Received: 8 March 2017 | Revised: 24 June 2017 | Accepted: 10 July 2017 DOI: 10.1111/crj.12667 ORIGINAL ARTICLE Sleep patterns among patients with chronic fatigue: A polysomnography-based study Evelina Pajediene1 | Indre Bileviciute-Ljungar2,3,4 | Danielle Friberg5 1 Department of Neurology, Kaunas Abstract Clinics, Hospital of Lithuanian University of Health Sciences, Kaunas, Lithuania Objectives: The purpose of this study was to detect treatable sleep disorders among 2 Department of Clinical Sciences, patients complaining of chronic fatigue by using sleep questionnaires and Karolinska Institutet, Stockholm, Sweden polysomnography. 3 Department of Rehabilitation Medicine, Methods: Patients were referred to hospital for investigations and rehabilitation Danderyd University Hospital, Stockholm, Sweden because of a suspected diagnosis of myalgic encephalomyelitis/chronic fatigue syn- drome (ME/CFS). The criteria for further referral to full-night polysomnography 4 Department of Medical and Health Sciences, Faculty of Medicine and Health (PSG) were symptoms of excessive daytime sleepiness and/or tiredness in the Sciences, Linkoping€ University, Pain and questionnaires. Rehabilitation Centre, Anaesthetics, Results: Of a total of 381 patients, 78 (20.5%) patients underwent PSG: 66 women Operations and Specialty Surgery Centre, and 12 men, mean age 48.6 years, standard deviation 69.9 years. On the basis of the Region Ostergotland,€ Linkoping,€ Sweden PSG, 31 (40.3%) patients were diagnosed with obstructive sleep apnoea, 7 (8.9%) 5 Department of Clinical Science, patients with periodic limb movement disorder, 32 (41.0%) patients with restless legs Intervention and Technology (CLINTEC), Division of Otorhinolaryngology, syndrome and 54 (69.3%) patients had one or more other sleep disorder. All patients Karolinska University Hospital, were grouped into those who fulfilled the diagnostic criteria for ME/CFS (n 5 55, Stockholm, Sweden 70.5%) and those who did not (n 5 23, 29.5%). The latter group had significantly higher respiratory (P 5 .01) and total arousal (P 5 .009) indexes and a higher oxy- Correspondence gen desaturation index (P 5 .009). Evelina Pajediene, MD, Resident in Neurology, Department of Neurology, Conclusions: More than half of these chronic fatigue patients, who also have exces- Kaunas Clinics, Hospital of Lithuanian sive daytime sleepiness and/or tiredness, were diagnosed with sleep disorders such as University of Health Sciences, Eiveniu St 2, obstructive sleep apnoea, periodic limb movement disorder and/or restless legs syn- Kaunas 50009, Lithuania. drome. Patients with such complaints should undergo polysomnography, fill in Email: [email protected] questionnaires and be offered treatment for sleep disorders before the diagnose ME/ CFS is set. KEYWORDS chronic fatigue syndrome, fatigue, myalgic encephalomyelitis, polysomnography, sleep, sleep apnoea 1 | INTRODUCTION Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by physical and mental fatigue Many patients who consult doctors from a variety of medical and fatigability that are not ameliorated by rest. In addi- specialties complain about feeling tired, sleepy or fatigued, tion, patients suffer from widespread diffuse pain and cog- which is causing a significant economic burden at both the nitive difficulties that last more than 6 months.2 Patients individual and societal level.1 The process of diagnosing a often report malaise, worsening of symptoms with effort, fatigued patient should begin with clearly defining the symp- non-restorative sleep, sore throat, swollen lymph nodes toms, before proceeding to the exclusion of sleep-related and and other symptoms.3 Depending on the criteria used, the psychosomatic comorbidities. prevalence varies from 1.2%, when the more strict Clin Respir J. 2018;12:1389–1397. wileyonlinelibrary.com/journal/crj VC 2017 John Wiley & Sons Ltd | 1389 1390 | PAJEDIENE ET AL. Canadian criteria are applied, to 2.6%, when the broad accordance with the Centers for Disease Control2 and/or Oxford criteria are used.4 Canadian criteria3 following medical, psychological, labora- Even though in all available case definition guidelines of tory results, brain imaging and PSG investigation/treatment CFS, sleep problems are described as a minor criterion,5 the of OSA. exact definition of sleep disturbance is not clear. According Our inclusion criteria for performing PSG for all consec- to a phone survey-based study by Unger et al, one of the utively referred patients were symptoms of excessive day- most prevalent complaints among patients diagnosed with time sleepiness, by using Epworth sleepiness scale 10, and/ CFS is unrefreshing sleep; however, this study did not find or often or always tired during mornings and/or