Zoe Gotts

Are there sleep-specific phenotypes in patients with chronic fatigue syndrome? A cross-sectional polysomnography analysis

Objectives 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. Participants A consecutive series of 343 patients meeting the criteria for CFS, according to the Fukuda definition. Measures 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. Results 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 sleep onset. Conclusions 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.

The association between daytime napping and cognitive functioning in chronic fatigue syndrome.

Objectives The precise relationship between sleep and physical and mental functioning in chronic fatigue syndrome (CFS) has not been examined directly, nor has the impact of daytime napping. This study aimed to examine self-reported sleep in patients with CFS and explore whether sleep quality and daytime napping, specific patient characteristics (gender, illness length) and levels of anxiety and depression, predicted daytime fatigue severity, levels of daytime sleepiness and cognitive functioning, all key dimensions of the illness experience. Methods 118 adults meeting the 1994 CDC case criteria for CFS completed a standardised sleep diary over 14 days. Momentary functional assessments of fatigue, sleepiness, cognition and mood were completed by patients as part of usual care. Levels of daytime functioning and disability were quantified using symptom assessment tools, measuring fatigue (Chalder Fatigue Scale), sleepiness (Epworth Sleepiness Scale), cognitive functioning (Trail Making Test, Cognitive Failures Questionnaire), and mood (Hospital Anxiety and Depression Scale). Results Hierarchical Regressions demonstrated that a shorter time since diagnosis, higher depression and longer wake time after sleep onset predicted 23.4% of the variance in fatigue severity (p <.001). Being male, higher depression and more afternoon naps predicted 25.6% of the variance in objective cognitive dysfunction (p <.001). Higher anxiety and depression and morning napping predicted 32.2% of the variance in subjective cognitive dysfunction (p <.001). When patients were classified into groups of mild and moderate sleepiness, those with longer daytime naps, those who mainly napped in the afternoon, and those with higher levels of anxiety, were more likely to be in the moderately sleepy group. Conclusions Napping, particularly in the afternoon is associated with poorer cognitive functioning and more daytime sleepiness in CFS. These findings have clinical implications for symptom management strategies.

A concept mapping study evaluating the UK's first NHS generic fatigue clinic

Fatigue is a significant and debilitating symptom affecting 25% of the population. It occurs in those with a range of chronic diseases, can be idiopathic and in 0.2–0.4% of the UK population occurs in combination with other symptoms that together constitute chronic fatigue syndrome (CFS). Until recently, NHS clinical services only focussed upon CFS and excluded the majority of fatigued patients who did not meet the CFS diagnostic criteria. The CRESTA Fatigue interdisciplinary clinic was established in 2013 in response to this unmet need.

An investigation into the prevalence of sleep disturbances in primary Sjögren’s syndrome: a systematic review of the literature

Objectives. To identify whether sleep disturbances are more prevalent in primary SS (pSS) patients compared with the general population and to recognize which specific sleep symptoms are particularly problematic in this population. Methods. Electronic searches of the literature were conducted in PubMed, Medline (Ovid), Embase (Ovid), PsychINFO (Ovid) and Web of Science and the search strategy registered a priori. Titles and abstracts were reviewed by two authors independently against a set of prespecified inclusion/exclusion criteria, reference lists were examined and a narrative synthesis of the included articles was conducted. Results. Eight whole‐text papers containing nine separate studies met the inclusion criteria and were included in the narrative analysis. Few of these studies met all of the quality assessment criteria. The studies used a range of self‐reported measures and objective measures, including polysomnography. Mixed evidence was obtained for some of the individual sleep outcomes, but overall compared with controls, pSS patients reported greater subjective sleep disturbances and daytime somnolence and demonstrated more night awakenings and pre‐existing obstructive sleep apnoea. Conclusions. A range of sleep disturbances are commonly reported in pSS patients. Further polysomnography studies are recommended to confirm the increased prevalence of night awakenings and obstructive sleep apnoea in this patient group. pSS patients with excessive daytime somnolence should be screened for co‐morbid sleep disorders and treated appropriately. Interventions targeted at sleep difficulties in pSS, such as cognitive behavioural therapy for insomnia and nocturnal humidification devices, have the potential to improve quality of life in this patient group and warrant further investigation.

A comparative polysomnography analysis of sleep in healthy controls and patients with chronic fatigue syndrome

ABSTRACT Background: Sleep disturbance affects almost 95% of people with chronic fatigue syndrome (CFS). However, existing studies of sleep in CFS have shown mixed results and methodological issues prevent between-study comparisons. Purpose: To redress this, the present study aimed to investigate whether there are differences in the sleep of patients with CFS and healthy controls, using a comparative analysis of polysomnography over three consecutive nights. Methods: Twenty-two patients with CFS (1994 Centers for Disease Control and Prevention criteria) and 22 healthy controls underwent three nights of polysomnographic sleep assessment. Groups were compared on their objective sleep variables derived from the third night of assessment, to allow for participant adaptation to the sleep study. Results: 9.1% of patients met criteria for an objectively verifiable sleep disorder. Differences in sleep were observed between CFS patients and healthy controls on four objectively derived sleep variables (wake after sleep onset, sleep efficiency, percentage wake and REM Latency). In addition, people with CFS reported more severe symptoms of insomnia than healthy controls. Conclusions: The study reports on key differences in sleep between people with CFS and healthy individuals. The potential presence of a sleep disorder in this patient population is high, it is therefore important that during early evaluation, a detailed history of sleep is taken to rule out a sleep disorder in CFS. In addition, patients with CFS show poorer sleep as defined by objectively derived measures and also self-report poorer quality sleep. Improving sleep is a potential treatment target in CFS.

