoP) and Graded Activity Therapy (GAT).
An online survey conducted by the charity Action for ME generated qualitative data about 76 patient experiences of rehabilitation undertaken during or after 2008, examined using thematic analysis.
Both positive and negative experiences of rehabilitation were reported. Positive themes included supportive communication, the benefits of a routine linked with baseline setting and pacing, the
value of goal setting, and increasing confidence associated with exercise. Negative themes included poor communication, feeling pushed to exercise beyond a sustainable level, having no setback plan, and patients feeling blamed for rehabilitation not working.
The negative themes may help explain the negative outcomes from rehabilitation reported by previous patient surveys. The negative themes indicate rehabilitation processes which contradict the
NICE (National Institute for Health and Clinical Excellence) Guideline advice regarding GET, indicating that some clinical encounters were not implementing these. These findings suggest areas for improving therapist training, and for developing quality criteria for rehabilitation in CFS/ME.
IMPLICATIONS FOR REHABILITATION
The insensitive delivery of rehabilitation support for people with CFS/ME can explain negative outcomes reported in patient surveys. Therapist-patient collaboration, establishing a sustainable baseline and agreeing a setback plan are all examples of higher quality rehabilitation indicated by this research.
Greater awareness of the positive and negative experiences of rehabilitation therapies should enable avoidance of the potential pitfalls identified in this research.
Positive experiences of rehabilitation therapies include supportive communication with a therapist, treatment which included routines and goals, and value attached to baselines and controlled pacing. By contrast, factors leading to negative experiences include poor communication and support, conflict in beliefs about CFS/ME and rehabilitation, pressure to comply with treatment, worsening of symptoms, baselines experienced as unsustainable, and feeling blamed for rehabilitation not working.