daytime, any increased association between subjectively expressed from specific questionnaires (see below). In-lab, full-night chronic fatigue and excessive daytime sleepiness or obstruc- PSG was performed at the Department of Otorhinolaryngol- tive sleep apnea (OSA).6 According to several studies, the ogy (ORL), Karolinska University Hospital (see below). undiagnosed primary sleep disorder was detected in 0–50% Afterward, the results of PSG and all related sleep com- of chronically fatigued patients.7,8 Through a detailed diag- plaints were processed by a specialist in sleep medicine nostic investigation with questionnaires, polysomnography (DF). (PSG) and multiple sleep latency testing, Mariman et al Following these evaluations, including PSG, all patients found that 49.8% of patients diagnosed with ME/CFS were were divided into two groups: those diagnosed with ME/ suffering from predominant or co-morbid sleep disorders and CFS (the ME/CFS group) and those diagnosed with other that 28.7% had OSA.9 A PSG-based controlled study by Neu disorders (the non-ME/CFS group). The group of non-ME/ et al detected more slow-wave sleep and microarousals in 16 CFS patients did not fulfil the symptom-based criteria for CFS patients, but also lower grip strength and reduced con- ME/CFS or had exclusionary conditions, such as psychiatric centrations of circulating cytokines. However, the group did disorders (untreated burn-out syndrome, depression and/or not find OSA or periodic limb movement disorder anxiety) often together with pain syndrome, or a suspected (PLMD).10 exclusionary or untreated somatic disorder that could explain In the present study, we hypothesized that chronically the symptoms. The strict exclusionary criteria regarding obe- fatigued patients with excessive daytime sleepiness and/or sity and drug abuse were applied before accepting a referral tiredness suffer from treatable sleep-related disorders such as because of official referring guidelines. Referrals were dis- cussed by two CFS-specialists before approval. OSA, PLMD and restless legs syndrome (RLS), which could If a diagnosis of OSA and/or PLMD was revealed on the be detected by using PSG and specific questionnaires. basis of the PSG, the patient was offered treatment and follow-up. Patients with mild sleep disturbances were pro- 2 | MATERIALS AND METHODS vided with treatment recommendations through their primary care clinic, while those with moderate-to-severe OSA were 2.1 | Participants followed-up by the sleep specialist (DF). If PLMD and/or The participants were consecutive patients who entered the RLS were diagnosed, the patients were referred to a neurolo- gist. However, the results of treatment are not presented, as ME/CFS project at Danderyd University Hospital, Stock- treatment outcomes were not within the scope of this study. holm in the period from 2011 to 2013. The unit in Danderyd University Hospital served as a public healthcare tertiary clinic for patients with chronic fatigue. The majority of 2.2 | Questionnaires patients were referred from primary health care clinics and — psychiatry and neurology departments within Stockholm 1. The Epworth Sleepiness Scale (ESS) aself-administered ’ County. questionnaire measuring the subject s general level of day- 11 A clinician, who was a specialist in rehabilitation medi- time sleepiness. cine or neurology, screened every patient over the course of 2. The ORL department’s local self-reported sleep question- a 90-minute consultation. Investigations with laboratory tests naire consisting of six questions about OSA symptoms were performed in order to exclude ongoing inflammation, such as snoring, breathing pauses during sleep, sleepiness infection, metabolic and immunological disorders and/or while driving and morning and daytime tiredness. There other pathological conditions. In a majority of patients, brain were also five questions concerning insomnia-related com- magnetic resonance imaging was performed in order to plaints. A four-grade Likert scale with the alternatives exclude brain disorders. In addition, patients met a certified never, sometimes, often, or always was used. psychologist for 90 minutes of psychological evaluation 3. A validated questionnaire concerning RLS with four posi- including a standardized psychiatric interview and neuropsy- tive responses being mandatory for the diagnosis of chological testing. The diagnosis of ME/CFS was made in RLS.12 PAJEDIENE ET AL. | 1391 4. A validated question concerning self-rated health with five qualitative variables and by means and standard deviations options, from ‘excellent’ to ‘very poor’.13 for quantitative variables. 5. The Swedish version of the Multidimensional Fatigue The ME/CFS group and the non-ME/CFS group were Inventory