The role of sleep in chronic fatigue syndrome: a narrative review

Background: Chronic Fatigue Syndrome (CFS) affects 0.23–2.6% of the adult population. Sleep-related complaints are amongst the most frequently reported symptoms in these patients. Although a biopsychosocial model of CFS offers a plausible framework for understanding the condition, the role of sleep and how it functions within this model remains unclear. Purpose: This narrative review describes the findings of studies of sleep in CFS and considers the reasons behind the diversity of results. The review also discusses the difficulties that exist in establishing relationships between sleep, behaviour, cognition, physiology, and the physical symptoms of CFS. Methods: A search of Medline for the terms “CFS,” “chronic fatigue syndrome,” AND “sleep” was performed to identify articles concerning sleep and CFS from 1988 to the present. Results: Subjective sleep dysfunction was frequently reported in the CFS sleep studies. However, objective sleep research in CFS has shown no consistent picture of sleep disturbance, particularly with regard to polysomnography. This may be attributable to the heterogeneity of sleep phenotypes in the CFS population as well as the variability in sleep assessment protocols, case definitions, and exclusion criteria used across studies. Conclusions: Given the high prevalence of disturbed sleep in this population in combination with inconsistent findings, exploration of new protocols for the objective assessment of sleep in CFS (e.g., three-night PSG protocol) is recommended. Understanding the distinct sleep characteristics in this population could serve to improve insight into perpetuating factors of CFS symptoms which is relevant for diagnosis and therapy.

Treatment of insomnia reduces fatigue in chronic fatigue syndrome in those able to comply with the intervention

ABSTRACT Background: Effectiveness of cognitive behavioural therapy for insomnia (CBT-I) has not been explored in Chronic Fatigue Syndrome (CFS), a condition where disturbed sleep is a principal symptom. This study aimed to report feasibility, acceptability and initial effectiveness of CBT-I in CFS. Methods: Sixteen individuals with CFS received face-to-face CBT-I. Treatment comprised six sessions of sleep education, hygiene, restriction, stimulus control and cognitive therapy and completion of daily sleep diaries with an overarching aim to establish regularity in sleep-wake patterns. Patients completed self-report questionnaires (fatigue, pain, mood, sleep preoccupation, insomnia severity, and dysfunctional beliefs about sleep) pre- and post-treatment. Results: Of the seven who completed the intervention five improved on self-reported sleep parameters (diary measures of sleep onset latency, awakenings during the night) following treatment. However, CBT-I was not acceptable for all (56%). Total fatigue (Chalder Fatigue), dropped from mean 22 to 16. Those not able to complete the intervention had higher fatigue, pain, depression and anxiety and reported more severe insomnia at baseline compared to completers. Conclusion: CBT-I is an acceptable non-pharmacological approach with potential to treat sleep disturbances in some CFS patients. Strategies to reduce attrition and increase adherence are necessary, possibly telephone or online sessions, for this group.

Exploration of potential objective and subjective daily indicators of sleep health in normal sleepers

Purpose While the concept of “sleep health” has only recently been defined, how it relates to both subjective and objective sleep parameters is yet to be determined. The current study aimed to identify potential indicators of poorer sleep health, from subjective and objective daily sleep characteristics, in normal sleepers. Participants and methods Eighty-three individuals aged 18–65 years with no history of sleep disorders, chronic physical or psychiatric illnesses, or substance misuse were recruited from the North of England. Secondary analysis of a series of standardized studies, which included psychometrics, actigraphy, and an in-lab polysomnography (PSG) component, was undertaken. Questions from several psychometric sleep scales were combined to create an aggregate measure of sleep health status. Subjective sleep continuity was assessed by 2-week sleep diary. Objective measures comprised two continuous weeks of actigraphy and two nights of in-lab PSG. Results Significant negative correlations were evident between sleep health scores and both diary-derived subjective sleep latency (SL; diary) and actigraphy-derived SL (actigraphy). This was reflected by independent samples t-test between high and low sleep health groups. No relationships between sleep health and PSG parameters were observed. Regression analyses indicated sleep latencies from both the sleep diary and actigraphy as significant predictors, explaining 28.2% of the variance in sleep health. Conclusion Perceived increases in SL appear to be a primary indicator of declining sleep health in normal sleepers. The majority of objective sleep parameters, including gross PSG sleep parameters, appear not to be sensitive to sleep health status in normal sleepers. Future research is needed to understand the physical and psychological correlates of sleep health in larger samples.

Two year follow-up of sleep diaries and polysomnography in chronic fatigue syndrome: a cohort study

ABSTRACT Background: Chronic fatigue syndrome (CFS) is a prevalent and debilitating symptom complex of unknown aetiology. Up to 96.8% of people with CFS report unrefreshing sleep and many describe, in qualitative interviews, changes in sleep over the course of their illness. Purpose: To establish whether subjective and objective sleep parameters change over a two-year follow-up period in patients with CFS. Methods: Twenty-two participants with CFS were recruited during routine consultations at a clinic in the North-East of England. All had their sleep characterised in a previously published cross-sectional study. Two were excluded from this analysis because they fulfilled criteria for a primary sleep disorder. The remaining 20 were contacted and 15 repeated fatigue- and sleep-quality questionnaires and sleep diaries, two years after their sleep was first characterised. Seven participants also repeated two consecutive nights of polysomnography. Paired statistical tests were used to compare follow-up with baseline measures. Results: Subjective questionnaires and sleep dairies did not show differences over two years follow-up. However, polysomnography demonstrated a higher proportion of stage one sleep (P < .01) and more awakenings per hour (P = .04) at follow-up. Conclusions: This study is the first to longitudinally assess sleep parameters in people with CFS. The results suggest that subjective perceptions of sleep remain stable, although objective measures indicated a tendency towards increased periods of lighter sleep. However, the small number of participants increases the likelihood that observed differences are Type I errors.

Objective Improvement in Fatigue Scores for Primary Sjögren’s Patients Receiving a Tailored Multidisciplinary Fatigue Intervention in a Generic Fatigue Clinic

Methods: We recruited 96 participants into the study. Participants with ACR criteria for knee OA were recruited (n=84), who were divided into advanced OA (n=72), who had severe enough disease to require total knee replacement (TKR). Early knee OA subjects had pain but did not require surgery (n=12). An additional 12 controls were recruited to control for pain measures and tissue comparisons from participants undergoing surgery for non-OA reasons. All participants were assessed by Western Ontario and MacMaster Universities Osteoarthritis Index (WOMAC). All subjects had knee MRI to define BML characteristics, synovitis and cartilage damage, scored using the MRI Knee Osteoarthritis Score (MOAKS). Tissue was harvested at TKR for BML analysis using scanning electron microscopy (SEM) and tissue microarray using Illumina. For SEM, tissue blocks were embedded in poly(methyl methacrylate) to give intact tissue and analysed to obtain 3 Dimensional SEM. For microarray, RNA was isolated and reverse transcribed using the Qiagen system, then subjected to microarray using standard Illumina protocols.Background/Purpose: A newly developed and (cross-cultural) validated measurement tool, the computerized Animated Activity Questionnaire (AAQ) for assessing activity limitations in hip and knee osteoarthritis (HKOA) patients, consists of video animations from which patients can choose the animation that best matches their own performance. For application in daily clinical practice as well as in research, the aim of this study was to determine reliability, responsiveness, and interpretability of the AAQ. Methods: First, 238 HKOA patients mixed from hospital and rehabilitation center completed the AAQ twice with 7 days in between. Test-retest reliability (intra-class correlation coefficient (ICC)) the Standard Error of Measurement (SEM), and the Smallest Detectable Change (SDC) were calculated. Second, 92 other patients with hip or knee OA were followed for 6 months in order to assess responsiveness. Patients received conservative physical therapy treatment or joint replacement surgery and were measured before intervention and 6 months later. We hypothesized that change scores on the AAQ (score range 0-100) correlated at least 0.6 with self-report (ADL subscore of the Hip disability and Knee Injury Osteoarthritis Outcome Score,), performance based tests (Timed Up and Go test, Stair Climbing Test, and 30 seconds Chair Stand Test), and a Global Rating of Change (GRC). To estimate the Minimal Important Change (MIC) of the AAQ an anchor-based MIC distribution method was used. The Receiver Operating Characteristic (ROC) method was used to find the optimal AAQ change score that best discriminates. The MIC was compared to the SDC in order to facilitate the interpretation of change scores. Results: ICC for test-retest reliability was 0.93 (95%CI: 0.91-0.95). SEM and SDC were 4.9 and 13.5, respectively. After 6 months the change scores of the AAQ correlated 0.67 with self-reports, 0.47-0.55 with performance based tests, and 0.43 with GRC. The ROC curve showed an area under the curve of 0.71 with a sensitivity of 62% and a specificity of 79% for the optimal MIC of 9.12 for discrimination. The MIC was smaller than the SDC meaning that the change is important but cannot be distinguished from measurement error in individual patients. Conclusion: The AAQ showed good internal consistency, test-retest reliability, and SDC resulting in an average mean score difference of the AAQ over 14% indicating a real improvement in activity limitations in a mix of surgical and conservative HKOA patients. The AAQ is considered responsive, despite the moderate correlations with performancebased tests and GRC, which seems to be caused by the slightly different, new construct the AAQ is measuring with regard to the domain activity limitations.For a searchable version of these abstracts, please visit www.acrabstracts.org.